JP6586863B2 - Method for producing compound having 3-oxabicyclo [3.3.0] octane skeleton, said compound, intermediate of said compound, sex stimulant of king beetle, and control agent for singing beetle - Google Patents

Method for producing compound having 3-oxabicyclo [3.3.0] octane skeleton, said compound, intermediate of said compound, sex stimulant of king beetle, and control agent for singing beetle Download PDF

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JP6586863B2
JP6586863B2 JP2015227736A JP2015227736A JP6586863B2 JP 6586863 B2 JP6586863 B2 JP 6586863B2 JP 2015227736 A JP2015227736 A JP 2015227736A JP 2015227736 A JP2015227736 A JP 2015227736A JP 6586863 B2 JP6586863 B2 JP 6586863B2
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鈴木　敏夫
敏夫 鈴木
久大 萩原
久大 萩原
拓恵 内田
拓恵 内田
直 辻井
直 辻井
裕嗣 小野
裕嗣 小野
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Niigata University
National Agriculture and Food Research Organization
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本発明は、３−オキサビシクロ［３．３．０］オクタン骨格を有する化合物の製造方法、前記化合物、前記化合物の中間体、ゴマダラカミキリの性刺激剤、及びゴマダラカミキリの防除剤に関する。   The present invention relates to a method for producing a compound having a 3-oxabicyclo [3.3.0] octane skeleton, the above compound, an intermediate of the above compound, a sex stimulant for the longhorn beetle, and a control agent for the longhorn beetle.

ゴマダラカミキリは、柑橘類など多種の本木植物に対する大害虫である。成虫の移動性が高く、産卵が樹皮下になされ、幼虫は幹内部を食害するため、殺虫剤による効率的な駆除が困難である。そこで性フェロモンを利用した防除剤の実用化が求められている。   The long-horned beetle is a great pest for a variety of main plants such as citrus fruits. Since adults have high mobility, egg laying is done under the tree, and larvae damage the inside of the trunk, so it is difficult to effectively control with insecticides. Therefore, practical application of a control agent using sex pheromone is required.

ゴマダラカミキリの雌性フェロモンの成分を検索した結果、炭化水素群（例えば、特許文献１参照）、ケトン群（例えば、特許文献２参照）、及び３−オキサビシクロ［３．３．０］オクタン骨格を有する化合物群（例えば、特許文献３、非特許文献１及び２参照）が同定され、これらの３つの化合物群を混合した場合に、最も強い性刺激活性があることが判明している（例えば、特許文献２参照）。   As a result of searching for a female pheromone component of the longhorn beetle, it has a hydrocarbon group (for example, see Patent Document 1), a ketone group (for example, see Patent Document 2), and a 3-oxabicyclo [3.3.0] octane skeleton. Compound groups (see, for example, Patent Document 3 and Non-Patent Documents 1 and 2) have been identified, and when these three compound groups are mixed, it has been found that they have the strongest sexual stimulating activity (for example, patents). Reference 2).

上記３つの化合物群のうち、炭化水素群の主要な８つの成分、及びケトン群の４つの成分は、化学合成により容易かつ大量に提供することができ、化学合成した化合物を用いた場合でも雌由来の成分と同等の性刺激活性が得られることが示されている。
しかし、炭化水素群とケトン群の成分に比べ、３−オキサビシクロ［３．３．０］オクタン骨格を有する化合物群の化学合成は、多数の不斉炭素をもつ骨格の合成例だけでなく、天然からの単離も他に全く知られていないため、容易ではない。したがって、３−オキサビシクロ［３．３．０］オクタン骨格を有するリード化合物から同等以上の活性を有し、より簡便に化学合成できる新規化合物の発明、及びその合成法の確立が望まれていた。 Of the above three compound groups, the eight main components of the hydrocarbon group and the four components of the ketone group can be provided easily and in large quantities by chemical synthesis, and even when chemically synthesized compounds are used, It has been shown that sexual stimulation activity equivalent to the component derived from can be obtained.
However, the chemical synthesis of compounds having a 3-oxabicyclo [3.3.0] octane skeleton is not only a synthesis example of a skeleton having a large number of asymmetric carbons, compared to the components of the hydrocarbon group and the ketone group, Isolation from nature is not easy because no other is known. Accordingly, there has been a demand for the invention of a novel compound having a comparable or higher activity from a lead compound having a 3-oxabicyclo [3.3.0] octane skeleton and capable of chemical synthesis more easily, and establishment of the synthesis method thereof. .

特開平１１−８００３９号公報Japanese Patent Laid-Open No. 11-80039 特許第４０２３７２１号公報Japanese Patent No. 4023721 特許第４６２１９０４号公報Japanese Patent No. 4621904

Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ，４８（１３），２３９５−２４００（２００７）Tetrahedron Letters, 48 (13), 2395-2400 (2007) Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ，４８（３２），５６０９−５６１１（２００７）Tetrahedron Letters, 48 (32), 5609-5611 (2007)

本発明は、前記従来における諸問題を解決し、以下の目的を達成することを課題とする。即ち、本発明は、３−オキサビシクロ［３．３．０］オクタン骨格を有するリード化合物からより簡便に化学合成可能な３−オキサビシクロ［３．３．０］オクタン骨格を有する化合物の製造方法、前記化合物、前記化合物の中間体、ゴマダラカミキリの性刺激剤、及びゴマダラカミキリの防除剤を提供することを目的とする。   An object of the present invention is to solve the conventional problems and achieve the following objects. That is, the present invention provides a method for producing a compound having a 3-oxabicyclo [3.3.0] octane skeleton that can be more easily chemically synthesized from a lead compound having a 3-oxabicyclo [3.3.0] octane skeleton. It is an object of the present invention to provide a compound, an intermediate of the compound, a sex stimulant for the long-horned beetle, and a control agent for the long-horned beetle.

本発明者らは、前記目的を解決すべく、鋭意検討した結果、３−オキサビシクロ［３．３．０］オクタン骨格を有する新規化合物を化学合成することに成功し、それらがゴマダラカミキリに対する優れた性刺激活性を有することを見出し、本発明を完成するに至った。   As a result of intensive studies to solve the above-mentioned object, the present inventors have succeeded in chemically synthesizing novel compounds having a 3-oxabicyclo [3.3.0] octane skeleton, which are superior to the longhorn beetle. It has been found that it has sex stimulating activity, and the present invention has been completed.

本発明は、本発明者らによる前記知見に基づくものであり、前記課題を解決するための手段としては、以下の通りである。即ち、
＜１＞ 下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基をアルデヒド基に置換し、下記構造式２７で表される化合物を生成させる工程と、
前記構造式２７で表される化合物のアルデヒド基を順次反応させて２−メチル−５−ヒドロキシ−１−ペンテニル基に置換し、下記構造式３１で表される化合物を生成させる工程と、
前記構造式３１で表される化合物の２−メチル−５−ヒドロキシ−１−ペンテニル基を環化し、トリメチルシリル基を水酸基に置換し、下記構造式１で表される化合物を生成させる工程と、を含むことを特徴とする下記構造式１で表される化合物の製造方法である。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、２５、２７及び３１中、ＴＭＳはトリメチルシリルを表す。）
＜２＞ 下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基を順次反応させてアセチル基に置換し、下記構造式２で表される化合物を生成させる工程と、を含むことを特徴とする下記構造式２で表される化合物の製造方法である。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、及び２５中、ＴＭＳはトリメチルシリルを表す。）
＜３＞ 下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基をアルデヒド基に置換し、下記構造式２７で表される化合物を生成させる工程と、
前記構造式２７で表される化合物のアルデヒド基を順次反応させて２−メチル−５−ヒドロキシ−１−ペンテニル基に置換し、下記構造式３１で表される化合物を生成させる工程と、
前記構造式３１で表される化合物のトリメチルシリル基を水酸基に置換し、下記構造式３で表される化合物を生成させる工程と、を含むことを特徴とする下記構造式３で表される化合物の製造方法である。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、２５、２７及び３１中、ＴＭＳはトリメチルシリルを表す。）
＜４＞ 下記構造式１で表されることを特徴とする化合物である。
〔構造式１〕
＜５＞ 下記構造式２で表されることを特徴とする化合物である。
〔構造式２〕
＜６＞ 下記構造式３で表されることを特徴とする化合物である。
〔構造式３〕
＜７＞ 下記構造式２２〜３３のいずれかで表される前記＜４＞から＜６＞のいずれかに記載の化合物の中間体である。
＜８＞ 前記＜４＞から＜６＞のいずれかに記載の化合物を有効成分として含むことを特徴とするゴマダラカミキリの性刺激剤である。
＜９＞ ヘプタコサン、ノナコサン、４−メチルヘキサコサン、４−メチルオクタコサン、９−メチルヘプタコサン、９−メチルノナコサン、１５−メチルヘントリアコンタン、及び１５−メチルヘントリトリアコンタンからなる群から選ばれる少なくとも１種の炭化水素を更に含む前記＜８＞に記載のゴマダラカミキリの性刺激剤である。
＜１０＞ ヘプタコサン−１０−オン、（１８Ｚ）−ヘプタコセン−１０−オン、及び（１８Ｚ，２１Ｚ）−ヘプタコサジエン−１０−オンからなる群から選ばれる少なくとも１種のケトンを更に含む前記＜８＞から＜９＞のいずれかに記載のゴマダラカミキリの性刺激剤である。
＜１１＞ 基材に塗布又は含浸されてなる前記＜８＞から＜１０＞のいずれかに記載のゴマダラカミキリの性刺激剤である。
＜１２＞ 前記＜８＞から＜１１＞のいずれかに記載のゴマダラカミキリの性刺激剤を含むことを特徴とするゴマダラカミキリの防除剤である。
＜１３＞ 殺虫成分を更に含む前記＜１２＞に記載のゴマダラカミキリの防除剤である。 The present invention is based on the above findings by the present inventors, and means for solving the above problems are as follows. That is,
<1> By substituting the compound represented by the following structural formula 21b with hydrogen in the presence of a catalyst, substituting the 4-methoxyphenylmethyl group with a trichloroacetyl group, and protecting the hydroxyl group at the 5-position with a trimethylsilyl group, Generating a compound represented by Structural Formula 24;
Adding an oxo group to the 2-position of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25;
Replacing the trichloroacetyl group of the compound represented by the structural formula 25 with an aldehyde group to form a compound represented by the following structural formula 27;
A step of sequentially reacting an aldehyde group of the compound represented by the structural formula 27 and substituting it with a 2-methyl-5-hydroxy-1-pentenyl group to form a compound represented by the following structural formula 31;
Cyclizing the 2-methyl-5-hydroxy-1-pentenyl group of the compound represented by Structural Formula 31 and substituting the trimethylsilyl group with a hydroxyl group to form a compound represented by Structural Formula 1 below. It is a manufacturing method of the compound represented by following Structural formula 1 characterized by including.
(However, in Structural Formula 21b, MPM represents 4-methoxyphenylmethyl, and in Structural Formulas 24, 25, 27, and 31, TMS represents trimethylsilyl.)
<2> By substituting the compound represented by the following structural formula 21b with hydrogen in the presence of a catalyst, substituting the 4-methoxyphenylmethyl group with a trichloroacetyl group, and protecting the hydroxyl group at the 5-position with a trimethylsilyl group, Generating a compound represented by Structural Formula 24;
Adding an oxo group to the 2-position of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25;
A step of sequentially reacting the trichloroacetyl group of the compound represented by the structural formula 25 to substitute an acetyl group to form a compound represented by the following structural formula 2; It is a manufacturing method of the compound represented by these.
(However, in Structural Formula 21b, MPM represents 4-methoxyphenylmethyl, and in Structural Formulas 24 and 25, TMS represents trimethylsilyl.)
<3> By substituting the compound represented by the following structural formula 21b with hydrogen in the presence of a catalyst, substituting the 4-methoxyphenylmethyl group with a trichloroacetyl group, and protecting the hydroxyl group at the 5-position with a trimethylsilyl group, Generating a compound represented by Structural Formula 24;
Adding an oxo group to the 2-position of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25;
Replacing the trichloroacetyl group of the compound represented by the structural formula 25 with an aldehyde group to form a compound represented by the following structural formula 27;
A step of sequentially reacting an aldehyde group of the compound represented by the structural formula 27 and substituting it with a 2-methyl-5-hydroxy-1-pentenyl group to form a compound represented by the following structural formula 31;
Substituting the trimethylsilyl group of the compound represented by Structural Formula 31 with a hydroxyl group to form a compound represented by Structural Formula 3 below, It is a manufacturing method.
(However, in Structural Formula 21b, MPM represents 4-methoxyphenylmethyl, and in Structural Formulas 24, 25, 27, and 31, TMS represents trimethylsilyl.)
<4> A compound represented by the following structural formula 1.
[Structural formula 1]
<5> A compound represented by the following structural formula 2.
[Structural formula 2]
<6> A compound represented by the following structural formula 3.
[Structural formula 3]
<7> An intermediate of the compound according to any one of <4> to <6>, which is represented by any one of the following structural formulas 22 to 33.
<8> A sex stimulant for longhorn beetle, comprising the compound according to any one of <4> to <6> as an active ingredient.
<9> From the group consisting of heptacosan, nonacosane, 4-methylhexacosane, 4-methyloctacosane, 9-methylheptacosane, 9-methylnonacosane, 15-methylhentriacontane, and 15-methylhentriatritan The sex stimulant for longhorn beetle according to <8>, further including at least one selected hydrocarbon.
<10> From the above <8> further comprising at least one kind of ketone selected from the group consisting of heptacosane-10-one, (18Z) -heptacosen-10-one, and (18Z, 21Z) -heptacosadien-10-one <9> The sexual stimulant for longhorn beetle according to any one of <9>.
<11> The sex stimulant for longhorn beetle according to any one of <8> to <10>, which is applied or impregnated on a base material.
<12> A control agent for a long-horned beetle characterized by including the sex stimulant for long-horned beetle according to any one of <8> to <11>.
<13> The agent for controlling longhorn beetle according to <12>, further including an insecticidal component.

本発明によれば、従来における前記諸問題を解決し、前記目的を達成することができ、３−オキサビシクロ［３．３．０］オクタン骨格を有するリード化合物からより簡便に化学合成可能な３−オキサビシクロ［３．３．０］オクタン骨格を有する化合物の製造方法、前記化合物、前記化合物の中間体、ゴマダラカミキリの性刺激剤、及びゴマダラカミキリの防除剤を提供することができる。   According to the present invention, the above-mentioned problems can be solved and the object can be achieved, and chemical synthesis can be more easily performed from a lead compound having a 3-oxabicyclo [3.3.0] octane skeleton. -The manufacturing method of the compound which has oxabicyclo [3.3.0] octane frame | skeleton, the said compound, the intermediate body of the said compound, the sex stimulant of a Japanese pearl beetle, and the control agent of a Japanese common pearl beetle can be provided.

（化合物の製造方法）
本発明の化合物の製造方法は、下記構造式１で表される化合物（以下、「化合物１」と称することがある）の製造方法であって、
下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基をアルデヒド基に置換し、下記構造式２７で表される化合物を生成させる工程と、
前記構造式２７で表される化合物のアルデヒド基を順次反応させて２−メチル−５−ヒドロキシ−１−ペンテニル基に置換し、下記構造式３１で表される化合物を生成させる工程と、
前記構造式３１で表される化合物の２−メチル−５−ヒドロキシ−１−ペンテニル基を環化し、トリメチルシリル基を水酸基に置換し、前記構造式１で表される化合物を生成させる工程と、を含み、更に必要に応じて精製工程などのその他の工程を含む。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、２５、２７及び３１中、ＴＭＳはトリメチルシリルを表す。） (Method for producing compound)
The method for producing a compound of the present invention is a method for producing a compound represented by the following structural formula 1 (hereinafter sometimes referred to as “compound 1”),
The compound represented by the following structural formula 21b was replaced with hydrogen in the presence of a catalyst, the 4-methoxyphenylmethyl group was replaced with a trichloroacetyl group, and the hydroxyl group at the 5-position was protected with a trimethylsilyl group, whereby the following structural formula 24 A step of producing a compound represented by:
Adding an oxo group to the 2-position of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25;
Replacing the trichloroacetyl group of the compound represented by the structural formula 25 with an aldehyde group to form a compound represented by the following structural formula 27;
A step of sequentially reacting an aldehyde group of the compound represented by the structural formula 27 and substituting it with a 2-methyl-5-hydroxy-1-pentenyl group to form a compound represented by the following structural formula 31;
Cyclizing the 2-methyl-5-hydroxy-1-pentenyl group of the compound represented by Structural Formula 31 and substituting the trimethylsilyl group with a hydroxyl group to produce the compound represented by Structural Formula 1. And other steps such as a purification step as necessary.
(However, in Structural Formula 21b, MPM represents 4-methoxyphenylmethyl, and in Structural Formulas 24, 25, 27, and 31, TMS represents trimethylsilyl.)

また、本発明の化合物の製造方法は、下記構造式２で表される化合物（以下、「化合物２」と称することがある）の製造方法であって、
下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基を順次反応させてアセチル基に置換し、前記構造式２で表される化合物を生成させる工程と、を含み、更に必要に応じて精製工程などのその他の工程を含む。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、及び２５中、ＴＭＳはトリメチルシリルを表す。） The method for producing the compound of the present invention is a method for producing a compound represented by the following structural formula 2 (hereinafter sometimes referred to as “compound 2”),
The compound represented by the following structural formula 21b was replaced with hydrogen in the presence of a catalyst, the 4-methoxyphenylmethyl group was replaced with a trichloroacetyl group, and the hydroxyl group at the 5-position was protected with a trimethylsilyl group, whereby the following structural formula 24 A step of producing a compound represented by:
Adding an oxo group to the 2-position of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25;
A step of sequentially reacting the trichloroacetyl group of the compound represented by the structural formula 25 and substituting the acetyl group to form a compound represented by the structural formula 2, and further purifying as necessary. Including other processes.
(However, in Structural Formula 21b, MPM represents 4-methoxyphenylmethyl, and in Structural Formulas 24 and 25, TMS represents trimethylsilyl.)

また、本発明の化合物の製造方法は、下記構造式３で表される化合物（以下、「化合物３」と称することがある）の製造方法であって、
下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基をアルデヒド基に置換し、下記構造式２７で表される化合物を生成させる工程と、
前記構造式２７で表される化合物のアルデヒド基を順次反応させて２−メチル−５−ヒドロキシ−１−ペンテニル基に置換し、下記構造式３１で表される化合物を生成させる工程と、
前記構造式３１で表される化合物のトリメチルシリル基を水酸基に置換し、前記構造式３で表される化合物を生成させる工程と、を含み、更に必要に応じて精製工程などのその他の工程を含む。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、２５、２７及び３１中、ＴＭＳはトリメチルシリルを表す。） The method for producing the compound of the present invention is a method for producing a compound represented by the following structural formula 3 (hereinafter sometimes referred to as “compound 3”),
The compound represented by the following structural formula 21b was replaced with hydrogen in the presence of a catalyst, the 4-methoxyphenylmethyl group was replaced with a trichloroacetyl group, and the hydroxyl group at the 5-position was protected with a trimethylsilyl group, whereby the following structural formula 24 A step of producing a compound represented by:
Adding an oxo group to the 2-position of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25;
Replacing the trichloroacetyl group of the compound represented by the structural formula 25 with an aldehyde group to form a compound represented by the following structural formula 27;
A step of sequentially reacting an aldehyde group of the compound represented by the structural formula 27 and substituting it with a 2-methyl-5-hydroxy-1-pentenyl group to form a compound represented by the following structural formula 31;
Substituting the trimethylsilyl group of the compound represented by the structural formula 31 with a hydroxyl group to form the compound represented by the structural formula 3, and further including other steps such as a purification step if necessary. .
(However, in Structural Formula 21b, MPM represents 4-methoxyphenylmethyl, and in Structural Formulas 24, 25, 27, and 31, TMS represents trimethylsilyl.)

（化合物）
本発明の化合物は、下記構造式１〜３のいずれかで表される３−オキサビシクロ［３．３．０］オクタン骨格を有する化合物（化合物１〜３）である。
前記化合物１は、本発明の化合物１の製造方法により、好適に製造することができる。
前記化合物２は、本発明の化合物２の製造方法により、好適に製造することができる。
前記化合物３は、本発明の化合物３の製造方法により、好適に製造することができる。
〔構造式１〕
〔構造式２〕
〔構造式３〕
(Compound)
The compound of the present invention is a compound (compounds 1 to 3) having a 3-oxabicyclo [3.3.0] octane skeleton represented by any of the following structural formulas 1 to 3.
The said compound 1 can be suitably manufactured with the manufacturing method of the compound 1 of this invention.
The said compound 2 can be suitably manufactured with the manufacturing method of the compound 2 of this invention.
The said compound 3 can be suitably manufactured with the manufacturing method of the compound 3 of this invention.
[Structural formula 1]
[Structural formula 2]
[Structural formula 3]

これまでに、３−オキサビシクロ［３．３．０］オクタン骨格を有する化合物群として、下記構造式４、５及び６のいずれかで表される化合物（以下、「化合物４、５及び６」と称することがある。）が、ゴマダラカミキリから単離され、化学構造について絶対配置が決定されている（Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ，４８（３２），５６０９−５６１１（２００７）参照）。
化合物６は、本発明の化合物３のジアステレオマーであり、したがって、化合物３及び化合物６の物理化学的性質及び生物学的作用は、互いに異なる。 Until now, as a compound group having a 3-oxabicyclo [3.3.0] octane skeleton, compounds represented by any one of the following structural formulas 4, 5 and 6 (hereinafter referred to as “compounds 4, 5 and 6”) Have been isolated from the long-horned beetle, and the absolute configuration of the chemical structure has been determined (see Tetrahedron Letters, 48 (32), 5609-5611 (2007)).
Compound 6 is a diastereomer of Compound 3 of the present invention, and thus the physicochemical properties and biological actions of Compound 3 and Compound 6 are different from each other.

なお、文献「Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ，４８（３２），５６０９−５６１１（２００７）」において絶対配置が決定された化合物４、５及び６については、まず、特許第４６２１９０４号公報にて単離同定が報告され、次いで、文献「Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔｅｒｓ，４８（１３），２３９５−２４００（２００７）」にて構造決定がなされ、それぞれゴマダラクトンＡ、Ｂ、及びＣと命名された。そのため、特許第４６２１９０４号公報には、化合物４〜６とは３−オキサビシクロ［３．３．０］オクタン骨格上の一部炭素が異なる（即ち、化合物４〜６とジアステレオマー又は鏡像体の関係にある）絶対配置を有する化合物が記載されているものの、特許第４６２１９０４号公報に記載の化合物は、化合物４〜６と同じスペクトルを有するため、前記構造式４〜６のいずれかで表される化合物（化合物４〜６）の立体配置を有するものと解釈される。   Regarding compounds 4, 5 and 6 whose absolute configuration was determined in the document “Tetrahedron Letters, 48 (32), 5609-5611 (2007)”, first, isolation and identification were reported in Japanese Patent No. 4621904. Subsequently, the structure was determined in the document “Tetrahedron Letters, 48 (13), 2395-2400 (2007)” and named sesame lactones A, B, and C, respectively. Therefore, in Japanese Patent No. 4621904, compounds 4 to 6 are different in carbon on the 3-oxabicyclo [3.3.0] octane skeleton (that is, compounds 4 to 6 and diastereomers or enantiomers). However, since the compound described in Japanese Patent No. 4621904 has the same spectrum as the compounds 4 to 6, the compound represented by any one of the structural formulas 4 to 6 is described. It is interpreted that it has the configuration of the compound (compounds 4 to 6).

（中間体）
本発明の中間体は、下記構造式２２〜３３のいずれかで表される本発明の化合物４〜６の中間体である。
前記中間体は、本発明の化合物１〜３の製造方法における中間体である。
また、前記中間体は、本発明の化合物１〜３以外の、新たな３−オキサビシクロ［３．３．０］オクタン骨格を有する化合物を合成する際のリード化合物として有用である。
(Intermediate)
The intermediate of the present invention is an intermediate of compounds 4 to 6 of the present invention represented by any of the following structural formulas 22 to 33.
The said intermediate body is an intermediate body in the manufacturing method of the compounds 1-3 of this invention.
The intermediate is useful as a lead compound in the synthesis of a compound having a new 3-oxabicyclo [3.3.0] octane skeleton other than the compounds 1 to 3 of the present invention.

（ゴマダラカミキリの性刺激剤）
本発明のゴマダラカミキリの性刺激剤は、本発明の化合物を有効成分として含み、その他の性刺激剤を含むことが好ましく、更に必要に応じてその他の成分を含む。 (Sexually stimulating agent for longhorn beetle)
The sex stimulant of the long-horned beetle of the present invention contains the compound of the present invention as an active ingredient, preferably contains other sex stimulants, and further contains other ingredients as necessary.

＜その他の性刺激剤＞
前記その他の性刺激剤としては、ゴマダラカミキリに対する性刺激作用を有する化合物であれば特に制限はなく、目的に応じて適宜選択することができ、例えば、炭化水素、ケトンなどが挙げられる。これらは１種単独で使用してもよいし、２種以上を併用してもよい。
前記炭化水素としては、例えば、ヘプタコサン、ノナコサン、４−メチルヘキサコサン、４−メチルオクタコサン、９−メチルヘプタコサン、９−メチルノナコサン、１５−メチルヘントリアコンタン、１５−メチルヘントリトリアコンタンなどが挙げられる。これらは１種単独で使用してもよいし、２種以上を併用してもよい。
前記ケトンとしては、例えば、ヘプタコサン−１０−オン、（１８Ｚ）−ヘプタコセン−１０−オン、（１８Ｚ，２１Ｚ）−ヘプタコサジエン−１０−オンなどが挙げられる。これらは１種単独で使用してもよいし、２種以上を併用してもよい。 <Other sex stimulants>
The other sexual stimulant is not particularly limited as long as it is a compound having a sexual stimulating action against a long-horned beetle, and can be appropriately selected according to the purpose. Examples thereof include hydrocarbons and ketones. These may be used individually by 1 type and may use 2 or more types together.
Examples of the hydrocarbon include heptacosane, nonacosane, 4-methylhexacosane, 4-methyloctacosane, 9-methylheptacosane, 9-methylnonacosane, 15-methylhentriacontane, 15-methylhentriatritan. Etc. These may be used individually by 1 type and may use 2 or more types together.
Examples of the ketone include heptacosane-10-one, (18Z) -heptacosen-10-one, and (18Z, 21Z) -heptacosadien-10-one. These may be used individually by 1 type and may use 2 or more types together.

＜その他の成分＞
前記その他の成分としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、溶媒、担体、徐放剤などが挙げられる。
前記溶媒としては、例えば、ｎ−ヘキサン、酢酸エチル、メタノール、エタノールなどが挙げられる。
前記担体としては、例えば、プラスチック、不織布、ゴムセプタムなどが挙げられる。
前記徐放剤としては、例えば、ゲル状物質、多孔質物質、樹脂などが挙げられる。 <Other ingredients>
There is no restriction | limiting in particular as said other component, According to the objective, it can select suitably, For example, a solvent, a carrier, a sustained release agent, etc. are mentioned.
Examples of the solvent include n-hexane, ethyl acetate, methanol, ethanol and the like.
Examples of the carrier include plastic, non-woven fabric, and rubber septum.
Examples of the sustained release agent include a gel material, a porous material, and a resin.

前記ゴマダラカミキリの性刺激剤は、基材に塗布又は含浸されてなることが好ましい。
前記ゴマダラカミキリの性刺激剤が、前記基材に塗布されてなる場合、前記基材としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、ゼラチンカプセル、ガラス片、金属片、プラスチック片などが挙げられる。
前記基材の大きさとしては、ゴマダラカミキリの雌個体程度の大きさであれば特に制限はなく、目的に応じて適宜選択することができるが、長さ２０ｍｍ〜４０ｍｍ（例えば、３５ｍｍ）、幅５ｍｍ〜１５ｍｍ（例えば、１２ｍｍ）、高さ５ｍｍ〜１５ｍｍ（例えば、１２ｍｍ）が好ましい。
前記基材の形状としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、円筒状、角柱状、球状、楕円球状などが挙げられる。
前記塗布は、ゴマダラカミキリの成虫雄が接触可能な状態に塗布されることが好ましい。 It is preferable that the sex stimulant for the longhorn beetle is applied or impregnated on a base material.
In the case where the sex stimulant for the longhorn beetle is applied to the substrate, the substrate is not particularly limited and may be appropriately selected depending on the intended purpose. For example, gelatin capsules, glass pieces, metal pieces And plastic pieces.
The size of the base material is not particularly limited as long as it is about the size of a female beetle, and can be appropriately selected according to the purpose. However, the length is 20 mm to 40 mm (for example, 35 mm), and the width is 5 mm. -15 mm (for example, 12 mm) and a height of 5 mm to 15 mm (for example, 12 mm) are preferable.
There is no restriction | limiting in particular as a shape of the said base material, According to the objective, it can select suitably, For example, cylindrical shape, prismatic shape, spherical shape, elliptical spherical shape etc. are mentioned.
It is preferable that the coating is performed in such a manner that an adult male of a long-horned beetle can be contacted.

前記ゴマダラカミキリの性刺激剤の塗布量としては、特に制限はなく、目的に応じて適宜選択できるが、１雌相当量の塗布量であっても前記性刺激活性を示すため、前記基材当たりの前記構造式１〜３のいずれかで表される化合物の量で、０．５μｇ〜２５μｇが好ましく、１μｇ〜１０μｇがより好ましい。   The application amount of the sex stimulant for the longhorn beetle is not particularly limited and can be appropriately selected according to the purpose. The amount of the compound represented by any one of the structural formulas 1 to 3 is preferably 0.5 μg to 25 μg, and more preferably 1 μg to 10 μg.

前記ゴマダラカミキリの性刺激剤が、前記基材に含浸されてなる場合、前記基材としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、不撚布、スポンジ状物体などが挙げられる。
この場合、前記溶媒に溶解した前記ゴマダラカミキリの性刺激剤が含浸されることが好ましい。
前記ゴマダラカミキリの性刺激剤の含有量としては、特に制限はなく、目的に応じて適宜選択できるが、前記基材の表面積あたりの前記溶媒に対する前記構造式１〜３のいずれかで表される化合物の含有量で、０．５μg／ｃｍ２〜２０μg／ｃｍ２が好ましく、１μg／ｃｍ２〜１０μg／ｃｍ２がより好ましく、前記基材の体積あたりの前記溶媒に対する前記構造式１〜３のいずれかで表される化合物の含有量で、５０μg／ｃｍ３〜１０００μg／ｃｍ３が好ましく、１００μg／ｃｍ３〜２００μg／ｃｍ３がより好ましい。 When the base material is impregnated with the sex stimulant of the longhorn beetle, the base material is not particularly limited and can be appropriately selected according to the purpose. For example, untwisted cloth, sponge-like object, etc. Is mentioned.
In this case, it is preferable to impregnate the sex stimulant of the longhorn beetle dissolved in the solvent.
There is no restriction | limiting in particular as content of the sex stimulant of the long-horned beetle, Although it can select suitably according to the objective, The compound represented by either of the said Structural formula 1-3 with respect to the said solvent per surface area of the said base material in content, preferably 0.5μg / cm 2 ~20μg / cm 2 , more preferably 1μg / cm 2 ~10μg / cm 2 , any of the structural formula 1-3 with respect to the solvent per volume of the substrate in content of the compound represented by either preferably 50μg / cm 3 ~1000μg / cm 3 , 100μg / cm 3 ~200μg / cm 3 is more preferable.

本発明のゴマダラカミキリの性刺激剤に、ゴマダラカミキリの雄がふ節や触角などで接触した場合、前記ゴマダラカミキリの性刺激剤を塗布した前記基材の表面や、近辺に存在する他のゴマダラカミキリの雄に対し、刺激活性を示すと共に、それを抱き込みさらに腹部末端の先端を前記物体や他の雄の下部に押しつけるという一連の行動を引き起こす活性（以下、「性刺激活性」と称する。）を示す。この一連の行動は、生きている雌に対する行動と全く同一で区別できない。   When the male sex beetle sex stimulant of the present invention comes into contact with a male sex beetle or tentacle, etc., the surface of the base material coated with the sex stimulant of the Japanese beetle beetle or other male beetle beetle males in the vicinity. On the other hand, it exhibits a stimulating activity and an activity that causes a series of actions (hereinafter referred to as “sexual stimulating activity”) that embraces it and presses the tip of the abdominal end against the lower part of the object or other male. This series of actions is exactly the same as the action on a living female and is indistinguishable.

（ゴマダラカミキリの防除剤）
本発明のゴマダラカミキリの防除剤は、本発明のゴマダラカミキリの性刺激剤を有効成分として含み、殺虫成分を含むことが好ましく、更に必要に応じてその他の成分を含む。 (Pesticide for longhorn beetle)
The control agent for the spotted longhorn beetle of the present invention contains the sex stimulant of the spotted longhorn beetle of the present invention as an active ingredient, preferably contains an insecticidal ingredient, and further contains other ingredients as necessary.

本発明のゴマダラカミキリの防除剤によれば、前記防除剤をゴマダラカミキリ発生域に設置又は散布することによって、雄成虫が前記性刺激剤を含む前記防除剤に長時間逗留し、雌成虫との交尾の機会が減少するため、次世代の生息密度を減じることができる。   According to the control agent of the spotted longhorn beetle of the present invention, by installing or spraying the control agent in the spot where the spotted longhorn beetle is generated, the male adult is allowed to stay in the control agent containing the sex stimulant for a long time, and mating with a female adult Because opportunities are reduced, the next generation density can be reduced.

＜殺虫成分＞
前記殺虫成分としては、特に制限はなく、目的に応じて適宜公知の殺虫成分を選択でき、例えば、合成殺虫活性成分、生物由来の殺虫活性成分などが挙げられる。
前記合成殺虫活性成分としては、例えば、有機リン、カーバメート、合成ピレスロイドなどが挙げられる。前記生物由来の殺虫活性成分としては、例えば、Ｂｅａｕｖｅｒｉａ ｂａｓｓｉａｎａ（白きょう病菌）等の昆虫病原糸状菌などが挙げられる。
これらの中でも、標的外生物に対する安全性が高い点で生物由来の殺虫活性成分が好ましい。 <Insecticide ingredient>
There is no restriction | limiting in particular as said insecticidal component, According to the objective, a well-known insecticidal component can be selected suitably, For example, a synthetic insecticidal active component, a biologically derived insecticidal active component, etc. are mentioned.
Examples of the synthetic insecticidal active ingredient include organic phosphorus, carbamate, and synthetic pyrethroid. Examples of the insecticidal active ingredient derived from the organism include entomopathogenic filamentous fungi such as Beauveria bassiana.
Among these, an insecticidal active ingredient derived from an organism is preferable in terms of high safety against non-target organisms.

本発明のゴマダラカミキリの防除剤によれば、前記白きょう病菌のように、前記合成殺虫活性成分に比べてやや速効性に劣る成分を用いる場合においても、ゴマダラカミキリ雄成虫が本発明のゴマダラカミキリの性刺激剤の作用によって、前記防除剤に長時間逗留し、前記殺虫成分に曝露される時間が長くなるため、前記殺虫成分の効力を十分に発揮させることができる。
前記殺虫成分を併用する場合には、本発明のゴマダラカミキリの防除剤は、不撚布及びスポンジ状物体の少なくともいずれかに含浸されてなる前記ゴマダラカミキリの性刺激剤及び前記殺虫成分を含むことが、ゴマダラカミキリの生息密度をより速効的かつ簡便に減じることができる点で好ましい。前記不撚布又はスポンジ状物体を、樹幹の周囲に巻くことによって、ゴマダラカミキリを防除することができる。 According to the control agent of the spotted longhorn beetle of the present invention, even when using a component that is slightly inferior to the synthetic insecticidal active component, such as the white scab, the male spotted longhorn beetle is sexually stimulating the spotted longhorn beetle of the present invention. Because of the action of the agent, the insecticide stays in the control agent for a long time and is exposed to the insecticidal component for a long time, so that the efficacy of the insecticidal component can be sufficiently exerted.
In the case of using the insecticidal component in combination, the control agent of the spotted beetle of the present invention comprises the sex stimulant of the spotted beetle impregnated in at least one of a non-twisted cloth and a sponge-like object, and the insecticidal component. This is preferable in that the population density of the long-horned beetle can be reduced more quickly and easily. By winding the untwisted cloth or sponge-like object around the trunk, it is possible to control the longhorn beetle.

以下、実施例に基づいて本発明をより具体的に説明するが、本発明は以下の実施例に制限されるものではない。   EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example, this invention is not restrict | limited to a following example.

（合成例１：化合物１の合成）
下記反応式（１）−１及び反応式（１）−２に示す通り、化合物１の合成を行った。 (Synthesis Example 1: Synthesis of Compound 1)
Compound 1 was synthesized as shown in the following reaction formula (1) -1 and reaction formula (1) -2.

＜化合物８の合成＞
Ｌ−酒石酸ジメチル（下記構造式７で表される化合物７、１．００１９ｇ、５．５７ｍｍｏｌ）とｐ−トルエンスルホン酸（ＰＴＳＡ、２１．４ｍｇ、０．１１ｍｍｏｌ）を２，２−ジメトキシプロパン（３．３ｍＬ、２６．１７ｍｍｏｌ）に溶解させた混合液を６０℃で１９時間撹拌した。０℃で飽和炭酸水素ナトリウム水溶液を加えクエンチした。さらに酢酸エチルを加え、飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄した。有機層を無水硫酸ナトリウムで乾燥させ、ろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物（下記構造式８で表される化合物８）を精製せず、次の反応に用いた。 <Synthesis of Compound 8>
Dimethyl L-tartrate (compound 7 represented by the following structural formula 7, 1.0019 g, 5.57 mmol) and p-toluenesulfonic acid (PTSA, 21.4 mg, 0.11 mmol) were mixed with 2,2-dimethoxypropane (3 .3 mL, 26.17 mmol) was stirred at 60 ° C. for 19 hours. The reaction was quenched by adding saturated aqueous sodium hydrogen carbonate solution at 0 ° C. Further, ethyl acetate was added, and the mixture was washed once with a saturated aqueous sodium hydrogen carbonate solution and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product (Compound 8 represented by the following structural formula 8) was used for the next reaction without purification.

＜化合物９の合成＞
得られた前記粗生成物をジエチルエーテル（１８．２ｍＬ）に溶解させ、０℃で水素化アルミニウムリチウム（４１３．７ｍｇ、１０．９０ｍｍｏｌ）を加え、室温で１時間１６分間撹拌した。ジエチルエーテルを加え、硫酸ナトリウム１０水和物（１７．５６ｇ、５４．５１ｍｍｏｌ）を加えクエンチし、終夜撹拌した。混合液をセライトろ過し、ろ液を減圧濃縮した。その粗生成物をシリカゲルカラムクロマトグラフィー（酢酸エチル）で精製し、淡黄色透明油状物として目的化合物（下記構造式９で表される化合物９、６５０．２ｍｇ、２段階収率７２．０％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 9>
The obtained crude product was dissolved in diethyl ether (18.2 mL), lithium aluminum hydride (413.7 mg, 10.90 mmol) was added at 0 ° C., and the mixture was stirred at room temperature for 1 hr 16 min. Diethyl ether was added and quenched with sodium sulfate decahydrate (17.56 g, 54.51 mmol) and stirred overnight. The mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate), and the target compound (compound 9, represented by structural formula 9 below, 650.2 mg, 2 step yield 72.0%) as a pale yellow transparent oily substance. Got. The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．０３（２Ｈ，ｄｄｄ，Ｊ＝３．８Ｈｚ，２．３Ｈｚ，１．４Ｈｚ），３．８２（２Ｈ，ｄｄｄ，Ｊ＝１１．８Ｈｚ，２．３Ｈｚ，１．４Ｈｚ），３．７０（２Ｈ，ｄｄｄ，Ｊ＝１１．８Ｈｚ，２．３Ｈｚ，１．４Ｈｚ），１．４４（６Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.03 (2H, ddd, J = 3.8 Hz, 2.3 Hz, 1.4 Hz), 3.82 (2H, ddd, J = 11.8 Hz, 2 .3 Hz, 1.4 Hz), 3.70 (2 H, ddd, J = 11.8 Hz, 2.3 Hz, 1.4 Hz), 1.44 (6 H, s)

＜化合物１０の合成＞
化合物９（６５０．２ｍｇ、４．０１ｍｍｏｌ）をテトラヒドロフラン（２０．１ｍＬ）に溶解させ、０℃で水素化ナトリウム（１９２．４ｍｇ、４．４１ｍｍｏｌ）を加え、０℃で３０分間撹拌した。０℃でｔｅｒｔ−ブチルジメチルシリルクロリド（６３８．７ｍｇ、４．４１ｍｍｏｌ）を加え、室温で１時間４０分間撹拌した。０℃で、飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：１、体積比）で精製し、淡黄色透明油状物として目的化合物（下記構造式１０で表される化合物１０、９８２．８ｍｇ、収率８８．５％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 10>
Compound 9 (650.2 mg, 4.01 mmol) was dissolved in tetrahydrofuran (20.1 mL), sodium hydride (192.4 mg, 4.41 mmol) was added at 0 ° C., and the mixture was stirred at 0 ° C. for 30 min. Tert-butyldimethylsilyl chloride (638.7 mg, 4.41 mmol) was added at 0 ° C., and the mixture was stirred at room temperature for 1 hour and 40 minutes. At 0 ° C., a saturated aqueous ammonium chloride solution was added to quench the reaction. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous solution of ammonium chloride and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1, volume ratio) to obtain the target compound (compound 10 represented by the following structural formula 10, 982.8 mg, as a pale yellow transparent oily product). Rate 88.5%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：３．９９（１Ｈ，ｄｄｄ，ｊ＝７．６Ｈｚ，４．６Ｈｚ，４．６Ｈｚ），３．９０−３．８５（２Ｈ，ｍ），３．８０−３．６４（３Ｈ，ｍ），１．４２（３Ｈ，ｓ），１．４０（３Ｈ，ｓ），０．９０（９Ｈ，ｓ），０．０９（６Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 3.99 (1H, ddd, j = 7.6 Hz, 4.6 Hz, 4.6 Hz), 3.90-3.85 (2H, m), 3. 80-3.64 (3H, m), 1.42 (3H, s), 1.40 (3H, s), 0.90 (9H, s), 0.09 (6H, s)

＜化合物１１の合成＞
化合物１０（５３４．１ｍｇ、１．９３ｍｍｏｌ）をジクロロメタン（９．７ｍＬ）に溶解させ、−４０℃でジイソプロピルエチルアミン（１ｍＬ、５．８０ｍｍｏｌ）を加え、さらに、−４０℃でトリフルオロメタンスルホン酸無水物（４８５μＬ、２．９０ｍｍｏｌ）を加え３７分間撹拌した。−４０℃で飽和炭酸水素ナトリウム水溶液を加えクエンチした。室温にし、さらに酢酸エチルを加え、飽和炭酸水素ナトリウム水溶液で１回、０．５規定塩酸で１回、さらに飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させた。ろ過により乾燥剤を除去した後、減圧濃縮し、粗生成物をショートシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：１、体積比）により原点成分を分離し、その粗生成物（下記構造式１１で表される化合物１１）を次の反応に用いた。 <Synthesis of Compound 11>
Compound 10 (534.1 mg, 1.93 mmol) was dissolved in dichloromethane (9.7 mL), diisopropylethylamine (1 mL, 5.80 mmol) was added at −40 ° C., and trifluoromethanesulfonic anhydride was further added at −40 ° C. (485 μL, 2.90 mmol) was added and stirred for 37 minutes. It quenched by adding saturated sodium hydrogencarbonate aqueous solution at -40 degreeC. Bring to room temperature, add ethyl acetate, wash once with saturated aqueous sodium bicarbonate, once with 0.5N hydrochloric acid, once with saturated aqueous sodium bicarbonate, and once with saturated brine, and dry the organic layer. Dry with sodium sulfate. After removing the desiccant by filtration, the filtrate was concentrated under reduced pressure, and the crude product was separated from the origin component by short silica gel column chromatography (hexane: ethyl acetate = 3: 1, volume ratio), and the crude product (the following structural formula) Compound 11) represented by 11 was used in the next reaction.

＜化合物１２の合成＞
シアン化銅（１８３．１ｍｇ、１．８４ｍｍｏｌ）をテトラヒドロフラン（１０ｍＬ）に溶解させ、０℃で２０分間撹拌した。０℃で臭化イソプロピルマグネシウム・テトラヒドロフラン溶液（４９．０ｍＬ、２４．５４ｍｍｏｌ）を加え３０分間撹拌した。さらに、０℃でベンゼンと共沸させ脱水した化合物１１（５．０１ｇ、１２．２７ｍｍｏｌ）をテトラヒドロフラン（３０ｍＬ）に溶解させた溶液を加え、３時間２０分間撹拌した。０℃で飽和塩化アンモニウム水溶液を加え、クエンチした。さらに酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝１５：１、体積比）で精製し、極淡黄色透明油状物として目的化合物（下記構造式１２で表される化合物１２、３．４３ｇ、収率９５．８％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 12>
Copper cyanide (183.1 mg, 1.84 mmol) was dissolved in tetrahydrofuran (10 mL) and stirred at 0 ° C. for 20 minutes. At 0 ° C., an isopropylmagnesium bromide-tetrahydrofuran solution (49.0 mL, 24.54 mmol) was added and stirred for 30 minutes. Further, a solution in which Compound 11 (5.01 g, 12.27 mmol) azeotropically distilled with benzene at 0 ° C. was dissolved in tetrahydrofuran (30 mL) was added, and the mixture was stirred for 3 hours and 20 minutes. Saturated aqueous ammonium chloride solution was added at 0 ° C. to quench. Further, ethyl acetate was added, and the mixture was washed once with a saturated aqueous ammonium chloride solution and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 15: 1, volume ratio), and the target compound (compound 12, represented by structural formula 12 below, 3.43 g, as an extremely pale yellow transparent oil) Yield 95.8%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）４．８３−４．８１（２Ｈ，ｍ），４．１３−４．１０（１Ｈ，ｍ），３．７６−３．６２（３Ｈ，ｍ），２．３５−２．３３（２Ｈ，ｍ），１．７９（３Ｈ，ｓ），１．４１（３Ｈ，ｓ），１．３９（３Ｈ，ｓ），０．９０（９Ｈ，ｓ），０．０７（６Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) 4.83-4.81 (2H, m), 4.13-4.10 (1H, m), 3.76-3.62 (3H, m), 2 .35-2.33 (2H, m), 1.79 (3H, s), 1.41 (3H, s), 1.39 (3H, s), 0.90 (9H, s),. 07 (6H, s)

＜化合物１３の合成＞
化合物１２（３．９１ｇ、１３．００ｍｍｏｌ）をテトラヒドロフラン（４５．５ｍＬ）に溶解させ、室温でフッ化テトラブチルアンモニウム・テトラヒドロフラン溶液（１９．５ｍＬ、１９．５０ｍｍｏｌ）を加え、室温で１時間撹拌した。０℃で、飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄した。水層に溶解した生成物を酢酸エチルで４回逆抽出した。有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：１、体積比）で精製し、淡黄色透明油状物として目的化合物（下記構造式１３で表される化合物１３、２．３８ｇ、収率９８．０％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 13>
Compound 12 (3.91 g, 13.00 mmol) was dissolved in tetrahydrofuran (45.5 mL), tetrabutylammonium fluoride / tetrahydrofuran solution (19.5 mL, 19.50 mmol) was added at room temperature, and the mixture was stirred at room temperature for 1 hour. . At 0 ° C., a saturated aqueous ammonium chloride solution was added to quench the reaction. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous ammonium chloride solution and once with a saturated saline solution. The product dissolved in the aqueous layer was back extracted four times with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the desiccant was removed by filtration, followed by concentration under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1, volume ratio) to obtain the target compound (compound 13, represented by the following structural formula 13, 2.38 g, as a pale yellow transparent oily substance). The rate was 98.0%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．８５−４．８２（２Ｈ，ｍ），４．０９（１Ｈ，ｄｄｄ，Ｊ＝７．８Ｈｚ，７．４Ｈｚ，５．５Ｈｚ），３．８３−３．７４（２Ｈ，ｍ），３．５８（１Ｈ，ｄｄ，Ｊ＝１１．８Ｈｚ，４．１Ｈｚ），２．３９（２Ｈ，ｄｄ，Ｊ＝１４．２Ｈｚ，７．３Ｈｚ）２．２６（２Ｈ，ｄｄ，Ｊ＝１４．２Ｈｚ，５．５Ｈｚ），１．７８（３Ｈ，ｓ），１．４３（３Ｈ，ｓ），１．４２（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.85-4.82 (2H, m), 4.09 (1H, ddd, J = 7.8 Hz, 7.4 Hz, 5.5 Hz), 3. 83-3.74 (2H, m), 3.58 (1H, dd, J = 11.8 Hz, 4.1 Hz), 2.39 (2H, dd, J = 14.2 Hz, 7.3 Hz) 26 (2H, dd, J = 14.2 Hz, 5.5 Hz), 1.78 (3H, s), 1.43 (3H, s), 1.42 (3H, s)

＜化合物１４の合成＞
塩化オキサリル・ジクロロメタン溶液（２０ｍＬ、３８．３４ｍｍｏｌ）を室温でジクロロメタン（１０ｍＬ）に加え、−７０℃に冷却した。そこに、ジクロロメタン（１０ｍＬ）に溶解させたジメチルスルホキシド（５．５ｍＬ、７６．６８ｍｍｏｌ）を−７０℃で加え、３０分間撹拌した。ベンゼンと共沸させ脱水した化合物１３（２．３８ｇ、１２．７８ｍｍｏｌ）をジクロロメタン（２０ｍＬ）に溶解させ、−７０℃で加え、３０分間撹拌した。さらに、−７０℃でトリエチルアミン（１３．４ｍＬ、９５．８５ｍｍｏｌ）を加え３０分間撹拌した。フラスコ内の固形物が溶解しなかったため、ジクロロメタン（２０ｍＬ）を追加した。−４０℃までゆるやかに昇温させ、十分な水に溶解させたリン酸二水素ナトリウム（１２．０ｍｇ、７６．６８ｍｍｏｌ）を加え、さらにゆるやかに室温まで昇温させた。室温でｔｅｒｔ−ブタノール（６４．０ｍＬ）を加え、さらに、室温で、２−ｍｅｔｈｙｌ−２−ｂｕｔｅｎｅを加えた。さらに０℃で亜塩素酸ナトリウム（８．８ｇ、７６．６８ｍｍｏｌ）を加え、室温で１時間撹拌した。室温でリン酸二水素ナトリウム（４．０ｍｇ、２５．５６ｍｍｏｌ）を加え、さらに、０℃で亜塩素酸ナトリウム（２．９０ｇ、２５．５６ｍｍｏｌ）を加え、室温で１時間撹拌した。０℃で飽和食塩水を加え、クエンチした。酢酸エチルを加え、飽和食塩水で１回洗浄し、水層を３回酢酸エチルで逆抽出した。有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物（下記構造式１４で表される化合物１４）をそのまま次の反応へ用いた。 <Synthesis of Compound 14>
Oxalyl chloride / dichloromethane solution (20 mL, 38.34 mmol) was added to dichloromethane (10 mL) at room temperature and cooled to -70 ° C. Dimethyl sulfoxide (5.5 mL, 76.68 mmol) dissolved in dichloromethane (10 mL) was added thereto at −70 ° C., and the mixture was stirred for 30 minutes. Compound 13 (2.38 g, 12.78 mmol) azeotroped with benzene and dehydrated was dissolved in dichloromethane (20 mL), added at −70 ° C., and stirred for 30 minutes. Further, triethylamine (13.4 mL, 95.85 mmol) was added at −70 ° C., and the mixture was stirred for 30 minutes. Dichloromethane (20 mL) was added because the solid in the flask did not dissolve. The temperature was raised gently to −40 ° C., sodium dihydrogen phosphate (12.0 mg, 76.68 mmol) dissolved in sufficient water was added, and the temperature was further raised to room temperature. Tert-butanol (64.0 mL) was added at room temperature, and 2-methyl-2-butene was further added at room temperature. Further, sodium chlorite (8.8 g, 76.68 mmol) was added at 0 ° C., and the mixture was stirred at room temperature for 1 hour. Sodium dihydrogen phosphate (4.0 mg, 25.56 mmol) was added at room temperature, sodium chlorite (2.90 g, 25.56 mmol) was further added at 0 ° C., and the mixture was stirred at room temperature for 1 hour. Saturated brine was added at 0 ° C. to quench. Ethyl acetate was added, washed once with saturated brine, and the aqueous layer was back extracted three times with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the desiccant was removed by filtration, followed by concentration under reduced pressure. The crude product (compound 14 represented by the following structural formula 14) was directly used in the next reaction.

＜化合物１５の合成＞
化合物１４を含む粗生成物をジクロロメタンに溶解させ、０℃でジイソプロピルエチルアミン（３．７ｍＬ、２１．７３ｍｍｏｌ）、Ｎ，Ｏ−ジメチルヒドロキシルアミン塩酸塩（２．１２ｇ、２１．７３ｍｍｏｌ）、ジシクロヘキシルカルボジイミド（４．００ｇ、１９．１７ｍｍｏｌ）、及びＮ，Ｎ−ジメチル−４−アミノピリジン（１．５８ｇ、１２．７８ｍｍｏｌ）を加え、１５時間撹拌した。０℃で飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、セライトろ過により固形物を除去した。ろ液を飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させた。ろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：１、体積比）で精製し、淡黄色透明油状物として目的化合物（下記構造式１５で表される化合物１５、２．２５ｇ、３段階収率７２．３％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 15>
The crude product containing compound 14 was dissolved in dichloromethane and diisopropylethylamine (3.7 mL, 21.73 mmol), N, O-dimethylhydroxylamine hydrochloride (2.12 g, 21.73 mmol), dicyclohexylcarbodiimide ( 4.00 g, 19.17 mmol) and N, N-dimethyl-4-aminopyridine (1.58 g, 12.78 mmol) were added and stirred for 15 hours. Quenched by adding saturated aqueous ammonium chloride at 0 ° C. Ethyl acetate was added and the solid was removed by celite filtration. The filtrate was washed once with saturated aqueous ammonium chloride solution and once with saturated brine, and the organic layer was dried over anhydrous sodium sulfate. The desiccant was removed by filtration and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1, volume ratio) to give the target compound (compound 15, represented by the following structural formula 15, 2.25 g, 3) as a pale yellow transparent oily substance. A step yield of 72.3%) was obtained. The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．８２−４．８０（２Ｈ，ｍ），４．６２（１Ｈ，ｍ），４．４８（１Ｈ，ｍ），３．７３（３Ｈ，ｓ），３．２２（３Ｈ，ｓ），２．４２（１Ｈ，ｄｄ，ｊ＝１４．６Ｈｚ，７．７Ｈｚ），２．３７（１Ｈ，ｄｄ，ｊ＝１４．６Ｈｚ，７．７Ｈｚ），１．７８（３Ｈ，ｓ），１．４８（３Ｈ，ｓ），１．４７（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.82-4.80 (2H, m), 4.62 (1H, m), 4.48 (1H, m), 3.73 (3H, s ), 3.22 (3H, s), 2.42 (1H, dd, j = 14.6 Hz, 7.7 Hz), 2.37 (1H, dd, j = 14.6 Hz, 7.7 Hz), 1 .78 (3H, s), 1.48 (3H, s), 1.47 (3H, s)

＜化合物１６の合成＞
ベンゼンと共沸させ脱水した化合物１５（１．２２ｇ、５．０１ｍｍｏｌ）をトルエンに溶解させ、−１０℃で臭化メチルマグネシウム・ジエチルエーテル溶液（２．５ｍＬ、７．５２ｍｍｏｌ）を加え、−１０℃で１時間撹拌した。−１０℃で飽和塩化アンモニウム水溶液でクエンチし、室温でｎ−ペンタンを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄した。有機層をシリカゲルろ過した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ｎ−ペンタン：ジエチルエーテル＝８：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式１６で表される化合物１６、９０１．８ｍｇ、収率９０．７％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 16>
Compound 15 (1.22 g, 5.01 mmol) dehydrated by azeotroping with benzene was dissolved in toluene, and a methylmagnesium bromide-diethyl ether solution (2.5 mL, 7.52 mmol) was added at −10 ° C., and −10 Stir for 1 hour at ° C. Quenched with a saturated aqueous ammonium chloride solution at −10 ° C., added n-pentane at room temperature, and washed once with a saturated aqueous ammonium chloride solution and once with a saturated saline solution. The organic layer was filtered through silica gel and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (n-pentane: diethyl ether = 8: 1, volume ratio), and the target compound (compound 16, represented by the following structural formula 16, 901.8 mg, as a colorless transparent oil) Yield 90.7%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．８６−４．８２（２Ｈ，ｍ），４．１６（１Ｈ，ｔｄ，Ｊ＝７．７Ｈｚ，３．７Ｈｚ），２．４５（１Ｈ，ｄｄ，Ｊ＝１４．７Ｈｚ，３．７Ｈｚ），２．３４（１Ｈ，ｄｄ，Ｊ＝１４．７Ｈｚ，７．７Ｈｚ），２．２８（３Ｈ，ｓ）１．７８（３Ｈ，ｓ），１．４６（３Ｈ，ｓ），１．４２（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.86-4.82 (2H, m), 4.16 (1H, td, J = 7.7 Hz, 3.7 Hz), 2.45 (1H, dd, J = 14.7 Hz, 3.7 Hz), 2.34 (1H, dd, J = 14.7 Hz, 7.7 Hz), 2.28 (3H, s) 1.78 (3H, s), 1 .46 (3H, s), 1.42 (3H, s)

＜化合物１７の合成＞
切削片状マグネシウム（４７．５ｍｇ、１．９５ｍｍｏｌ）を真空中でヒートガンにより５分間加熱した。ジエチルエーテル（２．０ｍＬ）を加え、さらに、１，２−ジブロモエタン（２滴）を加えた。５分間超音波に当て、ジエチルエーテル（３．０ｍＬ）に溶解させたＭＰＭＯ（ＣＨ２）３Ｂｒ（２５３．３ｍｇ、０．９８ｍｍｏｌ）を加え３０分間撹拌した。ジエチルエーテル（４．０ｍｌ）に溶解させた化合物１６（６４．６ｍｇ、０．３３ｍｍｏｌ）を加え、室温で１時間撹拌した。０℃で飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：１、体積比）で精製し、淡黄色透明油状物として目的化合物（下記構造式１７で表される化合物１７、１１７．２ｍｇ、収率９５．１％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 17>
Chip-like magnesium (47.5 mg, 1.95 mmol) was heated in a vacuum with a heat gun for 5 minutes. Diethyl ether (2.0 mL) was added, followed by 1,2-dibromoethane (2 drops). Sonicated for 5 minutes, MPMO (CH 2 ) 3 Br (253.3 mg, 0.98 mmol) dissolved in diethyl ether (3.0 mL) was added and stirred for 30 minutes. Compound 16 (64.6 mg, 0.33 mmol) dissolved in diethyl ether (4.0 ml) was added, and the mixture was stirred at room temperature for 1 hour. Quenched by adding saturated aqueous ammonium chloride at 0 ° C. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous solution of ammonium chloride and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1, volume ratio) to obtain the target compound (compound 17, 117.2 mg represented by the following structural formula 17 as a pale yellow transparent oil). Rate 95.1%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：７．２７−７．２３（２Ｈ，ｍ），６．８９−６．８６（２Ｈ，ｍ），４．８４−４．８０（２Ｈ，ｍ），４．４４（２Ｈ，ｓ），４．１９（１Ｈ，ｄｄｄ，Ｊ＝９．１Ｈｚ，７．７Ｈｚ，２．９Ｈｚ），３．８０（３Ｈ，ｓ），３．５９（１Ｈ，ｄ，Ｊ＝７．７Ｈｚ），３．４６（２Ｈ，ｔ，Ｊ＝６．３Ｈｚ），２．３３（２Ｈ，ｍ），２．２６（１Ｈｄｄ，Ｊ＝１４．７Ｈｚ，９．１Ｈｚ），１．８０（３Ｈ，ｓ），１．７５−１．５８（４Ｈ，ｍ），１．４１（３Ｈ，ｓ），１．４０（３ｈ，ｓ），１．１１（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 7.27-7.23 (2H, m), 6.89-6.86 (2H, m), 4.84-4.80 (2H, m) , 4.44 (2H, s), 4.19 (1H, ddd, J = 9.1 Hz, 7.7 Hz, 2.9 Hz), 3.80 (3H, s), 3.59 (1H, d, J = 7.7 Hz), 3.46 (2 H, t, J = 6.3 Hz), 2.33 (2 H, m), 2.26 (1 Hdd, J = 14.7 Hz, 9.1 Hz), 1. 80 (3H, s), 1.75-1.58 (4H, m), 1.41 (3H, s), 1.40 (3h, s), 1.11 (3H, s)

＜化合物１８の合成＞
化合物１７（７７８．９ｍｇ、２．０６ｍｍｏｌ）をＮ，Ｎ−ジメチルホルムアミド（１５ｍＬ）に溶解させ、０℃で水素化ナトリウム（４４９．０ｍｇ、１０．２９ｍｍｏｌ）を加え、３０分間撹拌した。０℃のまま、臭化アリル（１．３５ｍＬ、１５．４３ｍｍｏｌ）、ヨウ化テトラブチルアンモニウム（７７５．６ｍｇ、２．０６ｍｍｏｌ）を加え、室温で２時間３０分間撹拌した。０℃で飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、水層を酢酸エチルで２回逆抽出した。有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝９：１、体積比）で精製し、淡黄色透明油状物として目的化合物（下記構造式１８で表される化合物１８、８２４．４ｍｇ、収率９５．７％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 18>
Compound 17 (778.9 mg, 2.06 mmol) was dissolved in N, N-dimethylformamide (15 mL), sodium hydride (449.0 mg, 10.29 mmol) was added at 0 ° C., and the mixture was stirred for 30 min. While maintaining at 0 ° C., allyl bromide (1.35 mL, 15.43 mmol) and tetrabutylammonium iodide (775.6 mg, 2.06 mmol) were added, and the mixture was stirred at room temperature for 2 hours and 30 minutes. Quenched by adding saturated aqueous ammonium chloride at 0 ° C. Ethyl acetate was added, washed once with a saturated aqueous ammonium chloride solution and once with a saturated saline solution, and the aqueous layer was back extracted twice with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the desiccant was removed by filtration, followed by concentration under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 9: 1, volume ratio) to obtain the target compound (compound 18, 824.4 mg represented by the following structural formula 18 as a pale yellow transparent oil). Rate 95.7%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：７．２９−７．２４（２Ｈ，ｍ），６．９２−６．８７（２Ｈ，ｍ），５．８９（１Ｈ，ｄｄｔ，Ｊ＝１７．２Ｈｚ，１０．４Ｈｚ，５．２Ｈｚ），５．２４（１Ｈ，ｄｄｄ，Ｊ＝１７．２Ｈｚ，３．５Ｈｚ，１．７Ｈｚ），５．０８（１Ｈ，ｄｄｄ，Ｊ＝１０．４Ｈｚ，３．５Ｈｚ，１．７Ｈｚ），４．８５−４．７８（２Ｈ，ｍ），４．４３（２Ｈ，ｓ），４．１７（１Ｈ，ｄｄｄ，Ｊ＝９．９Ｈｚ，７．５Ｈｚ，２．６Ｈｚ），４．０８（１Ｈ，ｄｄｔ，Ｊ＝１２．５Ｈｚ，５．２Ｈｚ，１．５Ｈｚ），３．９８（１Ｈ，ｄｄｔ，Ｊ＝１２．５Ｈｚ，５．２Ｈｚ，１．５Ｈｚ），３．８０（３Ｈ，ｓ），３．７６（１Ｈ，ｄ，Ｊ＝７．４Ｈｚ），３．４７−３．４０（２Ｈ，ｍ），２．３７（１Ｈ，ｄ，Ｊ＝１４．９Ｈｚ），２．２４（１Ｈ，ｄｄ，Ｊ＝１４．９Ｈｚ，９．７Ｈｚ），１．７９（３Ｈ，ｓ），１．７５−１．５８（４Ｈ，ｍ），１．４２（３Ｈ，ｓ），１．３８（３Ｈ，ｓ），１．２０（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 7.29-7.24 (2H, m), 6.92-6.87 (2H, m), 5.89 (1H, ddt, J = 17. 2 Hz, 10.4 Hz, 5.2 Hz), 5.24 (1 H, ddd, J = 17.2 Hz, 3.5 Hz, 1.7 Hz), 5.08 (1 H, ddd, J = 10.4 Hz, 3. 5 Hz, 1.7 Hz), 4.85-4.78 (2 H, m), 4.43 (2 H, s), 4.17 (1 H, ddd, J = 9.9 Hz, 7.5 Hz, 2.6 Hz) ), 4.08 (1H, ddt, J = 12.5 Hz, 5.2 Hz, 1.5 Hz), 3.98 (1H, ddt, J = 12.5 Hz, 5.2 Hz, 1.5 Hz), 3. 80 (3H, s), 3.76 (1H, d, J = 7.4 Hz), 3.47-3.40 (2H, m), 2 37 (1H, d, J = 14.9 Hz), 2.24 (1 H, dd, J = 14.9 Hz, 9.7 Hz), 1.79 (3H, s), 1.75-1.58 (4H , M), 1.42 (3H, s), 1.38 (3H, s), 1.20 (3H, s)

＜化合物１９の合成＞
化合物１８（４０９．２ｍｇ、０．９８ｍｍｏｌ）をジクロロメタン（２３０ｍＬ）に溶解させた。ジクロロメタン（１５ｍＬ）に溶解させた第二世代グラブズ触媒（４１．５ｍｇ、０．０５ｍｍｏｌ）を加えて５０℃に昇温させ２時間撹拌した。さらに室温で第二世代グラブズ触媒（２０ｍｇ、０．０２ｍｍｏｌ）を追加し、５０℃で１時間撹拌した。別に化合物１８（３９６．２ｍｇ、０．９５ｍｍｏｌ）をジクロロメタン（２００ｍＬ）に溶解させた。ジクロロメタン（３７ｍＬ）に溶解させた第二世代グラブズ触媒（８０．４ｍｇ、０．１０ｍｍｏｌ）を加えて５０℃に昇温させ１時間３０分間撹拌した。そのまま減圧濃縮を行い、粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：１、体積比）で精製し、黄褐色透明油状物として目的化合物（下記構造式１９で表される化合物１９、６９９．９ｍｇ、収率９３．１％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 19>
Compound 18 (409.2 mg, 0.98 mmol) was dissolved in dichloromethane (230 mL). Second generation Grubbs catalyst (41.5 mg, 0.05 mmol) dissolved in dichloromethane (15 mL) was added, the temperature was raised to 50 ° C., and the mixture was stirred for 2 hours. Furthermore, the 2nd generation Grubbs catalyst (20 mg, 0.02 mmol) was added at room temperature, and it stirred at 50 degreeC for 1 hour. Separately, compound 18 (396.2 mg, 0.95 mmol) was dissolved in dichloromethane (200 mL). Second generation Grubbs catalyst (80.4 mg, 0.10 mmol) dissolved in dichloromethane (37 mL) was added, the temperature was raised to 50 ° C., and the mixture was stirred for 1 hour 30 minutes. Concentrated under reduced pressure, the crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1, volume ratio) to give the target compound (compound 19 represented by the following structural formula 19 as a tan transparent oil). 699.9 mg, 93.1% yield). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：７．２９−７．２４（２Ｈ，ｍ），６．９０−６．８５（２Ｈ，ｍ），５．５５−５．４８（１Ｈ，ｍ），４．４４（２Ｈ，ｓ），４．３３（１Ｈ，ｄｄｄ，Ｊ＝８．３Ｈｚ，７．５Ｈｚ，４．３Ｈｚ），３．９３−３．９１（３Ｈ，ｍ），３．５０−３．４０（２Ｈ，ｍ），２．７６（１Ｈ，ｄｄ，Ｊ＝１６．３Ｈｚ，４．３Ｈｚ），２．３３（１Ｈ，ｄｄ，Ｊ＝１６．３Ｈｚ，７．５Ｈｚ），１．７７（３Ｈ，ｓ），１．７４−１．６３（４Ｈ，ｍ），１．３６（３Ｈ，ｓ），１．２７（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 7.29-7.24 (2H, m), 6.90-6.85 (2H, m), 5.55-5.48 (1H, m) 4.44 (2H, s), 4.33 (1H, ddd, J = 8.3 Hz, 7.5 Hz, 4.3 Hz), 3.93-3.91 (3H, m), 3.50−. 3.40 (2H, m), 2.76 (1H, dd, J = 16.3 Hz, 4.3 Hz), 2.33 (1H, dd, J = 16.3 Hz, 7.5 Hz), 1.77 (3H, s), 1.74-1.63 (4H, m), 1.36 (3H, s), 1.27 (3H, s)

＜化合物２０の合成＞
化合物１９（４９．９ｍｇ、０．１３ｍｍｏｌ）をメタノールに溶解させ、０℃で、１規定塩酸（０．５ｍＬ、０．５０ｍｍｏｌ）を加え、０℃で１時間、室温で１時間撹拌し、飽和炭酸水素ナトリウム水溶液を加えクエンチした。酢酸エチルを加え、飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝２：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式２０で表される化合物２０、４３．２ｍｇ、収率９６．４％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 20>
Compound 19 (49.9 mg, 0.13 mmol) was dissolved in methanol, 1N hydrochloric acid (0.5 mL, 0.50 mmol) was added at 0 ° C., and the mixture was stirred at 0 ° C. for 1 hour and at room temperature for 1 hour, saturated. Aqueous sodium bicarbonate was added to quench. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous sodium hydrogen carbonate solution and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1, volume ratio), and the target compound (compound 20, represented by Structural Formula 20 below, 43.2 mg, yield) was obtained as a colorless transparent oil. 96.4%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：７．３０−７．２０（２Ｈ，ｍ），６．９０−６．８５（２Ｈ，ｍ），４．４３（２Ｈ，ｓ），４．２０−４．１６（２Ｈ，ｍ），３．９２−３．８５（２Ｈ，ｍ），３．８１（３Ｈ，ｓ），３．７１（１Ｈ，ｄｄ，Ｊ＝８．９Ｈｚ，４．１Ｈｚ），３．５３−３．３８（３Ｈ，ｍ），２．１５−２．１０（１Ｈ，ｍ），２．０３−１．９２（２Ｈ，ｍ），１．８１（３Ｈ，ｄｄ，Ｊ＝３．６Ｈｚ，２．０Ｈｚ），１．７９−１．６４（４Ｈ，ｍ），１．２７（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 7.30-7.20 (2H, m), 6.90-6.85 (2H, m), 4.43 (2H, s), 4.20 -4.16 (2H, m), 3.92-3.85 (2H, m), 3.81 (3H, s), 3.71 (1H, dd, J = 8.9 Hz, 4.1 Hz) , 3.53-3.38 (3H, m), 2.15-2.10 (1H, m), 2.03-1.92 (2H, m), 1.81 (3H, dd, J = 3.6 Hz, 2.0 Hz), 1.79-1.64 (4H, m), 1.27 (3H, s)

＜化合物２１ａ及び化合物２１ｂの合成＞
化合物２０（５８９．９ｍｇ、１．６８ｍｍｏｌ）をジメチルスルホキシド（８．４ｍＬ）に溶解させ、室温で２−ヨードキシ安息香酸（１．４０ｇ、５．０５ｍｍｏｌ）を加え、室温で２時間撹拌した。飽和炭酸水素ナトリウム水溶液を加えクエンチした。さらに酢酸エチルを加え、２時間撹拌した。その後飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄し、水層を酢酸エチルで１回逆抽出した。有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝２：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式２１ｂで表される化合物２１ｂ及び下記構造式２１ａで表される化合物２１ａの混合物、５５９．７ｍｇ、収率９６．０％）を得た。さらに高速液体クロマトグラフィー（ヘキサン：酢酸エチル＝２：１、体積比）でジアステレオマーの分離を行った。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 21a and Compound 21b>
Compound 20 (589.9 mg, 1.68 mmol) was dissolved in dimethyl sulfoxide (8.4 mL), 2-iodoxybenzoic acid (1.40 g, 5.05 mmol) was added at room temperature, and the mixture was stirred at room temperature for 2 hours. Saturated aqueous sodium hydrogen carbonate solution was added to quench. Further ethyl acetate was added and stirred for 2 hours. Thereafter, the mixture was washed once with a saturated aqueous sodium hydrogen carbonate solution and once with a saturated saline solution, and the aqueous layer was back extracted once with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the desiccant was removed by filtration, followed by concentration under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1, volume ratio) to give the target compound (compound 21b represented by the following structural formula 21b and the following structural formula 21a as a colorless transparent oil). Of the compound 21a, 559.7 mg, yield 96.0%). Further, diastereomers were separated by high performance liquid chromatography (hexane: ethyl acetate = 2: 1, volume ratio). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

−化合物２１ｂ−
１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：７．２８−７．２５（２Ｈ，ｍ），６．９０−６．８７（２Ｈ，ｍ），６．０２−５．９８（１Ｈ，ｍ），４．４５（２Ｈ，ｓ），３．９８（１Ｈ，ｄｄ，Ｊ＝９．７Ｈｚ，６．８Ｈｚ），３．８１（３Ｈ，ｓ），３．７６（１Ｈ，ｄｄ，９．７Ｈｚ，２．３Ｈｚ），３．５０−３．４５（２Ｈ，ｍ），３．１６−３．１０（１Ｈ，ｍ），２．７４−２．６９（１Ｈ，ｂｓ），２．１４（３Ｈ，ｔ，Ｊ＝２．３Ｈｚ），１．６８（２Ｈ，ｍ），１．６０−１．５０（２Ｈ，ｍ），１．１０（３Ｈ，ｓ）
−化合物２１ａ−
１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：７．２５−７．２２（２Ｈ，ｍ），６．８７−６．８４（２Ｈ，ｍ），６．０２−５．９８（１Ｈ，ｍ），４．４０（２Ｈ，ｓ），４．０３（１Ｈ，ｄｄ，Ｊ＝９．７Ｈｚ，６．６Ｈｚ），３．８０（３Ｈ，ｓ），３．７７（１Ｈ，ｄｄ，９．７Ｈｚ，２．２Ｈｚ），３．３８（２Ｈ，ｔ，Ｊ＝６．６Ｈｚ），３．１５５−３．１０（１Ｈ，ｍ），２．６６−２．６１（１Ｈ，ｍ），２．１４（３Ｈ，ｔ，Ｊ＝２．２Ｈｚ），１．８０−１．５０（３Ｈ，ｍ），１．４０−１．３３（１Ｈ，ｍ），１．２６（３Ｈ，ｓ） -Compound 21b-
1 H-NMR (400 MHz, CDCl 3 ) δ: 7.28-7.25 (2H, m), 6.90-6.87 (2H, m), 6.02-5.98 (1H, m) , 4.45 (2H, s), 3.98 (1H, dd, J = 9.7 Hz, 6.8 Hz), 3.81 (3H, s), 3.76 (1H, dd, 9.7 Hz, 2.3 Hz), 3.50-3.45 (2H, m), 3.16-3.10 (1H, m), 2.74-2.69 (1H, bs), 2.14 (3H, t, J = 2.3 Hz), 1.68 (2H, m), 1.60-1.50 (2H, m), 1.10 (3H, s)
-Compound 21a-
1 H-NMR (400 MHz, CDCl 3 ) δ: 7.25-7.22 (2H, m), 6.87-6.84 (2H, m), 6.02-5.98 (1H, m) , 4.40 (2H, s), 4.03 (1H, dd, J = 9.7 Hz, 6.6 Hz), 3.80 (3H, s), 3.77 (1H, dd, 9.7 Hz, 2.2 Hz), 3.38 (2 H, t, J = 6.6 Hz), 3.155-3.10 (1 H, m), 2.66-2.61 (1 H, m), 2.14 ( 3H, t, J = 2.2 Hz), 1.80-1.50 (3H, m), 1.40-1.33 (1H, m), 1.26 (3H, s)

＜化合物２２の合成＞
化合物２１ｂ（５８．５ｍｇ、０．１７ｍｍｏｌ）をメタノール（１．７ｍＬ）に溶解させ、室温で水酸化パラジウム／炭素（１５．０ｍｇ、５．０質量％）を加え、水素置換により、水素雰囲気下で１時間撹拌した。窒素置換をして、セライトろ過により水酸化パラジウム／炭素を除去して減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（酢酸エチルのみ）で精製し、白色結晶として目的化合物（下記構造式２２で表される化合物２２、３７．４ｍｇ、収率９７．１％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 22>
Compound 21b (58.5 mg, 0.17 mmol) was dissolved in methanol (1.7 mL), palladium hydroxide / carbon (15.0 mg, 5.0 mass%) was added at room temperature, and hydrogen substitution was performed under a hydrogen atmosphere. For 1 hour. After replacing with nitrogen, palladium hydroxide / carbon was removed by Celite filtration, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate only) to obtain the target compound (compound 22, represented by the following structural formula 22, 37.4 mg, yield 97.1%) as white crystals. The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．０２（１Ｈ，ｄｄ，Ｊ＝１０．３Ｈｚ，３．９Ｈｚ），３．９７（１Ｈ，ｄｄ，Ｊ＝１０．３Ｈｚ，７．３Ｈｚ），３．７４−３．６２（２Ｈ，ｍ），２．７３−２．６６（１Ｈ，ｍ），２．４０−２．３３（２Ｈ，ｍ），１．８８−１．７６（１Ｈ，ｍ），１．７３−１．５２（３Ｈ，ｍ），１．１７（３Ｈ，ｄ，Ｊ＝６．２Ｈｚ），１．０４（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.02 (1H, dd, J = 10.3 Hz, 3.9 Hz), 3.97 (1H, dd, J = 10.3 Hz, 7.3 Hz), 3.74-3.62 (2H, m), 2.73-2.66 (1H, m), 2.40-2.33 (2H, m), 1.88-1.76 (1H, m ), 1.73-1.52 (3H, m), 1.17 (3H, d, J = 6.2 Hz), 1.04 (3H, s)

＜化合物２３の合成＞
化合物２２（４８．０ｍｇ、０．２１ｍｍｏｌ）をジクロロメタンに溶解させ、室温でピリジン（５０．８μＬ、０．６３ｍｍｏｌ）、塩化トリクロロアセチル（３６．１μＬ、０．３２ｍｍｏｌ）を加え、３０分間撹拌した。０℃で飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝２：１、体積比）で精製し、淡黄色透明油状物として目的化合物（下記構造式２３で表される化合物２３、６６．８ｍｇ、収率８５．０％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 23>
Compound 22 (48.0 mg, 0.21 mmol) was dissolved in dichloromethane, pyridine (50.8 μL, 0.63 mmol) and trichloroacetyl chloride (36.1 μL, 0.32 mmol) were added at room temperature, and the mixture was stirred for 30 minutes. Quenched by adding saturated aqueous ammonium chloride at 0 ° C. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous solution of ammonium chloride and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1, volume ratio) to obtain the target compound (compound 23, 66.8 mg represented by the following structural formula 23, 66.8 mg) as a pale yellow transparent oily substance. 85.0%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．３９（２Ｈ，ｔ，Ｊ＝６．３Ｈｚ），３．９９（１Ｈ，ｄｄ，Ｊ＝１０．３Ｈｚ，３．２Ｈｚ），３．９３（１Ｈ，ｄｄ，Ｊ＝１０．３Ｈｚ，７．９Ｈｚ），２．８０−２．７２（１Ｈ，ｍ），２．７０−２．６３（１Ｈ，ｍ），２／４０−２／３２（３Ｈ，ｍ），１．９２−１．７２（３Ｈ，ｍ），１．６２−１．５２（１Ｈ，ｍ），１．１７（３Ｈ，ｄ，Ｊ＝６．１Ｈｚ），１．０３（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.39 (2H, t, J = 6.3 Hz), 3.99 (1H, dd, J = 10.3 Hz, 3.2 Hz), 3.93 ( 1H, dd, J = 10.3 Hz, 7.9 Hz), 2.80-2.72 (1H, m), 2.70-2.63 (1H, m), 2 / 40-2 / 32 (3H , M), 1.92-1.72 (3H, m), 1.62-1.52 (1H, m), 1.17 (3H, d, J = 6.1 Hz), 1.03 (3H , S)

＜化合物２４の合成＞
化合物２３（６６．８ｍｇ、０．１８ｍｍｏｌ）をジクロロメタンに溶解させ、０℃で、２，６−ルチジン（１８７．４μＬ、１．６１ｍｍｏｌ）とトリフルオロメタンスルホン酸トリメチルシリル（１５５．５μＬ、０．８１ｍｍｏｌ）を加え、室温で３０分間撹拌した。０℃で飽和炭酸水素ナトリウム水溶液を加えクエンチした。酢酸エチルを加え、飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝５：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式２４で表される化合物２４、７５．５ｍｇ、収率９４．７％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 24>
Compound 23 (66.8 mg, 0.18 mmol) was dissolved in dichloromethane and at 0 ° C., 2,6-lutidine (187.4 μL, 1.61 mmol) and trimethylsilyl trifluoromethanesulfonate (155.5 μL, 0.81 mmol) And stirred at room temperature for 30 minutes. The reaction was quenched by adding saturated aqueous sodium hydrogen carbonate solution at 0 ° C. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous sodium hydrogen carbonate solution and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 5: 1, volume ratio), and the target compound (compound 24 represented by the following structural formula 24, 75.5 mg, yield) was obtained as a colorless transparent oil. 94.7%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．４４−４．３８（２Ｈ，ｍ），３．９７（１Ｈ，ｄｄ，Ｊ＝１０．２Ｈｚ，３．７Ｈｚ），３．９２（１Ｈ，ｄｄ，Ｊ＝１０．７Ｈｚ，７．９Ｈｚ），２．６５−２．５８（１Ｈ，ｍ），２．４７−２．３４（１Ｈ，ｍ），２，３３（１Ｈ，ｄｄｄ，Ｊ＝１６．２Ｈｚ，６．３Ｈｚ，１．９Ｈｚ），２．１８（１Ｈ，ｄｄ，Ｊ＝１６．２Ｈｚ，１４．３Ｈｚ），１，８７−１．７３（３Ｈ，ｍ），１．６３−１．５１（１Ｈ，ｍ），１．１４（３Ｈ，ｄ，Ｊ＝６．６Ｈｚ），１．０６（３Ｈ，ｓ），０．１０（９Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.44-4.38 (2H, m), 3.97 (1H, dd, J = 10.2 Hz, 3.7 Hz), 3.92 (1H, dd, J = 10.7 Hz, 7.9 Hz), 2.65-2.58 (1H, m), 2.47-2.34 (1H, m), 2, 33 (1H, ddd, J = 16 .2 Hz, 6.3 Hz, 1.9 Hz), 2.18 (1 H, dd, J = 16.2 Hz, 14.3 Hz), 1,87-1.73 (3 H, m), 1.63-1. 51 (1H, m), 1.14 (3H, d, J = 6.6 Hz), 1.06 (3H, s), 0.10 (9H, s)

＜化合物２５の合成＞
化合物２４（７１．４ｍｇ、０．１９ｍｍｏｌ）に四塩化炭素（４００μＬ）とアセトニトリル（４００μＬ）、水（６００μＬ）を加え、さらに、室温で過ヨウ素酸ナトリウム（１７３．５ｍｇ、０．８１ｍｍｏｌ）を加え、溶解させた。さらに、室温で塩化ルテニウム（３．５ｍｇ、０．０２ｍｍｏｌ）を加え、室温で１３時間撹拌した。さらに、室温で過ヨウ素酸ナトリウム（８５．０ｍｇ、０．４０ｍｍｏｌ）、塩化ルテニウム（極少量）を追加し、２時間撹拌した。０℃でイソプロパノール（５００．０μＬ、６．５ｍｍｏｌ）を加え、クエンチした。さらに、飽和炭酸水素ナトリウム水溶液と酢酸エチルを加え、飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝５：１、体積比）で精製し、白色結晶として目的化合物（下記構造式２５で表される化合物２５、７１．２ｍｇ、収率９５．４％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 25>
Compound 24 (71.4 mg, 0.19 mmol) was added with carbon tetrachloride (400 μL), acetonitrile (400 μL) and water (600 μL), and sodium periodate (173.5 mg, 0.81 mmol) was added at room temperature. , Dissolved. Furthermore, ruthenium chloride (3.5 mg, 0.02 mmol) was added at room temperature, and the mixture was stirred at room temperature for 13 hours. Furthermore, sodium periodate (85.0 mg, 0.40 mmol) and ruthenium chloride (very small amount) were added at room temperature, and the mixture was stirred for 2 hours. Quenched by adding isopropanol (500.0 μL, 6.5 mmol) at 0 ° C. Further, a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added, washed once with a saturated aqueous sodium hydrogen carbonate solution and once with a saturated saline solution, the organic layer was dried over anhydrous sodium sulfate, and the desiccant was removed by filtration. Concentrated. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 5: 1, volume ratio), and the target compound (compound 25 represented by the following structural formula 25, 71.2 mg, yield 95.) as white crystals. 4%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．４５−４．３０（２Ｈ，ｍ），３．０８−３．０２（１Ｈ，ｍ），２．６５−２．４８（１Ｈ，ｍ），２．６５−２．４８（２Ｈ，ｍ），２．１０−１．７６（５Ｈ，ｍ），１．３８（３Ｈ，ｄ，Ｊ＝６．６Ｈｚ），１．２６（３Ｈ，ｓ），０．１２（９Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.45-4.30 (2H, m), 3.08-3.02 (1H, m), 2.65-2.48 (1H, m) , 2.65-2.48 (2H, m), 2.10-1.76 (5H, m), 1.38 (3H, d, J = 6.6 Hz), 1.26 (3H, s) , 0.12 (9H, s)

＜化合物２６の合成＞
化合物２５（５０．３ｍｇ、０．１１ｍｍｏｌ）をテトラヒドロフランに溶解させ、室温でセスキ炭酸ナトリウム二水和物（１２３．６ｍｇ、０．５５ｍｍｏｌ）を加えた。さらに室温でメタノール（８００μＬ）を加え、１時間撹拌した。０℃で飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝２：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式２６で表される化合物２６、３４．１ｍｇ、収率９４．２％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 26>
Compound 25 (50.3 mg, 0.11 mmol) was dissolved in tetrahydrofuran, and sodium sesquicarbonate dihydrate (123.6 mg, 0.55 mmol) was added at room temperature. Further, methanol (800 μL) was added at room temperature and stirred for 1 hour. Quenched by adding saturated aqueous ammonium chloride at 0 ° C. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous solution of ammonium chloride and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1, volume ratio), and the target compound (compound 26 represented by the following structural formula 26, 34.1 mg, yield) was obtained as a colorless transparent oil. 94.2%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：３．６８−３．６４（２Ｈ，ｍ），３．０９−３．０６（１Ｈ，ｍ），２．６２−２．４８（２Ｈ，ｍ），２．１０−２，００（１Ｈ，ｍ），１．８３−１．６２（４Ｈ，ｍ），１．３８（３Ｈ，ｄ，Ｊ＝６．６Ｈｚ），１．２７（３Ｈ，ｓ），０．１３（９Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 3.68-3.64 (2H, m), 3.09-3.06 (1H, m), 2.62-2.48 (2H, m) , 2.10-2, 00 (1H, m), 1.83-1.62 (4H, m), 1.38 (3H, d, J = 6.6 Hz), 1.27 (3H, s) , 0.13 (9H, s)

＜化合物２７の合成＞
塩化オキサリル・ジクロロメタン溶液（３７０μＬ、０．７４ｍｍｏｌ）を室温でジクロロメタン（５００μＬ）に加え、−７０℃に冷却した。そこに、ジクロロメタン（５００μＬ）に溶解させたジメチルスルホキシド（１０５μＬ、１．４８ｍｍｏｌ）を−７０℃で加え、３０分間撹拌した。トルエンと共沸させ脱水した化合物２６（７７．８ｍｇ、０．２５ｍｍｏｌ）をジクロロメタン（１．２ｍＬ）に溶解させ、−７０℃で加え、３０分間撹拌した。さらに、−７０℃でトリエチルアミン（２６０μＬ、１．８６ｍｍｏｌ）を加え３０分間撹拌した。−４０℃で水を加え、クエンチした。室温まで昇温させ酢酸エチルを加え、０．５規定塩酸で１回、飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式２７で表される化合物２７、７４．３ｍｇ、収率９６．１％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 27>
Oxalyl chloride / dichloromethane solution (370 μL, 0.74 mmol) was added to dichloromethane (500 μL) at room temperature and cooled to −70 ° C. Dimethyl sulfoxide (105 μL, 1.48 mmol) dissolved in dichloromethane (500 μL) was added thereto at −70 ° C. and stirred for 30 minutes. Compound 26 (77.8 mg, 0.25 mmol) azeotroped with toluene and dehydrated was dissolved in dichloromethane (1.2 mL), added at −70 ° C., and stirred for 30 minutes. Further, triethylamine (260 μL, 1.86 mmol) was added at −70 ° C. and stirred for 30 minutes. Water was added at -40 ° C to quench. Warm up to room temperature, add ethyl acetate, wash once with 0.5 N hydrochloric acid, once with saturated aqueous sodium bicarbonate, and once with saturated brine, dry the organic layer over anhydrous sodium sulfate, and filter to remove desiccant. Was removed, followed by concentration under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1, volume ratio), and the target compound (compound 27 represented by the following structural formula 27, 74.3 mg, yield) was obtained as a colorless transparent oil. 96.1%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：９．８０（１Ｈ，ｔ，Ｊ＝１．０Ｈｚ），３．１０−３．０７（１Ｈ，ｍ），２．７２−２．４８（４Ｈ，ｍ），２．１３−１．９３（３Ｈ，ｍ），１．３８（，ｄ，Ｊ＝６．６Ｈｚ），１．２５（３Ｈ，ｓ），０．１３（９Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 9.80 (1H, t, J = 1.0 Hz), 3.10-3.07 (1H, m), 2.72-2.48 (4H, m), 2.13-1.93 (3H, m), 1.38 (, d, J = 6.6 Hz), 1.25 (3H, s), 0.13 (9H, s)

＜化合物２８の合成＞
トルエンと共沸させ脱水した化合物２７（１３ｍｇ、０．０４ｍｍｏｌ）をテトラヒドロフラン（９００μＬ）に溶解させ、−７８℃で臭化イソプロピルマグネシウム・テトラヒドロフラン溶液（１２５μＬ、０．０６ｍｍｏｌ）を加え、−７８℃で３０分間撹拌した。０℃で飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝４：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式２８で表される化合物２８、１１．２ｍｇ、収率７５．７％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 28>
Compound 27 (13 mg, 0.04 mmol) azeotropically dehydrated with toluene was dissolved in tetrahydrofuran (900 μL), isopropylmagnesium bromide / tetrahydrofuran solution (125 μL, 0.06 mmol) was added at −78 ° C., and −78 ° C. Stir for 30 minutes. Quenched by adding saturated aqueous ammonium chloride at 0 ° C. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous solution of ammonium chloride and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1, volume ratio), and the target compound (compound 28 represented by the following structural formula 28, 11.2 mg, yield) was obtained as a colorless transparent oil. 75.7%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．９５−４．９３（１Ｈ，ｍ），４．８７−４．８４（１Ｈ，ｍ），４．０７−４．０２（１Ｈ，ｍ），３．１０−３．０５（１Ｈ，ｍ），２．７２−２．４７（２Ｈ，ｍ），２．１０−１．９５（１Ｈ，ｍ），１．９０−１．５５（４Ｈ，ｍ），１．７２（３Ｈ，ｓ），１．３８（３Ｈ，ｄ，Ｊ＝６．６Ｈｚ），１．２６（３Ｈ，ｓ），０．１３（９Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.95-4.93 (1H, m), 4.87-4.84 (1H, m), 4.07-4.02 (1H, m) 3.10-3.05 (1H, m), 2.72-2.47 (2H, m), 2.10-1.95 (1H, m), 1.90-1.55 (4H, m), 1.72 (3H, s), 1.38 (3H, d, J = 6.6 Hz), 1.26 (3H, s), 0.13 (9H, s)

＜化合物２９の合成＞
化合物２８（４０．８ｍｇ、０．１２ｍｍｏｌ）をエチルビニルエーテル（２．５ｍＬ）に溶解させ、室温で酢酸水銀（１８．４ｍｇ、０．０６ｍｍｏｌ）を加え、３０℃に加熱し、２３時間撹拌した。さらに室温で酢酸水銀（１８．５ｍｇ、０．０６ｍｍｏｌ）を追加し、３０℃で２４時間撹拌した。０℃で飽和炭酸水素ナトリウム水溶液を加えクエンチした。酢酸エチルを加え、飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物を、ショートカラムクロマトグラフィーにより残留試薬を除去後、粗生成物（下記構造式２９で表される化合物２９）を次の反応に用いた。 <Synthesis of Compound 29>
Compound 28 (40.8 mg, 0.12 mmol) was dissolved in ethyl vinyl ether (2.5 mL), mercury acetate (18.4 mg, 0.06 mmol) was added at room temperature, heated to 30 ° C., and stirred for 23 hours. Further, mercury acetate (18.5 mg, 0.06 mmol) was added at room temperature, and the mixture was stirred at 30 ° C. for 24 hours. The reaction was quenched by adding saturated aqueous sodium hydrogen carbonate solution at 0 ° C. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous sodium hydrogen carbonate solution and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. After removing the residual reagent from the crude product by short column chromatography, the crude product (Compound 29 represented by Structural Formula 29 below) was used in the next reaction.

＜化合物３０の合成＞
化合物２９の合成における粗生成物をキシレン（２ｍＬ）に溶解させ１３０℃に加熱し２時間撹拌した。減圧濃縮によりキシレンを留去した後、粗生成物（下記構造式３０で表される化合物３０）を次の反応に用いた。 <Synthesis of Compound 30>
The crude product in the synthesis of Compound 29 was dissolved in xylene (2 mL), heated to 130 ° C. and stirred for 2 hours. After distilling off xylene by concentration under reduced pressure, the crude product (compound 30 represented by the following structural formula 30) was used in the next reaction.

＜化合物３１の合成＞
水素化ホウ素ナトリウム（１６．０ｍｇ、０．３９ｍｍｏｌ）とテトラヒドロフラン（１．０ｍＬ）の混合液に、酢酸（２２０μＬ、３．８８ｍｍｏｌ）を加えて１５分間撹拌し、試薬を調製した。化合物３０の合成における粗生成物をテトラヒドロフラン（１．５ｍＬ）に溶解させ、調製した試薬（６１０μＬ、０．１９ｍｍｏｌ）を加え、１時間撹拌した。さらに、調製した試薬（３００μＬ、０．１０ｍｍｏｌ）を加え３０分間撹拌した。さらに、調製した試薬（３００μＬ、０．１０ｍｍｏｌ）を加え３０分間撹拌した。調製した試薬（４５０μＬ、０．１５ｍｍｏｌ）を加え３０分間撹拌した。０℃で飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式３１で表される化合物３１、３０．３ｍｇ、収率８１．７％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 31>
Acetic acid (220 μL, 3.88 mmol) was added to a mixed solution of sodium borohydride (16.0 mg, 0.39 mmol) and tetrahydrofuran (1.0 mL), and the mixture was stirred for 15 minutes to prepare a reagent. The crude product in the synthesis of Compound 30 was dissolved in tetrahydrofuran (1.5 mL), the prepared reagent (610 μL, 0.19 mmol) was added, and the mixture was stirred for 1 hour. Further, the prepared reagent (300 μL, 0.10 mmol) was added and stirred for 30 minutes. Further, the prepared reagent (300 μL, 0.10 mmol) was added and stirred for 30 minutes. The prepared reagent (450 μL, 0.15 mmol) was added and stirred for 30 minutes. Quenched by adding saturated aqueous ammonium chloride at 0 ° C. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous solution of ammonium chloride and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1, volume ratio) to give the target compound (compound 31, represented by the following structural formula 31, 30.3 mg, yield) as a colorless transparent oil. 81.7%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：５．１２（１Ｈ，ｔｄ，７．０Ｈｚ，１．２Ｈｚ），３．６３（２Ｈ，ｔ，Ｊ＝３．１Ｈｚ），３．１０−３．０５（１Ｈ，ｍ），２．６０−２．４７（２Ｈ，ｍ），２．２２−２．００（５Ｈ，ｍ），１．７５−１．６０（７Ｈ，ｍ），１．３９（３Ｈ，ｄ，Ｊ＝６．６Ｈｚ），１．２７（３Ｈ，ｓ），０．１３（９Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 5.12 (1H, td, 7.0 Hz, 1.2 Hz), 3.63 (2H, t, J = 3.1 Hz), 3.10-3. 05 (1H, m), 2.60-2.47 (2H, m), 2.22-2.00 (5H, m), 1.75-1.60 (7H, m), 1.39 ( 3H, d, J = 6.6 Hz), 1.27 (3H, s), 0.13 (9H, s)

＜化合物３２の合成＞
化合物３１（３．０ｍｇ、０．００７８ｍｍｏｌ）をジクロロメタン（８００μＬ）に溶解させ、室温でトリフルオロ酢酸（４００μＬ）を加え３０分間撹拌した。そのまま減圧濃縮し、粗生成物（下記構造式３２で表される化合物３２）を次の反応へ用いた。 <Synthesis of Compound 32>
Compound 31 (3.0 mg, 0.0078 mmol) was dissolved in dichloromethane (800 μL), trifluoroacetic acid (400 μL) was added at room temperature, and the mixture was stirred for 30 minutes. As it was concentrated under reduced pressure, the crude product (compound 32 represented by the following structural formula 32) was used for the next reaction.

＜化合物１の合成＞
フッ化テトラブチルアンモニウム・テトラヒドロフラン溶液（１００μＬ、０．１０ｍｍｏｌ）と酢酸（６．０μＬ、０．１０ｍｍｏｌ）の混合液を調製した。化合物３２の合成における粗生成物をテトラヒドロフラン（５００μＬ）に溶解させ、調製した試薬（２５μＬ、０．０２３ｍｍｏｌ）を室温で加え、３０分間撹拌した。そのまま減圧濃縮し、粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：２、体積比）で精製し、無色透明油状物として目的化合物（下記構造式１で表される化合物１、２．１ｍｇ、収率８３．３％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 1>
A mixed solution of tetrabutylammonium fluoride / tetrahydrofuran solution (100 μL, 0.10 mmol) and acetic acid (6.0 μL, 0.10 mmol) was prepared. The crude product in the synthesis of Compound 32 was dissolved in tetrahydrofuran (500 μL), the prepared reagent (25 μL, 0.023 mmol) was added at room temperature, and the mixture was stirred for 30 minutes. Concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 2, volume ratio) to give the target compound (compounds 1, 2 represented by the following structural formula 1 as a colorless transparent oil). 0.1 mg, yield 83.3%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：３．８６−３．７５（２Ｈ．ｍ），３．１７−３．１２（１Ｈ，ｍ），２．８９（１Ｈ，ｂｓ），２．５９−２．４７（２Ｈ，ｍ），２．２３−２．１４（１Ｈ，ｍ），１．９８−１．８３（２Ｈ，ｍ），１．８０−１．４５（８Ｈ，ｍ），１．４０（３Ｈ，ｄ，Ｊ＝６．６Ｈｚ），１．２４（３Ｈ，ｓ），１．１７（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 3.86-3.75 (2H.m), 3.17-3.12 (1H, m), 2.89 (1H, bs), 2.59 -2.47 (2H, m), 2.23-2.14 (1H, m), 1.98-1.83 (2H, m), 1.80-1.45 (8H, m), 1 .40 (3H, d, J = 6.6 Hz), 1.24 (3H, s), 1.17 (3H, s)

〔反応式（１）−１〕
[Reaction Formula (1) -1]

〔反応式（１）−２〕
[Reaction Formula (1) -2]

ここで、前記反応式（１）−１及び反応式（１）−２中、Ａｃはアセチルを表し、Ｂｕはブチルを表し、ＤＣＣはジシクロヘキシルカルボジイミドを表し、ＤＭＡＰはＮ，Ｎ−ジメチル−４−アミノピリジンを表し、ＤＭＦはＮ，Ｎ−ジメチルホルムアミドを表し、ＤＭＳＯはジメチルスルホキシドを表し、Ｅｔはエチルを表し、ＩＢＸは２−ヨードキシ安息香酸を表し、Ｍｅはメチルを表し、ＭＰＭは４−メトキシフェニルメチルを表し、ＰＴＳＡはｐ−トルエンスルホン酸を表し、ＴＢＡＦはフッ化テトラブチルアンモニウムを表し、ＴＢＳはＴｅｒｔ−ブチルジメチルシリルを表し、ＴＨＦはテトラヒドロフランを表し、ＴＭＳはトリメチルシリルを表し、Ｔｆ２Ｏはトリフルオロメタンスルホン酸無水物を表す。 In the reaction formulas (1) -1 and (1) -2, Ac represents acetyl, Bu represents butyl, DCC represents dicyclohexylcarbodiimide, and DMAP represents N, N-dimethyl-4- Represents aminopyridine, DMF represents N, N-dimethylformamide, DMSO represents dimethyl sulfoxide, Et represents ethyl, IBX represents 2-iodoxybenzoic acid, Me represents methyl, MPM represents 4-methoxy Represents phenylmethyl, PTSA represents p-toluenesulfonic acid, TBAF represents tetrabutylammonium fluoride, TBS represents Tert-butyldimethylsilyl, THF represents tetrahydrofuran, TMS represents trimethylsilyl, Tf 2 O Represents trifluoromethanesulfonic anhydride.

なお、前記反応式（１）−１及び反応式（１）−２中、化合物１１までの合成は、文献「Ｊ．Ｏｒｇ．Ｃｈｅｍ．，１９８７，５２，３３３７．」にて報告されている。また、化合物１１から１２の誘導は、文献「Ｔｅｔｒａｈｅｄｒｏｎ，２００８，６４，１１３１３．」に報告されている。
また、化合物２１ａ及び化合物２１ｂまでの合成は、「第５７回香料・テルペンおよび精油化学に関する討論会」（平成２５年１０月５日〜７日，埼玉大学）の講演要旨集ｐ．２８０−２８２にて公表されている。 In addition, in the reaction formulas (1) -1 and (1) -2, the synthesis up to the compound 11 is reported in the document “J. Org. Chem., 1987, 52, 3337.”. The induction of compounds 11 to 12 is reported in the document “Tetrahedron, 2008, 64, 11313.”.
In addition, the synthesis to compound 21a and compound 21b is described in “Summary of the 57th Discussion on Fragrance, Terpene and Essential Oil Chemistry” (October 5-7, 2013, Saitama University) p. 280-282.

（合成例２：化合物２の合成）
下記反応式（２）に示す通り、化合物２の合成を行った。 (Synthesis Example 2: Synthesis of Compound 2)
As shown in the following reaction formula (2), compound 2 was synthesized.

＜化合物３３の合成＞
化合物２５（１３．３ｍｇ、０．０２９ｍｍｏｌ）をテトラヒドロフラン（１．２ｍＬ）に溶解させ、乳鉢で擂り潰した炭酸水素ナトリウム（４９．１ｍｇ、０．５７９ｍｍｏｌ）、乳鉢で擂り潰した炭酸カリウム（２０．０ｍｇ、０．１４５ｍｍｏｌ）を室温で加え、さらに水（１１６μＬ）を加えた。さらにメタノール（５８０μ）を加え、１時間撹拌した。０℃で飽和塩化アンモニウム水溶液を加えクエンチした。酢酸エチルを加え、飽和塩化アンモニウム水溶液で１回、飽和食塩水で１回洗浄し、、水層を酢酸エチルで１回逆抽出した。有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝１：１、体積比）、（ヘキサン：酢酸エチル＝１：２、体積比）で精製した後、目的化合物として無色透明油状物（下記構造式２６で表される化合物２６、８．０ｍｇ、収率８４．０％）、副生成物として無色透明油状物（下記構造式３３で表される化合物３３、１．９ｍｇ、２７．１％）をそれぞれ得た。以下に、得られた化合物３３の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 33>
Compound 25 (13.3 mg, 0.029 mmol) was dissolved in tetrahydrofuran (1.2 mL), sodium hydrogen carbonate (49.1 mg, 0.579 mmol) ground in a mortar, and potassium carbonate (20. 0 mg, 0.145 mmol) was added at room temperature and more water (116 μL) was added. Further, methanol (580 μ) was added and stirred for 1 hour. Quenched by adding saturated aqueous ammonium chloride at 0 ° C. Ethyl acetate was added, washed once with a saturated aqueous ammonium chloride solution and once with a saturated saline solution, and the aqueous layer was back extracted once with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the desiccant was removed by filtration, followed by concentration under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1, volume ratio), (hexane: ethyl acetate = 1: 2, volume ratio), and then colorless and transparent oily substance (the following structure) Compound 26 represented by formula 26, 8.0 mg, yield 84.0%), colorless transparent oil as a by-product (compound 33 represented by the following structural formula 33, 1.9 mg, 27.1%) Respectively. The instrumental analysis value of 1 H-NMR of the obtained compound 33 is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：３．７０−３．６２（２Ｈ，ｍ），３．１７−３．１２（１Ｈ，ｍ），２．６０−２．５０（２Ｈ，ｍ），２．２３−２．１５（１Ｈ，ｍ），１．９０−１．６３（４Ｈ，ｍ），１．４０（３Ｈ，ｄ，Ｊ＝６．６Ｈｚ），１．２５（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 3.70-3.62 (2H, m), 3.17-3.12 (1H, m), 2.60-2.50 (2H, m) , 2.23-2.15 (1H, m), 1.90-1.63 (4H, m), 1.40 (3H, d, J = 6.6 Hz), 1.25 (3H, s)

＜化合物２の合成＞
化合物３３（３．３ｍｇ、０．０１３６ｍｍｏｌ）をＮ，Ｎ−ジメチルホルムアミド（５００μＬ）に溶解させ、室温でピリジン（１１μＬ、０．１３６ｍｍｏｌ）を加え、さらに室温で無水酢酸（１３μＬ、０．１３６ｍｍｏｌ）を加え、Ｎ，Ｎ−ジメチル−４−アミノピリジン（極少量）を加え、３０分間撹拌した。０℃で飽和炭酸水素ナトリウム水溶液を加えクエンチした。酢酸エチルを加え、飽和炭酸水素ナトリウム水溶液で１回、飽和食塩水で１回洗浄し、有機層を無水硫酸ナトリウムで乾燥させろ過により乾燥剤を除去した後、減圧濃縮した。粗生成物を、シリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝１：１、体積比）で精製し、無色透明油状物として目的化合物（下記構造式２で表される化合物２、２．５ｍｇ、収率６５．８％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 2>
Compound 33 (3.3 mg, 0.0136 mmol) was dissolved in N, N-dimethylformamide (500 μL), pyridine (11 μL, 0.136 mmol) was added at room temperature, and acetic anhydride (13 μL, 0.136 mmol) was further added at room temperature. N, N-dimethyl-4-aminopyridine (very small amount) was added and stirred for 30 minutes. The reaction was quenched by adding saturated aqueous sodium hydrogen carbonate solution at 0 ° C. Ethyl acetate was added, and the mixture was washed once with a saturated aqueous sodium hydrogen carbonate solution and once with a saturated saline solution. The organic layer was dried over anhydrous sodium sulfate, filtered to remove the desiccant, and then concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1, volume ratio) to obtain the target compound (compound 2, represented by the following structural formula 2, 2.5 mg as a colorless transparent oil). 65.8%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤＣｌ３）δ：４．０８（２Ｈ，ｔ，Ｊ＝６．２Ｈｚ），３．１６−３．１３（１Ｈ，ｍ），２．８０（１Ｈ，ｂｓ），２．６０−２．５０（２Ｈ，ｍ），２．２５−２．１０（１Ｈ，ｍ），２．０５（３Ｈ，ｓ），１．９０−１．７０（４Ｈ，ｍ），１．４０（３Ｈ，ｄ，Ｊ＝６．６Ｈｚ），１．２５（３Ｈ，ｓ） 1 H-NMR (400 MHz, CDCl 3 ) δ: 4.08 (2H, t, J = 6.2 Hz), 3.16-3.13 (1H, m), 2.80 (1H, bs), 2 .60-2.50 (2H, m), 2.25-2.10 (1H, m), 2.05 (3H, s), 1.90-1.70 (4H, m), 1.40 (3H, d, J = 6.6 Hz), 1.25 (3H, s)

〔反応式（２）〕
[Reaction Formula (2)]

ここで、前記反応式（２）中、Ａｃはアセチルを表し、ＤＭＡＰはＮ，Ｎ−ジメチル−４−アミノピリジンを表し、ＤＭＦはＮ，Ｎ−ジメチルホルムアミドを表し、Ｍｅはメチルを表し、ＴＨＦはテトラヒドロフランを表し、ＴＭＳはトリメチルシリルを表す。   Here, in the reaction formula (2), Ac represents acetyl, DMAP represents N, N-dimethyl-4-aminopyridine, DMF represents N, N-dimethylformamide, Me represents methyl, THF Represents tetrahydrofuran, and TMS represents trimethylsilyl.

（合成例３：化合物３の合成）
下記反応式（３）に示す通り、化合物３の合成を行った。 (Synthesis Example 3: Synthesis of Compound 3)
Compound 3 was synthesized as shown in the following reaction formula (3).

＜化合物３の合成＞
フッ化テトラブチルアンモニウム・テトラヒドロフラン溶液（１０５μＬ、０．１０ｍｍｏｌ）と酢酸（６．０μＬ、０．１０ｍｍｏｌ）の混合液を調製した。化合物３１（５．３ｍｇ、０．０１ｍｍｏｌ）をテトラヒドロフラン（９５０μＬ）に溶解させ、調製した試薬（４５μＬ、０．０４ｍｍｏｌ）を室温で加え、３０分間撹拌した。そのまま減圧濃縮し、粗生成物をシリカゲルカラムクロマトグラフィー（ヘキサン：酢酸エチル＝３：２）で精製し、無色透明油状物として目的化合物（下記構造式３で表される化合物３、４．４ｍｇ、収率１００％）を得た。以下に、得られた化合物の１Ｈ−ＮＭＲの機器分析値を示す。 <Synthesis of Compound 3>
A mixed solution of tetrabutylammonium fluoride / tetrahydrofuran solution (105 μL, 0.10 mmol) and acetic acid (6.0 μL, 0.10 mmol) was prepared. Compound 31 (5.3 mg, 0.01 mmol) was dissolved in tetrahydrofuran (950 μL), the prepared reagent (45 μL, 0.04 mmol) was added at room temperature, and the mixture was stirred for 30 minutes. Concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 2) to give the target compound (compound 3, 4.4 mg represented by the following structural formula 3 as a colorless transparent oil) Yield 100%). The instrumental analysis value of 1 H-NMR of the obtained compound is shown below.

１Ｈ−ＮＭＲ（４００ＭＨｚ，ＣＤ３ＯＤ）δ：５．１７（１Ｈ，ｔｑ，７．２Ｈｚ，１．２Ｈｚ），４．６０（１Ｈ，ｂｓ），３．５１（２Ｈ，ｔ，Ｊ＝６．６Ｈｚ），３．１４（１Ｈ，ｄｄ，Ｊ＝７．７Ｈｚ，１，５Ｈｚ），
２．６０−２．５５（１Ｈ，ｍ），２．５０−２．４５（１Ｈ，ｍ），２．３０−２．００（５Ｈ，ｍ），１．７６−１．７２（１Ｈ，ｍ），１．６５−１．５７（６Ｈ，ｍ）１．３４（３Ｈ，ｄ，Ｊ＝６．９Ｈｚ），１．２７（３Ｈ，ｓ） 1 H-NMR (400 MHz, CD 3 OD) δ: 5.17 (1H, tq, 7.2 Hz, 1.2 Hz), 4.60 (1H, bs), 3.51 (2H, t, J = 6) .6 Hz), 3.14 (1 H, dd, J = 7.7 Hz, 1, 5 Hz),
2.60-2.55 (1H, m), 2.50-2.45 (1H, m), 2.30-2.00 (5H, m), 1.76-1.72 (1H, m ), 1.65-1.57 (6H, m) 1.34 (3H, d, J = 6.9 Hz), 1.27 (3H, s)

〔反応式（３）〕
[Reaction Formula (3)]

ここで、前記反応式（３）中、Ａｃはアセチルを表し、ＴＢＡＦはフッ化テトラブチルアンモニウムを表し、ＴＨＦはテトラヒドロフランを表し、ＴＭＳはトリメチルシリルを表す。   In the reaction formula (3), Ac represents acetyl, TBAF represents tetrabutylammonium fluoride, THF represents tetrahydrofuran, and TMS represents trimethylsilyl.

（調製例１）
＜性刺激剤ａの調製＞
雌鞘翅に含まれる合成炭化水素８成分として、ヘプタコサン７ｍｇ、ノナコサン２．７ｍｇ、４−メチルヘキサコサン８ｍｇ、４−メチルオクタコサン１２．８ｍｇ、９−メチルヘプタコサン６．６ｍｇ、９−メチルノナコサン６．７ｍｇ、１５−メチルヘントリアコンタン６．８ｍｇ、及び１５−メチルヘントリトリアコンタン４．６ｍｇと、合成ケトン３成分として、ヘプタコサン−１０−オン２５ｍｇ、及び（１８Ｚ）−ヘプタコセン−１０−オン４０μｇ、（１８Ｚ，２１Ｚ）−ヘプタコサジエン−１０−オン１００μｇとを、ヘキサン５ｍＬ中に含まれるように混合して性刺激剤ａを調製した。
直径１２ｍｍ、長さ３５ｍｍで両端を丸めた黒ガラス棒の表面に、５０μＬの性刺激剤ａ（雌１頭分に相当）を塗布し、後述する比較例１の性刺激活性試験に用いる試料とした。 (Preparation Example 1)
<Preparation of Sexual Stimulant a>
As 8 components of synthetic hydrocarbons contained in female sheath pods, heptacosan 7 mg, nonacosan 2.7 mg, 4-methylhexacosane 8 mg, 4-methyloctacosane 12.8 mg, 9-methylheptacosane 6.6 mg, 9-methylnonacosan 6.7 mg, 15-methylhentriacontan 6.8 mg, and 15-methylhentriatritan 4.6 mg, heptacosane-10-one 25 mg, and (18Z) -heptacosen-10-one as three synthetic ketone components Sex stimulant a was prepared by mixing 40 μg, (18Z, 21Z) -heptacosadien-10-one 100 μg so as to be contained in 5 mL of hexane.
50 μL of sex stimulant a (corresponding to one female) was applied to the surface of a black glass rod having a diameter of 12 mm and a length of 35 mm rounded at both ends, and a sample used for the sex stimulating activity test of Comparative Example 1 described later. did.

（調製例２）
＜性刺激剤ｂの調製＞
直径１２ｍｍ、長さ３５ｍｍで両端を丸めた黒ガラス棒の表面に、５０μＬの性刺激剤ａと、以下の通り調製したメス粗抽出物（雌１頭分）とを混合塗布して、ポジティブコントロールとしての性刺激剤ｂ、及び性刺激剤ｂを塗布した試料を調製した。 (Preparation Example 2)
<Preparation of sex stimulant b>
On the surface of a black glass rod with a diameter of 12 mm and a length of 35 mm rounded at both ends, 50 μL of sex stimulant a and a female crude extract (one female) prepared as follows were mixed and applied to make a positive control. As a sex stimulant b, and a sample coated with the sex stimulant b.

−雌粗抽出物の調製−
野外から採集したゴマダラカミキリの雌成虫５２８頭分の鞘翅をエーテル８００ｍＬで３回それぞれ５分間抽出し、抽出物を合わせた。抽出物をヘキサンに転溶し、雌粗抽出物を調製した。 -Preparation of female crude extract-
The pods of 528 adult females of the longhorn beetle collected from the field were extracted 3 times with 800 mL of ether for 5 minutes each, and the extracts were combined. The extract was dissolved in hexane to prepare a crude female extract.

（調製例３）
＜性刺激剤Ａの調製＞
直径１２ｍｍ、長さ３５ｍｍで両端を丸めた黒ガラス棒の表面に、５０μＬの性刺激剤ａと、合成例１で得られた化合物１ １μｇ（雌１頭分に相当）とを混合塗布して、性刺激剤Ａ、及び性刺激剤Ａを塗布した試料を調製した。 (Preparation Example 3)
<Preparation of sex stimulant A>
50 μL of sex stimulant a and 1 μg of compound 1 obtained in Synthesis Example 1 (corresponding to one female) were mixed and applied to the surface of a black glass rod having a diameter of 12 mm and a length of 35 mm rounded at both ends. , Sex stimulant A, and a sample coated with sex stimulant A were prepared.

（調製例４）
＜性刺激剤Ｂの調製＞
直径１２ｍｍ、長さ３５ｍｍで両端を丸めた黒ガラス棒の表面に塗布した１μｇの性刺激剤ａに、合成例２で得られた化合物２ １μｇ（雌１頭分に相当）とを混合塗布して、性刺激剤Ｂ、及び性刺激剤Ｂを塗布した試料を調製した。 (Preparation Example 4)
<Preparation of Sexual Stimulant B>
1 μg of the sex stimulant a applied to the surface of a black glass rod having a diameter of 12 mm and a length of 35 mm rounded at both ends was mixed and applied with 1 μg of the compound 2 obtained in Synthesis Example 2 (corresponding to one female). Then, sex stimulant B and a sample coated with sex stimulant B were prepared.

（調製例５）
＜性刺激剤Ｃの調製＞
直径１２ｍｍ、長さ３５ｍｍで両端を丸めた黒ガラス棒の表面に塗布した１μｇの性刺激剤ａに、合成例３で得られた化合物３ １μｇ（雌１頭分に相当）とを混合塗布して、性刺激剤Ｃ、及び性刺激剤Ｃを塗布した試料を調製した。 (Preparation Example 5)
<Preparation of Sexual Stimulant C>
1 μg of the sex stimulant a applied to the surface of a black glass rod having a diameter of 12 mm and a length of 35 mm rounded at both ends was mixed and applied with 1 μg of the compound 3 obtained in Synthesis Example 3 (corresponding to one female). Then, sex stimulant C and a sample coated with sex stimulant C were prepared.

（調製例６〜８）
＜性刺激剤Ｄ〜Ｆの調製＞
調製例３〜５において、化合物１〜３の混合量を１μｇ（雌１頭分に相当）から５μｇ（雌５頭分に相当）に変更した以外は、調製例３〜５と同様にして、調製例６〜８の性刺激剤Ｄ〜Ｆ、及び性刺激剤Ｄ〜Ｆを塗布した試料をそれぞれ調製した。 (Preparation Examples 6 to 8)
<Preparation of sex stimulants D to F>
In Preparation Examples 3 to 5, in the same manner as in Preparation Examples 3 to 5, except that the mixing amount of Compounds 1 to 3 was changed from 1 μg (corresponding to one female) to 5 μg (corresponding to five females), Samples to which sex stimulants D to F and sex stimulants D to F of Preparation Examples 6 to 8 were applied were prepared.

（実施例１）
直径１２ｍｍ、長さ３５ｍｍで両端を丸めた黒ガラス棒の表面に、１μｇの性刺激剤Ａを塗布した試料（調製例３）を用い、前記試料に触れたゴマダラカミキリの雄の腹曲げ行動を観察する検定法により、性刺激活性試験を行った。
具体的には、直径１５センチのろ紙（Ｎｏ．２、アドバンテック株式会社製）に前記試料１つを貼りつけ、別のろ紙に乗せたゴマダラカミキリの成体雄（１個体）の触角が試料に触れるように入れて、透明プラスチックカップ（直径１２ｃｍ×高さ１０ｃｍ）でカバーして５分間の行動を観察した。供試個体数に対して、腹曲げ行動が観察された個体数（反応個体数）の割合（％）、及び「反応個体数／供試個体数」を下記表１に示した。 Example 1
Using a sample (Preparation Example 3) in which 1 μg of sex stimulant A was applied to the surface of a black glass rod with a diameter of 12 mm and a length of 35 mm rounded at both ends, the abdominal bending behavior of a long-horned beetle male touching the sample was observed. The sexually stimulating activity test was conducted by the assay method.
Specifically, one sample is attached to a filter paper (No. 2, manufactured by Advantech Co., Ltd.) having a diameter of 15 centimeters, and the antennae of an adult male (one individual) of the spotted beetle placed on another filter paper touches the sample. And covered with a transparent plastic cup (diameter 12 cm × height 10 cm), and the behavior for 5 minutes was observed. Table 1 below shows the ratio (%) of the number of individuals in which abdominal bending behavior was observed (the number of responding individuals) and the “number of responding individuals / number of test individuals” with respect to the number of test individuals.

（実施例２〜６）
実施例１において、下記表１に示す通り、性刺激剤Ａを塗布した試料に代えて性刺激剤Ｂ〜Ｆを塗布した試料を用いた以外は、実施例１と同様にして、実施例２〜６を行った。結果を下記表１に示す。 (Examples 2 to 6)
In Example 1, as shown in Table 1 below, Example 2 was carried out in the same manner as in Example 1 except that samples applied with sexual stimulants B to F were used instead of the samples applied with sexual stimulant A. ~ 6 was performed. The results are shown in Table 1 below.

（比較例１〜２）
実施例１において、下記表１に示す通り、性刺激剤Ａを塗布した試料に代えて性刺激剤ａ〜ｂを塗布した試料を用いた以外は、実施例１と同様にして、ネガティブコントロールとなる比較例１、及びポジティブコントロールとなる比較例２を行った。結果を下記表１に示す。 (Comparative Examples 1-2)
In Example 1, as shown in Table 1 below, in the same manner as in Example 1 except that the sample coated with sexual stimulant ab was used instead of the sample coated with sexual stimulant A, Comparative Example 1 and Comparative Example 2 serving as a positive control were performed. The results are shown in Table 1 below.

Claims (13)

下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、３−オキサビシクロ［３．３．０］オクタン骨格の５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の３−オキサビシクロ［３．３．０］オクタン骨格の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基をアルデヒド基に置換し、下記構造式２７で表される化合物を生成させる工程と、
前記構造式２７で表される化合物のアルデヒド基を順次反応させて２−メチル−５−ヒドロキシ−１−ペンテニル基に置換し、下記構造式３１で表される化合物を生成させる工程と、
前記構造式３１で表される化合物の２−メチル−５−ヒドロキシ−１−ペンテニル基を環化し、トリメチルシリル基を水酸基に置換し、下記構造式１で表される化合物を生成させる工程と、を含み、
前記構造式３１で表される化合物を生成させる工程が、
脱水した前記構造式２７で表される化合物をテトラヒドロフランに溶解させ、臭化イソプロピルマグネシウム・テトラヒドロフラン溶液を加えて反応させ、下記構造式２８で表される化合物を生成させる処理と、
前記構造式２８で表される化合物をエチルビニルエーテルに溶解させ、酢酸水銀を加えて反応させ、下記構造式２９で表される化合物を生成させる処理と、
前記構造式２９で表される化合物をキシレンに溶解させ、加熱して反応させ、下記構造式３０で表される化合物を生成する処理と、
前記構造式３０で表される化合物をテトラヒドロフランに溶解させ、酢酸を加えた水素化ホウ素ナトリウムとテトラヒドロフランの混合液を加えて反応させ、前記構造式３１で表される化合物を生成させる処理と、を含むことを特徴とする下記構造式１で表される化合物の製造方法。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、２５、２７、２８、２９、３０、及び３１中、ＴＭＳはトリメチルシリルを表す。） The compound represented by the following structural formula 21b is hydrogen-substituted in the presence of a catalyst, the 4-methoxyphenylmethyl group is substituted with a trichloroacetyl group, and the 5-position of 3-oxabicyclo [3.3.0] octane skeleton is substituted. A step of producing a compound represented by the following structural formula 24 by protecting the hydroxyl group with a trimethylsilyl group;
Adding a oxo group to the 2-position of the 3-oxabicyclo [3.3.0] octane skeleton of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25 below;
Replacing the trichloroacetyl group of the compound represented by the structural formula 25 with an aldehyde group to form a compound represented by the following structural formula 27;
A step of sequentially reacting an aldehyde group of the compound represented by the structural formula 27 and substituting it with a 2-methyl-5-hydroxy-1-pentenyl group to form a compound represented by the following structural formula 31;
Cyclizing the 2-methyl-5-hydroxy-1-pentenyl group of the compound represented by Structural Formula 31 and substituting the trimethylsilyl group with a hydroxyl group to form a compound represented by Structural Formula 1 below. seen including,
Generating the compound represented by the structural formula 31;
A process of dissolving the dehydrated compound represented by the structural formula 27 in tetrahydrofuran, adding an isopropylmagnesium bromide-tetrahydrofuran solution to react to form a compound represented by the following structural formula 28;
A treatment of dissolving the compound represented by the structural formula 28 in ethyl vinyl ether, adding mercury acetate and reacting to form a compound represented by the following structural formula 29;
A process of dissolving the compound represented by the structural formula 29 in xylene and reacting by heating to produce a compound represented by the following structural formula 30;
Treating the compound represented by the structural formula 30 in tetrahydrofuran, adding a mixture of sodium borohydride to which acetic acid has been added and tetrahydrofuran, and reacting the mixture to form the compound represented by the structural formula 31; process for producing a compound represented by the following structural formula 1, wherein including Mukoto.
(In the structural formula 21b, MPM represents 4-methoxyphenylmethyl , and in the structural formulas 24 , 25 , 27 , 28 , 29, 30, and 31, TMS represents trimethylsilyl.) 下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、３−オキサビシクロ［３．３．０］オクタン骨格の５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の３−オキサビシクロ［３．３．０］オクタン骨格の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基を順次反応させてアセチル基に置換し、下記構造式２で表される化合物を生成させる工程と、を含み、
前記構造式２で表される化合物を生成させる工程が、
前記構造式２５で表される化合物をテトラヒドロフランに溶解させ、炭酸水素ナトリウム、炭酸カリウム、水、及びメタノールを加えて反応させ、下記構造式３３で表される化合物を生成させる処理と、
前記構造式３３で表される化合物をＮ，Ｎ−ジメチルホルムアミドに溶解させ、ピリジン、無水酢酸、及びＮ，Ｎ−ジメチル−４−アミノピリジンを加えて反応させ、前記構造式２で表される化合物を生成させる処理と、を含むことを特徴とする下記構造式２で表される化合物の製造方法。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、及び２５中、ＴＭＳはトリメチルシリルを表す。） The compound represented by the following structural formula 21b is hydrogen-substituted in the presence of a catalyst, the 4-methoxyphenylmethyl group is substituted with a trichloroacetyl group, and the 5-position of 3-oxabicyclo [3.3.0] octane skeleton is substituted. A step of producing a compound represented by the following structural formula 24 by protecting the hydroxyl group with a trimethylsilyl group;
Adding a oxo group to the 2-position of the 3-oxabicyclo [3.3.0] octane skeleton of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25 below;
The structural formula and sequentially reacting trichloroacetyl group of compounds represented by 25 is replaced with an acetyl group, seen containing a step of producing a compound represented by the following structural formula 2, a,
The step of generating the compound represented by Structural Formula 2 comprises:
Treatment for dissolving the compound represented by the structural formula 25 in tetrahydrofuran, adding sodium hydrogen carbonate, potassium carbonate, water and methanol and reacting them to produce a compound represented by the following structural formula 33;
The compound represented by Structural Formula 33 is dissolved in N, N-dimethylformamide, and reacted by adding pyridine, acetic anhydride, and N, N-dimethyl-4-aminopyridine, and represented by Structural Formula 2. method for producing a compound of the processing to produce a compound, the represented by the following structural formula 2, wherein including Mukoto.
(However, in Structural Formula 21b, MPM represents 4-methoxyphenylmethyl, and in Structural Formulas 24 and 25, TMS represents trimethylsilyl.) 下記構造式２１ｂで表される化合物を、触媒存在下で水素置換し、４−メトキシフェニルメチル基をトリクロロアセチル基に置換し、３−オキサビシクロ［３．３．０］オクタン骨格の５位の水酸基をトリメチルシリル基で保護することにより、下記構造式２４で表される化合物を生成させる工程と、
前記構造式２４で表される化合物の３−オキサビシクロ［３．３．０］オクタン骨格の２位にオキソ基を付与し、下記構造式２５で表される化合物を生成させる工程と、
前記構造式２５で表される化合物のトリクロロアセチル基をアルデヒド基に置換し、下記構造式２７で表される化合物を生成させる工程と、
前記構造式２７で表される化合物のアルデヒド基を順次反応させて２−メチル−５−ヒドロキシ−１−ペンテニル基に置換し、下記構造式３１で表される化合物を生成させる工程と、
前記構造式３１で表される化合物のトリメチルシリル基を水酸基に置換し、下記構造式３で表される化合物を生成させる工程と、を含み、
前記構造式３１で表される化合物を生成させる工程が、
脱水した前記構造式２７で表される化合物をテトラヒドロフランに溶解させ、臭化イソプロピルマグネシウム・テトラヒドロフラン溶液を加えて反応させ、下記構造式２８で表される化合物を生成させる処理と、
前記構造式２８で表される化合物をエチルビニルエーテルに溶解させ、酢酸水銀を加えて反応させ、下記構造式２９で表される化合物を生成させる処理と、
前記構造式２９で表される化合物をキシレンに溶解させ、加熱して反応させ、下記構造式３０で表される化合物を生成する処理と、
前記構造式３０で表される化合物をテトラヒドロフランに溶解させ、酢酸を加えた水素化ホウ素ナトリウムとテトラヒドロフランの混合液を加えて反応させ、前記構造式３１で表される化合物を生成させる処理と、を含むことを特徴とする下記構造式３で表される化合物の製造方法。
（ただし、前記構造式２１ｂ中、ＭＰＭは４−メトキシフェニルメチルを表し、前記構造式２４、２５、２７、２８、２９、３０、及び３１中、ＴＭＳはトリメチルシリルを表す。） The compound represented by the following structural formula 21b is hydrogen-substituted in the presence of a catalyst, the 4-methoxyphenylmethyl group is substituted with a trichloroacetyl group, and the 5-position of 3-oxabicyclo [3.3.0] octane skeleton is substituted. A step of producing a compound represented by the following structural formula 24 by protecting the hydroxyl group with a trimethylsilyl group;
Adding a oxo group to the 2-position of the 3-oxabicyclo [3.3.0] octane skeleton of the compound represented by Structural Formula 24 to form a compound represented by Structural Formula 25 below;
Replacing the trichloroacetyl group of the compound represented by the structural formula 25 with an aldehyde group to form a compound represented by the following structural formula 27;
A step of sequentially reacting an aldehyde group of the compound represented by the structural formula 27 and substituting it with a 2-methyl-5-hydroxy-1-pentenyl group to form a compound represented by the following structural formula 31;
The trimethylsilyl group of the compound represented by the structural formula 31 substituted with a hydroxyl group, seen including a step of producing a compound represented by the following structural formula 3, a,
Generating the compound represented by the structural formula 31;
A process of dissolving the dehydrated compound represented by the structural formula 27 in tetrahydrofuran, adding an isopropylmagnesium bromide-tetrahydrofuran solution to react to form a compound represented by the following structural formula 28;
A treatment of dissolving the compound represented by the structural formula 28 in ethyl vinyl ether, adding mercury acetate and reacting to form a compound represented by the following structural formula 29;
A process of dissolving the compound represented by the structural formula 29 in xylene and reacting by heating to produce a compound represented by the following structural formula 30;
Treating the compound represented by the structural formula 30 in tetrahydrofuran, adding a mixture of sodium borohydride to which acetic acid has been added and tetrahydrofuran, and reacting the mixture to form the compound represented by the structural formula 31; process for producing a compound represented by the following structural formula 3 wherein free Mukoto.
(In the structural formula 21b, MPM represents 4-methoxyphenylmethyl , and in the structural formulas 24 , 25 , 27 , 28 , 29, 30, and 31, TMS represents trimethylsilyl.) 下記構造式１で表されることを特徴とする化合物。
〔構造式１〕
A compound represented by the following structural formula 1.
[Structural formula 1]
下記構造式２で表されることを特徴とする化合物。
〔構造式２〕
A compound represented by the following structural formula 2.
[Structural formula 2]
下記構造式３で表されることを特徴とする化合物。
〔構造式３〕
A compound represented by the following structural formula 3.
[Structural formula 3]
下記構造式２２〜３３のいずれかで表される請求項４から６のいずれかに記載の化合物の中間体。
（ただし、前記構造式２４〜３２中、ＴＭＳはトリメチルシリルを表す。） The intermediate of the compound in any one of Claims 4-6 represented by either of following Structural formula 22-33.
(However, in the structural formulas 24-32, TMS represents trimethylsilyl.) 請求項４から６のいずれかに記載の化合物を有効成分として含むことを特徴とするゴマダラカミキリの性刺激剤。   A sex stimulant for longhorn beetle, comprising the compound according to any one of claims 4 to 6 as an active ingredient. ヘプタコサン、ノナコサン、４−メチルヘキサコサン、４−メチルオクタコサン、９−メチルヘプタコサン、９−メチルノナコサン、１５−メチルヘントリアコンタン、及び１５−メチルヘントリトリアコンタンからなる群から選ばれる少なくとも１種の炭化水素を更に含む請求項８に記載のゴマダラカミキリの性刺激剤。   At least selected from the group consisting of heptacosane, nonacosane, 4-methylhexacosane, 4-methyloctacosane, 9-methylheptacosan, 9-methylnonacosane, 15-methylhentriacontane, and 15-methylhentriatritan The sex stimulant for the longhorn beetle according to claim 8, further comprising one type of hydrocarbon. ヘプタコサン−１０−オン、（１８Ｚ）−ヘプタコセン−１０−オン、及び（１８Ｚ，２１Ｚ）−ヘプタコサジエン−１０−オンからなる群から選ばれる少なくとも１種のケトンを更に含む請求項８から９のいずれかに記載のゴマダラカミキリの性刺激剤。   10. The method according to claim 8, further comprising at least one ketone selected from the group consisting of heptacosane-10-one, (18Z) -heptacosen-10-one, and (18Z, 21Z) -heptacosadien-10-one. The sex stimulant for longhorn beetle described in 1. 基材に塗布又は含浸されてなる請求項８から１０のいずれかに記載のゴマダラカミキリの性刺激剤。   The sex stimulant for a long-horned beetle according to any one of claims 8 to 10, which is applied or impregnated on a base material. 請求項８から１１のいずれかに記載のゴマダラカミキリの性刺激剤を含むことを特徴とするゴマダラカミキリの防除剤。   A control agent for a long-horned beetle, comprising the sex stimulant for the long-horned beetle according to any one of claims 8 to 11. 殺虫成分を更に含む請求項１２に記載のゴマダラカミキリの防除剤。   The control agent for a long-horned beetle according to claim 12, further comprising an insecticidal component.
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