CN111362895A - Synthesis method of naphthofuran derivative, naphthofuran derivative and application - Google Patents
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Abstract
The invention belongs to the technical field of organic compounds and synthesis, and discloses a synthesis method of a naphthofuran derivative, the naphthofuran derivative and application thereof, wherein an o-furan aryl propargyl alcohol derivative and aryl boric acid are used as raw materials, and the reaction is carried out on furan aryl propargyl alcohol and aryl boric acid under Boc protection under the conditions of appropriate transition metal, additive, solvent and reaction temperature; obtaining the naphthofuran derivative shown in the formula (I). The invention also provides application of the naphthofuran derivatives in preparation of antibacterial, antitumor and antiviral active medicines. The preparation method has the advantages of cheap and easily obtained raw materials, high reaction yield, strong functional group tolerance, simple post-treatment, environmental friendliness and the like.
Description
Technical Field
The invention belongs to the technical field of organic compounds and synthesis, and particularly relates to a synthetic method of a naphthofuran derivative, the naphthofuran derivative and application of the naphthofuran derivative.
Background
At present, the naphthofuran skeleton exists in natural products or drug molecules with physiological activity in a large amount, and shows various biological activities, including antifungal activity, antibacterial drugs, insecticides, antiproliferative drugs, cytotoxic activity, antioxidant activity, anti-inflammatory activity, antitumor activity, nuclear receptor modulator HNF4 α, nicotinic acetylcholine receptor agonist (nAChR), etc.
At present, the synthesis method of the naphthofuran skeleton mainly comprises the following strategies: 1) cyclization of naphthylalkyne (ene) propyl ether (a) Lingam, v.s.p.; dahale, d.h.; mukkani, k.; gopalan, B.; thmas, a.; tetrahedron Lett,2012,53,5695.(b) Wang, w.; huang, j.; zhou, r.; jiang, z.j.; fu, h.y.; zheng, x.l.; chen, h.; li, r.x.adv.synth.catal.2015,357, 2442; 2) cyclization of 2-alkenylnaphthol/2-allylnaphthol (a) young, s.w.; eom, j.i.org.lett.2005,7,3355.(b) Pancote, c.g.; carvalho, b.s.; luchez, c.v.; fernandes, j.p.s.; politi, m.j.; brandt, c.a. synthesis,2009,3963(c) Rao, v.k.; shelke, g.m.; tiwari, r.; parang, k.; kumar, a.org.lett.2013,15,2190.(d) Yang, d.j.; zhu, y.f.; yang, n.; jiang, q.q.; liu, r.h.adv.synth.catl.2016, 358, 1731; 3) naphthol reaction with other active molecules including nitroolefin, propargyl alcohol, dibromoolefin, propargyl alcohol carbonate, alkyne, etc. (a) Rao, m.l.n.; dasgupta, p.rscadv.,2015,5,65462(b) Watanabe, h.; okubo, m.; watanabe, k.; udagawa, t.; kawatsura, m.tetrahedron lett,2017,58,2893(c) Kuram, m.r.; bhanduchandra, m.; sahoo, a.k.angelw.chem.int.ed.2013, 52,4607.(d) Zeng, w.; wu, w.q.; jiang, h.f.; huang, l.b.; sun, y.d.; chen, z.w.; li, x.w.chem.commun.,2013,49,6611.(e) Zhu, r.y.; wei, j.b.; shi, z.j.chem.sci.,2013,4,3706 (f) Liu, l.; ji, x.y.; dong, j.y.; zhou, y.b.; yin, s.f.org.lett.2016,18,3138; 4) cyclization of o-furan arylalkynes (a) Maeyama, K.; iwasawa, n.j.org.chem.1999,64,1344.(b) Byers, p.m.; rashed, j.i.; mohamed, r.k.; albugin, i.v. org.lett.2012,14,6032.(c) Yamamoto, y.; matsui, k.; shibuya, m.chem.eur.j.2015,21,7245. the first three strategies mostly involve naphthol or derivatives thereof as starting materials, with certain limitations.
The fourth strategy involves terminal alkyne, and needs to use W (CO) with high toxicity5Or noble metals Au/Ag, Ru, etc., and the reaction time of most reactions is longer and the temperature is higher. Therefore, there is still a need to enrich and develop a milder and more convenient synthetic method of naphthofuran derivatives.
Although the construction method of the naphthofuran skeleton has been reported, most reactions start from naphthol or functionalized derivatives thereof, and the substrate applicability is single. Designing an o-furan aryl alkyne substrate and constructing a naphthofuran derivative by utilizing a 6 pi electrocyclization strategy is also an important method. However, these reactions involve terminal alkynes and require the use of more toxic W (CO)5Or noble metals Au/Ag, Ru, etc., and the reaction time and temperature of most reactions are longer (Scheme 1).
1)1999,by lwasawa et al
2)2012，by Alabugin et al
3)2015,by Yamamoto et al
In summary, the problems of the prior art are as follows: the synthesis method in the prior art has the disadvantages of high raw material cost, long reaction time, high temperature, low reaction yield, poor functional group tolerance, complex post-treatment and environmental pollution.
The significance of solving the technical problems is as follows:
the invention provides a naphthofuran derivative and a synthesis method thereof, and develops a synthesis method of the naphthofuran derivative, which has the advantages of easily available raw materials, low cost and relatively mild reaction conditions.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a synthetic method of a naphthofuran derivative, the naphthofuran derivative and application.
The invention is realized in such a way that a method for synthesizing the naphthofuran derivatives is characterized in that a coupling reaction is carried out between a substrate and organic boric acid under a catalytic condition to form a allene intermediate, and 6 pi electrocyclic and 1, 3-hydrogen migration processes are carried out to obtain a target product.
The method specifically comprises the following steps: taking an o-furan aryl propargyl alcohol derivative and aryl boric acid as raw materials, and reacting the furan aryl propargyl alcohol protected by Boc with the aryl boric acid under the conditions of appropriate reaction temperature of transition metal, an additive and a solvent;
step two, obtaining the naphthofuran derivatives shown as the following formula (I);
further, the reaction formula of the synthetic method of the naphthofuran derivative is as follows:
wherein, R is1、R2Respectively selected from phenyl, naphthyl, aryl substituted by electron-donating groups, aryl substituted by electron-withdrawing groups, alkyl and hydrogen; r3Is halogen, methoxy and hydrogen.
Further, in the Boc protected o-furan aryl propargyl alcohol compound, a mother ring contains chlorine and fluorine of electron-withdrawing groups and methoxy of electron-donating groups; the aromatic ring in the arylboronic acid can be introduced with electron-withdrawing group chlorine, cyano, electron-donating group dimethyl, methoxy, neutral group naphthyl and hydrogen.
Further, the catalyst comprises Pd (dba)2、Pd(PPh3)4、CuI、FeCl3One or more of;
the additive comprises K2CO3、Cs2CO3、DBU、NEt3One or more of KOH and NaOH.
The reaction solvent comprises toluene, N-dimethylformamide, tetrahydrofuran, 1, 2-dichloroethane and 1, 4-dioxane.
The reaction molar ratio of the o-furan aryl propargyl alcohol derivative to the aryl boric acid to the catalyst to the additive is 1.0: (0.01-2.0): (0.5-2.0).
Further, the reaction temperature is 50-130 ℃.
The reaction temperature is 1-20 h.
The reaction is preferably carried out under nitrogen.
Another object of the present invention is to provide a naphthofuran derivative synthesized by the method for synthesizing a naphthofuran derivative, wherein the structure of the naphthofuran derivative is represented by formula (I):
wherein R is1、R2Respectively selected from phenyl, naphthyl, aryl substituted by electron-donating groups, aryl substituted by electron-withdrawing groups, alkyl and hydrogen; r3Is halogen, methoxy and hydrogen.
The invention also aims to provide a pore transfer material or photosensitizer prepared by utilizing the naphthopyran derivative.
The invention also aims to provide an application of the naphthofuran derivative in synthesizing antibacterial active medicaments.
The invention also aims to provide an application of the naphthofuran derivative in synthesizing an anti-tumor or anti-virus active medicament.
In summary, the advantages and positive effects of the invention are: the invention also provides application of the naphthofuran derivatives in preparation of antibacterial, antitumor and antiviral active medicines.
The preparation method has the advantages of cheap and easily obtained raw materials, high reaction yield, strong functional group tolerance, simple post-treatment, environmental friendliness and the like.
The invention designs an o-furan aryl propargyl alcohol substrate protected by Boc, and the substrate is reacted with organic boric acid to construct a naphthofuran derivative (Scheme 2) under the catalytic condition. The reaction process is as follows: the coupling reaction is carried out between the substrate and the organic boric acid under the catalysis condition to form a allene intermediate. Then 6 pi electrical cyclization and 1, 3-hydrogen migration processes are carried out to obtain a target product. The advantages are that: the method has the advantages of simple and easily obtained raw materials, wide reaction universality and good to excellent yield, and the acetylene bonds are converted into a allene intermediate with higher reaction activity in the reaction process, so the reaction conditions are relatively mild.
Drawings
FIG. 1 is a flow chart of a synthetic method of a naphthofuran derivative provided by an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The synthesis method in the prior art has high raw material cost, lower reaction yield, poor functional group tolerance, complicated post-treatment and environmental pollution.
In view of the problems in the prior art, the present invention provides a method for synthesizing naphthofuran derivatives, which is described in detail below with reference to the accompanying drawings.
The naphthofuran derivative provided by the invention is a main structural unit in a plurality of natural products and drug molecules, and most of the naphthofuran derivatives have stronger biological activity. The material has good potential application value in material chemistry, such as advanced hole transport materials, photosensitizers and the like.
The invention provides an unreported naphthofuran derivative, which has a structure shown in a formula (I):
wherein R is1、R2Respectively selected from phenyl, naphthyl, aryl substituted by electron-donating groups, aryl substituted by electron-withdrawing groups, alkyl and hydrogen; r3Is halogen, methoxy and hydrogen.
In the examples of the present invention, R1、R2Are respectively selected from phenyl, naphthyl, p-methylphenyl, p-methoxyphenyl, p-chlorophenyl, n-butyl, cyclopropyl and hydrogen; r3Is chlorine, fluorine, methoxyl or hydrogen.
As shown in fig. 1, an embodiment of the present invention further provides a method for synthesizing a naphthofuran derivative shown in formula (I), including:
and S101, reacting the furan aryl propargyl alcohol protected by the Boc with aryl boric acid under the conditions of transition metal, additive, solvent and proper reaction temperature.
S102, obtaining the naphthofuran derivative shown in the formula (I).
In step S10, the o-furan aryl propargyl alcohol derivative and the aryl boronic acid are used as starting materials.
The reaction process is shown as the formula (II):
wherein, R is1、R2Respectively selected from phenyl, naphthyl, aryl substituted by electron-donating groups, aryl substituted by electron-withdrawing groups, alkyl and hydrogen; r3Is halogen, methoxy and hydrogen.
In the present inventionIn the illustrated embodiment, R1、R2Are respectively selected from phenyl, naphthyl, p-methylphenyl, p-methoxyphenyl, p-chlorophenyl, n-butyl, cyclopropyl and hydrogen; r3Is chlorine, fluorine, methoxyl or hydrogen.
In the embodiment of the invention, in the Boc protected o-furan aryl propargyl alcohol compound, a mother ring contains chlorine and fluorine of electron-withdrawing groups and methoxy of electron-donating groups; the aromatic ring in the arylboronic acid can be introduced with electron-withdrawing group chlorine, cyano, electron-donating group dimethyl, methoxy, neutral group naphthyl, hydrogen and the like.
In an embodiment of the invention, the catalyst comprises Pd (dba)2、Pd(PPh3)4、CuI、FeCl3One or more of; preferably, Pd (PPh)3)4。
In the examples of the present invention, the additive comprises K2CO3、Cs2CO3、DBU、NEt3One or more of KOH and NaOH; preferably, it is Cs2CO3。
In the present embodiment, the reaction solvent includes toluene, N-dimethylformamide, tetrahydrofuran, 1, 2-dichloroethane, 1, 4-dioxane, etc.; preferably, it is 1, 4-dioxane.
In the embodiment of the invention, the reaction molar ratio of the o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst and the additive is 1.0: (0.01-2.0): (0.5-2.0); preferably, it is 1.0:1.0:0.02: 2.0.
In the embodiment of the invention, the reaction temperature is 50-130 ℃; preferably, it is 100 ℃.
In the embodiment of the invention, the reaction temperature is 1-20 h; preferably, it is 2-15 h.
In the examples of the present invention, the yields of the preparation methods were 72-80%.
In the present example, the reaction is preferably carried out under nitrogen.
The invention also provides the naphthofuran derivative prepared by the method.
In one embodiment, the synthesis of the naphthofuran derivatives is as follows:
wherein, R is1、R2Respectively selected from phenyl, naphthyl, aryl substituted by electron-donating groups, aryl substituted by electron-withdrawing groups, alkyl and hydrogen; r3Is halogen, methoxy and hydrogen.
Preferably, R1、R2Are respectively selected from phenyl, naphthyl, p-methylphenyl, p-methoxyphenyl, p-chlorophenyl, n-butyl, cyclopropyl and hydrogen; r3Is chlorine, fluorine, methoxyl or hydrogen.
The invention also provides application of the naphthofuran derivatives in preparation of antibacterial, antitumor and antiviral active medicines.
The invention is further described with reference to specific examples.
Example 1: synthesis of IA
The o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst, the additive and the reaction solvent are respectively o-furan phenyl propargyl alcohol, phenylboronic acid, palladium tetratriphenylphosphine, cesium carbonate and 1, 4-dioxane protected by Boc. The dosage of the compound is respectively 0.3mmol of O-furan phenyl propargyl alcohol protected by Boc, 0.6mmol of phenylboronic acid, 0.006mmol of tetratriphenylphosphine palladium, 0.6mmol of cesium carbonate and 3mL of 1, 4-dioxane. Reacting at 100 deg.C for 2 hr, cooling to room temperature, concentrating, and performing column chromatography to obtain the target product (IA) as pale yellow solid with isolation yield of 78%. Mp 194-196 ℃.
Nuclear magnetic data:1H NMR(CDCl3,400MHz):δ5.96(s,1H),5.60(d,J＝1.6Hz,1H),7.17(s,1H),7.25(d,J＝6.0Hz,4H),7.30(t,J＝6.0Hz,2H),7.36(t,J＝5.6Hz,4H),7.47(t,J＝5.6Hz,1H),7.59(t,J＝5.6Hz,1H),7.67(d,J＝1.6Hz,1H),7.80(d,J＝6.4Hz,1H),8.31(d,J＝6.4Hz,1H).13C NMR(CDCl3,100MHz):δ54.96,106.90,119.79,120.53,123.13,123.61,125.18,126.01,126.55,128.32,128.43,129.54,131.32,135.79,142.74,143.76,150.56.
high resolution mass spectral data: HRMS (ESI, m/z) calcd.for C25H19O[M+H]+calc.:335.1430；found:335.1429。
Example 2: synthesis of IB
The chlorine-substituted o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst, the additive and the reaction solvent are respectively o-furan phenyl propargyl alcohol, phenylboronic acid, palladium tetratriphenylphosphine, cesium carbonate and 1, 4-dioxane protected by Boc. The dosage of the catalyst is respectively 0.3mmol of Boc-protected chloro-substituted o-furan phenyl propargyl alcohol, 0.6mmol of phenylboronic acid, 0.006mmol of tetratriphenylphosphine palladium, 0.6mmol of cesium carbonate and 3mL of 1, 4-dioxane. Reacting at 100 deg.C for 2 hr, cooling to room temperature, concentrating, and performing column chromatography to obtain the target product formula (IB), a pale yellow solid, with an isolation yield of 72%. Mp 171-.
Nuclear magnetic data:1H NMR(CDCl3,400MHz):δ5.88(s,1H),6.53(s,1H),7.07(s,1H),7.17-7.34(m,11H),7.60-7.67(m,2H),8.23(s,1H).13C NMR(CDCl3,100MHz):δ54.75,107.11,119.23,121.25,123.00,124.73,126.13,126.88,128.73,129.72,130.16,132.14,136.46,142.77,144.64,149.90.
high resolution mass spectral data: HRMS (ESI, m/z) calcd.for C25H18ClO[M+H]+calc.:369.1041；found:369.1045。
Example 3: synthesis of IC
The methoxyl substituted o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst, the additive and the reaction solvent are respectively methoxyl substituted o-furan phenyl propargyl alcohol, phenylboronic acid, palladium tetratriphenylphosphine, cesium carbonate and 1, 4-dioxane which are protected by Boc. The dosage of the catalyst is respectively 0.3mmol of Boc-protected chloro-substituted o-furan phenyl propargyl alcohol, 0.6mmol of phenylboronic acid, 0.006mmol of tetratriphenylphosphine palladium, 0.6mmol of cesium carbonate and 3mL of 1, 4-dioxane. Reacting at 100 deg.C for 3 hr, cooling to room temperature, concentrating, and performing column chromatography to obtain the target product of formula (IC) as pale yellow solid with isolation yield of 79%. Mp 135-.
Nuclear magnetic data:1H NMR(CDCl3,400MHz):δ3.84(s,3H),5.89(s,1H),6.50(s,1H),7.02(s,1H),7.09(s,1H),7.18-7.32(m,11H),7.55(s,1H),8.16(d,J＝8.8Hz,1H).13C NMR(CDCl3,100MHz):δ54.82,55.15,106.88,107.27,115.82,118.32,121.60,122.07,122.47,126.74,128.66,129.79,132.92,136.68,143.10,143.39,151.22,157.68.
high resolution mass spectral data: HRMS (ESI, m/z) calcd.for C26H21O2[M+H]+calc.:365.1536；found:365.1536。
Example 4: synthesis of ID
The o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst, the additive and the reaction solvent are respectively o-furan phenyl butyl propargyl alcohol, phenylboronic acid, palladium tetratriphenylphosphine, cesium carbonate and 1, 4-dioxane protected by Boc. The dosage of the compound is respectively 0.3mmol of O-furan phenyl butyl propargyl alcohol protected by Boc, 0.6mmol of phenylboronic acid, 0.006mmol of tetratriphenylphosphine palladium, 0.6mmol of cesium carbonate and 3mL of 1, 4-dioxane. Reacting at 100 deg.C for 2 hr, cooling to room temperature, concentrating, and performing column chromatography to obtain the target product (ID) as brown oily liquid with isolation yield of 70%.
Nuclear magnetic data:1H NMR(CDCl3,400MHz):δ0.87(bs,3H),1.35(bs,4H),2.17-2.27(m,2H),4.30(bs,1H),6.79(s,1H),7.16-7.29(m,5H),7.46-7.64(m,4H),7.91(d,J＝7.2Hz,1H),8.25(d,J＝6.8Hz,1H).13C NMR(CDCl3,100MHz):δ 13.75,22.54,30.05,34.62,48.79,106.62,120.03,120.44,120.58,123.57,125.37,125.93,126.37,128.32,128.37,128.58,131.78,136.93,143.99,144.82,150.88.
high resolution mass spectral data: HRMS (ESI, m/z) calcd.for C23H23O[M+H]+calc.:315.1743；found:315.1372.
Example 5: synthesis of IE
The o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst, the additive and the reaction solvent are respectively o-furan phenyl p-chlorophenyl propargyl alcohol, phenylboronic acid, palladium tetratriphenylphosphine, cesium carbonate and 1, 4-dioxane protected by Boc. The dosage of the compound is respectively 0.3mmol of O-furan phenyl butyl propargyl alcohol protected by Boc, 0.6mmol of phenylboronic acid, 0.006mmol of tetratriphenylphosphine palladium, 0.6mmol of cesium carbonate and 3mL of 1, 4-dioxane. Reacting at 100 deg.C for 2 hr, cooling to room temperature, concentrating, and performing column chromatography to obtain the target product of formula (IE), which is pale yellow solid with isolation yield of 80%. mp 109-.
Nuclear magnetic data:1H NMR(CDCl3,400MHz):δ5.87(s,1H),6.52(s,1H),7.07-7.17(m,5H),7.23-7.33(m,5H),7.43(d,J＝7.6Hz,1H),7.52(t,J＝7.6Hz,1H),7.63(s,1H),7.75(d,J＝8.0Hz,1H),8.27(d,J＝8.4Hz,1H).13C NMR(CDCl3,100MHz):δ54.12,106.89,120.00,120.76,123.31,123.60,125.53,126.41,127.00,128.55,128.80,128.83,129.67,131.09,131.50,132.62,135.46,141.58,142.50,144.19,150.92.
high resolution mass spectral data: HRMS (ESI, m/z) calcd.for C25H18ClO[M+H]+calc.:369.1041；found:369.1078。
Example 6: synthesis of IF
The o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst, the additive and the reaction solvent are respectively o-furan phenyl p-methoxyphenyl propargyl alcohol protected by Boc, phenylboronic acid, palladium tetratriphenylphosphine, cesium carbonate and 1, 4-dioxane. The dosage of the compound is respectively 0.3mmol of O-furan phenyl butyl propargyl alcohol protected by Boc, 0.6mmol of phenylboronic acid, 0.006mmol of tetratriphenylphosphine palladium, 0.6mmol of cesium carbonate and 3mL of 1, 4-dioxane. Reacting at 100 deg.C for 2 hr, cooling to room temperature, concentrating, and performing column chromatography to obtain the desired product of formula (IF), white solid, and isolation yield 78%. mp 107-.
Nuclear magnetic data:1H NMR(CDCl3,400MHz):δ3.77(s,3H),5.85(s,1H),6.54(s,1H),6.83(d,J＝8.0Hz,2H),7.09(d,J＝7.6Hz,3H),7.17-7.29(m,5H),7.41(t,J＝7.2Hz,1H),7.52(t,J＝7.2Hz,1H),7.61(s,1H),7.74(d,J＝7.6Hz,1H),8.26(d,J＝8.0Hz,1H).13C NMR(CDCl3,100MHz):δ53.97,55.06,107.06,113.93,119.96,120.68,123.18,123.79,125.38,126.19,126.69,128.53,128.64,129.69,130.70,131.56,135.12,136.40,143.38,144.04,150.86,158.52.
high resolution mass spectral data: HRMS (ESI, m/z) calcd.for C26H21O2[M+H]+calc.:365.1536；found:365.1537。
Example 7: synthesis of IG
The o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst, the additive and the reaction solvent are respectively o-furan phenyl propargyl alcohol, p-cyanobenzene boric acid, tetratriphenylphosphine palladium, cesium carbonate and 1, 4-dioxane protected by Boc. The dosage of the compound is respectively 0.3mmol of O-furan phenyl butyl propargyl alcohol protected by Boc, 0.6mmol of phenylboronic acid, 0.006mmol of tetratriphenylphosphine palladium, 0.6mmol of cesium carbonate and 3mL of 1, 4-dioxane. Reacting at 100 deg.C for 2 hr, cooling to room temperature, concentrating, and performing column chromatography to obtain the target product of formula (IF), and light yellow solid with isolation yield of 70%. mp 137-.
Nuclear magnetic data:1H NMR(CDCl3,400MHz):δ5.97(s,1H),6.53(d,J＝1.2Hz,1H),7.08(s,1H),7.18(d,J＝7.6Hz,2H),7.26-7.38(m,5H),7.47(t,J＝7.6Hz,1H),7.57-7.63(m,3H),7.67(d,J＝0.8Hz,1H),7.78(d,J＝8.4Hz,1H),8.30(d,J＝7.6Hz,1H).13C NMR(CDCl3,100MHz):δ54.71,106.64,110.65,119.03,120.02,120.82,123.39,123.43,125.67,126.62,127.33,128.51,128.97,129.64,130.49,131.41,132.51,134.44,141.49,144.34,148.64,150.98.
high resolution mass spectral data: HRMS (ESI, m/z) calcd.for C26H18NO[M+H]+calc.:360.1383；found:360.1384。
Example 8: synthesis of IH
The o-furan aryl propargyl alcohol derivative, the aryl boric acid, the catalyst, the additive and the reaction solvent are respectively o-furan phenyl p-methoxyphenyl propargyl alcohol protected by Boc, phenylboronic acid, palladium tetratriphenylphosphine, cesium carbonate and 1, 4-dioxane. The dosage of the compound is respectively 0.3mmol of O-furan phenyl butyl propargyl alcohol protected by Boc, 0.6mmol of phenylboronic acid, 0.006mmol of tetratriphenylphosphine palladium, 0.6mmol of cesium carbonate and 3mL of 1, 4-dioxane. Reacting at 100 deg.C for 9 hr, cooling to room temperature, concentrating, and performing column chromatography to obtain the desired product of formula (IF), white solid, with isolation yield of 72%. mp 107-.
Nuclear magnetic data:1H NMR(CDCl3,400MHz):δ2.05(s,6H),6.29(s,1H),6.35(s,1H),7.05(d,J＝7.2Hz,2H),7.14(t,J＝8.4Hz,4H),7.21-7.31(m,3H),7.40(t,J＝7.6Hz,1H),7.53(t,J＝7.6Hz,1H),7.61(d,J＝1.2Hz,1H),7.72(d,J＝8.0Hz,1H),8.28(d,J＝8.0Hz,1H).13C NMR(CDCl3,100MHz):δ21.66,50.10,107.02,119.97,120.61,122.78,124.04,125.32,126.12,126.45,127.09,128.49,128.53,129.70,129.96,131.71,134.85,138.05,139.54,141.42,144.04,150.69.
high resolution mass spectral data: HRMS (ESI, m/z) calcd.for C27H23O[M+H]+calc.:363.1735；found:363.1643。
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (10)
1. A method for synthesizing a naphthofuran derivative, comprising:
the coupling reaction is carried out on the substrate and organic boric acid under the catalysis condition to form a allene intermediate, and 6 pi electrocyclization and 1, 3-hydrogen migration processes are carried out to obtain a target product.
2. The method of synthesizing a naphthofuran derivative of claim 1, further comprising:
step one, reacting furan aryl propargyl alcohol protected by Boc with aryl boric acid under the conditions of transition metal, additive, solvent and proper reaction temperature;
step two, obtaining the naphthofuran derivatives shown as the following formula (I);
3. the method for synthesizing a naphthofuran derivative according to claim 2, wherein the reaction formula of the method for synthesizing a naphthofuran derivative is:
wherein, R is1、R2Respectively selected from phenyl, naphthyl, aryl substituted by electron-donating groups, aryl substituted by electron-withdrawing groups, alkyl and hydrogen; r3Is halogen, methoxy and hydrogen.
4. The method for synthesizing a naphthofuran derivative as claimed in claim 2, wherein said Boc-protected o-furylarylpropargyl alcohol compound has a mother ring containing chlorine and fluorine as electron-withdrawing groups and a methoxy as electron-donating group; the aromatic ring in the arylboronic acid can be introduced with electron-withdrawing group chlorine, cyano, electron-donating group dimethyl, methoxy, neutral group naphthyl and hydrogen.
5. The method of claim 2, wherein the catalyst comprises Pd (dba)2、Pd(PPh3)4、CuI、FeCl3One or more of;
the additive comprises K2CO3、Cs2CO3、DBU、NEt3One or more of KOH and NaOH;
the reaction solvent comprises toluene, N-dimethylformamide, tetrahydrofuran, 1, 2-dichloroethane and 1, 4-dioxane;
the reaction molar ratio of the o-furan aryl propargyl alcohol derivative to the aryl boric acid to the catalyst to the additive is 1.0: (0.01-2.0): (0.5-2.0).
6. The method for synthesizing a naphthofuran derivative of claim 2, wherein the reaction temperature is 50 to 130 ℃;
the reaction temperature is 1-20 h;
the reaction is preferably carried out under nitrogen.
7. A naphthofuran derivative synthesized by the method for synthesizing a naphthofuran derivative according to claim 1, wherein the structure of the naphthofuran derivative is represented by the formula (I):
wherein R is1、R2Respectively selected from phenyl, naphthyl, aryl substituted by electron-donating groups, aryl substituted by electron-withdrawing groups, alkyl and hydrogen; r3Is halogen, methoxy and hydrogen.
8. A pore transport material or photosensitizer prepared using the naphthofuran-based derivative of claim 7.
9. Use of a naphthofuran derivative as claimed in claim 7 in the synthesis of a medicament with antibacterial activity.
10. Use of a naphthofuran derivative as claimed in claim 7 in the synthesis of a medicament with anti-tumour or anti-viral activity.
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