JPS6328074B2 - - Google Patents
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- Publication number
- JPS6328074B2 JPS6328074B2 JP15231281A JP15231281A JPS6328074B2 JP S6328074 B2 JPS6328074 B2 JP S6328074B2 JP 15231281 A JP15231281 A JP 15231281A JP 15231281 A JP15231281 A JP 15231281A JP S6328074 B2 JPS6328074 B2 JP S6328074B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- represented
- acetyl group
- hours
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000001875 compounds Chemical class 0.000 claims description 44
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 13
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 5
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000002841 Lewis acid Substances 0.000 claims description 4
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 claims description 4
- 150000007517 lewis acids Chemical class 0.000 claims description 4
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 3
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 1
- 238000006640 acetylation reaction Methods 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 238000006400 oxidative hydrolysis reaction Methods 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
- -1 aliphatic alcohols Chemical group 0.000 description 20
- 239000000203 mixture Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000243 solution Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 230000035484 reaction time Effects 0.000 description 8
- DUXJAHFLYZUOPT-NFSXTHTRSA-N [(2r,3r,4r,5r,6s)-3,4,6-triacetyloxy-5-(1,3-dioxoisoindol-2-yl)oxan-2-yl]methyl acetate Chemical compound CC(=O)O[C@H]1[C@@H](OC(C)=O)[C@@H](COC(=O)C)O[C@@H](OC(C)=O)[C@@H]1N1C(=O)C2=CC=CC=C2C1=O DUXJAHFLYZUOPT-NFSXTHTRSA-N 0.000 description 7
- 230000000704 physical effect Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- MSWZFWKMSRAUBD-UHFFFAOYSA-N 2-Amino-2-Deoxy-Hexose Chemical compound NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 5
- VLQCJDWKOKACBQ-CMKHUCCNSA-N C(C)(=O)N[C@H]1[C@@H](O[C@@H]([C@@H]([C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)O)CO)OC[C@@H](COCCCCCCCCCCCCCC)OCCCCCCCCCCCCCC Chemical compound C(C)(=O)N[C@H]1[C@@H](O[C@@H]([C@@H]([C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)O)CO)OC[C@@H](COCCCCCCCCCCCCCC)OCCCCCCCCCCCCCC VLQCJDWKOKACBQ-CMKHUCCNSA-N 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229930186217 Glycolipid Natural products 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- VELGMVLNORPMAO-JTFNWEOFSA-N n-[(e)-1-[(3r,4r,5s,6r)-5-[(2s,3r,4r,5r,6r)-5-[(2s,3r,4r,5r,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)-4-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,4-dihydroxy-6-(hydroxym Chemical compound O[C@@H]1[C@@H](O)C(OCC(NC(=O)CCCCCCCCCCCCCCCCC)C(O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 VELGMVLNORPMAO-JTFNWEOFSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 229940100892 mercury compound Drugs 0.000 description 2
- 150000002731 mercury compounds Chemical class 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- KOFZTCSTGIWCQG-UHFFFAOYSA-N 1-bromotetradecane Chemical compound CCCCCCCCCCCCCCBr KOFZTCSTGIWCQG-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- IAJHLVPJJCPWLF-UHFFFAOYSA-N 2,3-di(tetradecoxy)propan-1-ol Chemical compound CCCCCCCCCCCCCCOCC(CO)OCCCCCCCCCCCCCC IAJHLVPJJCPWLF-UHFFFAOYSA-N 0.000 description 1
- GZUFURWAWJHNPE-UHFFFAOYSA-N 2,3-di(tetradecoxy)propoxymethylbenzene Chemical compound CCCCCCCCCCCCCCOCC(OCCCCCCCCCCCCCC)COCC1=CC=CC=C1 GZUFURWAWJHNPE-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229910017852 NH2NH2 Inorganic materials 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- BLAKAEFIFWAFGH-UHFFFAOYSA-N acetyl acetate;pyridine Chemical compound C1=CC=NC=C1.CC(=O)OC(C)=O BLAKAEFIFWAFGH-UHFFFAOYSA-N 0.000 description 1
- 239000012345 acetylating agent Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- RBADLHJXVXRWQY-UHFFFAOYSA-N benzene;nitromethane Chemical compound C[N+]([O-])=O.C1=CC=CC=C1 RBADLHJXVXRWQY-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 150000002016 disaccharides Chemical group 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000000194 fatty acid Chemical group 0.000 description 1
- 229930195729 fatty acid Chemical group 0.000 description 1
- 150000004665 fatty acids Chemical group 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 150000004043 trisaccharides Chemical group 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は、下記の一般式で表わされる新規なグ
リセロ糖脂質化合物及びその製造法に関するもの
である。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel glyceroglycolipid compound represented by the following general formula and a method for producing the same.
(ただし、式中、R2は、水素又はアセチル基を
示し、Acはアセチル基を示す。)
糖脂質(glycolipid)は、有機溶媒に溶ける脂
質としての性質から、多糖生化学のうちでも特異
な位置を占めている。これを脂質の世界からみれ
ば、リン脂質(phospholipid)とともに、複合脂
質の一大分野を形成し、脂質と糖質の世界を結ぶ
かけ橋ともなつている。糖脂質は、化学的構成の
面からは、「脂肪族アルコール又は脂肪酸と結合
した糖質からなる複合脂質」として総括すること
ができる。そこで、この領域を構成する代表的な
脂質群とその主な分布を挙げれば次の如くであ
る。すなわち、スフインゴ糖脂質(動物)、フイ
トグリコリピド(植物)、グリセロ糖脂質(動物、
植物、微生物)及び構成単位としてスフインゴジ
ン、グリセリンを有さないその他の糖脂質(微生
物)などがある。 (However, in the formula, R 2 represents hydrogen or an acetyl group, and Ac represents an acetyl group.) Glycolipids are unique among polysaccharide biochemists due to their properties as lipids that dissolve in organic solvents. occupying a position. From the perspective of the world of lipids, along with phospholipids, they form a major field of complex lipids, and serve as a bridge between the worlds of lipids and carbohydrates. From the viewpoint of chemical composition, glycolipids can be summarized as "complex lipids consisting of carbohydrates bonded to aliphatic alcohols or fatty acids." Therefore, the typical lipid groups constituting this region and their main distribution are as follows. Namely, sphingoglycolipids (animals), phytoglycolipids (plants), glyceroglycolipids (animals,
plants, microorganisms) and other glycolipids (microorganisms) that do not have sphingogine or glycerin as a constituent unit.
スフインゴ糖脂質の1つに、アシアロGM1
(asialo GM1)(A)がある。該物質は、動物の極
めて初期の胸腺細胞上に存在し、免疫機能との密
接な関連性について、報告がなされている(S.
Habu et al、J.Immunology、125.2284〜2288
(1980))。 Asialo GM1 is one of the sphingoglycolipids.
(asialo GM1) There is (A). This substance is present on the very early thymocytes of animals, and it has been reported that it is closely related to immune function (S.
Habu et al, J. Immunology, 125 . 2284~2288
(1980)).
上記アシアロGM1の化学的構成と免疫機能と
の関連は、末端の二ないし三糖類部分
(terminaldi−又はtrisaccharide sequence)に
あると考えられる。そこで、本発明者らは、
GM1の末端二糖類部分のモデルとなるグリセロ
糖脂質化合物の合成について鋭意研究を行つた結
果、新規なグリセロ糖脂質を合成することに成功
し、本発明を完成するに至つた。 The relationship between the chemical structure of asialo GM1 and immune function is thought to be in the terminal di- or trisaccharide sequence. Therefore, the present inventors
As a result of intensive research into the synthesis of a glyceroglycolipid compound that serves as a model for the terminal disaccharide moiety of GM1, we succeeded in synthesizing a novel glyceroglycolipid and completed the present invention.
本発明の目的化合物は、免疫機能などの生化学
的機能を解明するための生化学的試薬としての利
用が期待される他、該化合物を抗原として用い、
特異的抗体を生産したり、それ自身、体謝括抗剤
としての利用が期待される。 The target compound of the present invention is expected to be used as a biochemical reagent for elucidating biochemical functions such as immune function, and also by using the compound as an antigen.
It is expected to produce specific antibodies and be used as a metabolic inhibitor.
以下に、本発明を説明する。 The present invention will be explained below.
D−グルコサミン塩酸塩(1)を、まず、アルカリ
金属アルコキシド−アルコールで中和する。中和
剤としては、NaOCH3−CH3OH、KOCH3−
CH3OH、NaOC2H5−C2H5OH、KOC2H5−
C2H5OHが適当である。 D-glucosamine hydrochloride (1) is first neutralized with an alkali metal alkoxide-alcohol. As a neutralizing agent, NaOCH 3 −CH 3 OH, KOCH 3 −
CH3OH , NaOC2H5 − C2H5OH , KOC2H5−
C2H5OH is suitable.
次いで、得られた混合物をフタロイル化する。 The resulting mixture is then phthaloylated.
この反応は、無水フタル酸をトリエチルアミン
等の有機塩基の存在下で撹拌して行う。反応温度
は、室温〜60℃、反応時間は、約1〜50時間が適
当である。 This reaction is carried out by stirring phthalic anhydride in the presence of an organic base such as triethylamine. The reaction temperature is room temperature to 60°C, and the reaction time is suitably about 1 to 50 hours.
次に、得られた化合物をアセチル化すると、フ
タルイミド体(2)を得る。アセチル化剤としては、
無水酢酸−ピリジン、無水酢酸−コリジンが適当
である。反応温度、反応時間は、それぞれ、室温
〜60℃、約50分〜2時間が適当である。 Next, the obtained compound is acetylated to obtain the phthalimide compound (2). As an acetylating agent,
Acetic anhydride-pyridine and acetic anhydride-collidine are suitable. The appropriate reaction temperature and reaction time are room temperature to 60°C and approximately 50 minutes to 2 hours, respectively.
次に、得られたフタルイミド体(2)を、ルイス酸
の存在下、1,2−ジ−O−テトラデシルグリセ
ロール(3)と撹拌反応せしめて、β−グリコシド体
(4)を得る。ルイス酸としては、
(CH3)3SiOSO2CF3、ZnCl2、SnCl4等が用いられ
る。溶媒としては、ジクロルエタン、ジクロルメ
タン、四塩化炭素等が適当である。反応温度は室
温で充分であり、反応時間は、約2〜10時間が適
当である。 Next, the obtained phthalimide (2) was stirred and reacted with 1,2-di-O-tetradecylglycerol (3) in the presence of a Lewis acid to form a β-glycoside.
(4) is obtained. As a Lewis acid,
( CH3 ) 3SiOSO2CF3 , ZnCl2 , SnCl4, etc. are used. Suitable solvents include dichloroethane, dichloromethane, carbon tetrachloride, and the like. Room temperature is sufficient for the reaction temperature, and a suitable reaction time is about 2 to 10 hours.
なお、グリセロール(3)は、公知の方法、例え
ば、D−マンニトールをアセトン−ZnCl2により
イソプロピリデン化した後、過ヨウ素酸塩と反応
させて、1,2−O−イソプロピリデングリコー
ルとなし、該化合物を、常法にてベンジル化した
後、テトラデシルブロミドと反応させて1−O−
ベンジル−2,3−ジ−O−テトラデシルグリセ
ロールとなし、該化合物を、常法により、例え
ば、pd−C触媒存在下に水素接触還元すること
によつて得られる(J.Org.Chem.、31.498
(1966);Biochemistry、2、No.2、Mar.〜
Apr.394(1963)参照)。 Glycerol (3) can be obtained by a known method, for example, by isopropylidening D-mannitol with acetone-ZnCl 2 and then reacting it with periodate to form 1,2-O-isopropylidene glycol. The compound was benzylated in a conventional manner and then reacted with tetradecyl bromide to form 1-O-
benzyl-2,3-di-O-tetradecylglycerol, which can be obtained by conventional methods such as hydrogen catalytic reduction in the presence of a pd-C catalyst (J.Org.Chem. ,31.498
(1966); Biochemistry, 2, No. 2, Mar.~
See Apr. 394 (1963)).
次に、得られたβ−グリコシド体(4)を脱フタロ
イル化して、アミン体(5)を得る。この反応は、溶
媒中、アミン類と共に還流撹拌を行うことにより
進行する。アミン類としては、n−C4H9NH2、
n−C5H11NH2、NH2NH2等が適当であり、溶
媒としては、メタノール、エタノール、エーテ
ル、テトラヒドロフラン等が適当である。反応温
度、反応時間は、それぞれ、約50〜150℃、約15
〜24時間が適当である。 Next, the obtained β-glycoside (4) is dephthaloylated to obtain an amine (5). This reaction proceeds by stirring under reflux with the amine in a solvent. As amines, n-C 4 H 9 NH 2 ,
n- C5H11NH2 , NH2NH2 , etc. are suitable, and as a solvent , methanol, ethanol, ether, tetrahydrofuran, etc. are suitable. The reaction temperature and reaction time are approximately 50 to 150℃ and approximately 15℃, respectively.
~24 hours is appropriate.
得られたアミン体(5)をN−アセチル化して、N
−アセチル体(6)を得る。この反応は、溶媒中、無
水酢酸を加えて撹拌することにより進行する。溶
媒としては、メタノール、エタノール、エーテ
ル、テトラヒドロフラン等、あるいは、これらの
混合溶媒を用いてもよい。反応温度、反応時間
は、それぞれ、約0〜10℃、約1〜10時間が適当
である。 The obtained amine compound (5) was N-acetylated to give N
- Obtain acetyl compound (6). This reaction proceeds by adding and stirring acetic anhydride in a solvent. As the solvent, methanol, ethanol, ether, tetrahydrofuran, etc., or a mixed solvent thereof may be used. Appropriate reaction temperature and reaction time are approximately 0 to 10°C and approximately 1 to 10 hours, respectively.
次に、得られたN−アセチル体(6)をベンジリデ
ン化して、ベンジリデン体(7)を得る。この反応
は、ルイス酸触媒存在下、ベンズアルデヒドと共
に撹拌することにより進行する。触媒としては、
ZnCl2、SnCl4、FeCl3等が用いられ、無溶媒又は
イソプロピルエーテル中で反応させるのが適当で
ある。 Next, the obtained N-acetyl compound (6) is benzylidened to obtain a benzylidene compound (7). This reaction proceeds by stirring together with benzaldehyde in the presence of a Lewis acid catalyst. As a catalyst,
ZnCl 2 , SnCl 4 , FeCl 3 and the like are used, and it is appropriate to react without a solvent or in isopropyl ether.
次に得られたベンジリデン体(7)をグリコシル化
して、ベンジリデンジサツカライド(9)を得る。こ
の反応は、水銀化合物存在下、アセトハロゲノー
ス(8)を加えて撹拌すればよい。水銀化合物として
は、Hg(CN)2、HgBr2が用いられる。溶媒とし
ては、ベンゼン、トルエン、キシレン等の芳香族
アプロテイツク溶媒とニトロエタン、ニトロメタ
ン等の混合溶媒が適当である。反応温度、反応時
間は、それぞれ、約50〜80℃、約15〜24時間が適
当である。 Next, the obtained benzylidene derivative (7) is glycosylated to obtain benzylidene disaccharide (9). This reaction can be carried out by adding acetohalogenose (8) and stirring in the presence of a mercury compound. As the mercury compound, Hg(CN) 2 and HgBr 2 are used. Suitable solvents include mixed solvents of aromatic aprotic solvents such as benzene, toluene and xylene, and nitroethane and nitromethane. Appropriate reaction temperature and reaction time are approximately 50 to 80°C and approximately 15 to 24 hours, respectively.
次に、得られたベンジリデンジサツカライド(9)
のベンジリデン部分を脱ベンジリデン化して、ジ
サツカライド(10)を得る。この加水分解反応は、酢
酸、希塩酸等の酸性溶液中で撹拌することにより
進行する。反応温度、反応時間は、それぞれ、室
温〜70℃、約2〜25時間が適当である。 Next, the obtained benzylidene disaccharide (9)
The benzylidene moiety of is debenzylidened to give disactucharide (10). This hydrolysis reaction proceeds by stirring in an acidic solution such as acetic acid or dilute hydrochloric acid. The appropriate reaction temperature and reaction time are room temperature to 70°C and approximately 2 to 25 hours, respectively.
次に、得られたジサツカライド(10)を、脱アセチ
ル化して、目的化合物(11)を得る。この反応は、塩
基の存在下、で還流撹拌して行う。塩基として
は、(C2H5)3N、(C6H5)3N等の有機塩基、
NaOCH3、NaOC2H5、KOCH3、KOC2H5等の
アルカリ金属アルコキシドを用いてもよい。溶媒
としては、メタノール−水、エタノール−水等の
含水アルコールが適当である。反応温度及び反応
時間は、それぞれ、約0〜100℃、約1〜20時間
が適当である。 Next, the obtained disactucharide (10) is deacetylated to obtain the target compound (11). The reaction is carried out in the presence of a base with stirring at reflux. Examples of the base include organic bases such as (C 2 H 5 ) 3 N and (C 6 H 5 ) 3 N;
Alkali metal alkoxides such as NaOCH 3 , NaOC 2 H 5 , KOCH 3 and KOC 2 H 5 may also be used. As the solvent, hydrous alcohols such as methanol-water and ethanol-water are suitable. Appropriate reaction temperature and reaction time are approximately 0 to 100°C and approximately 1 to 20 hours, respectively.
次に、本発明の化合物(11)の製造例を、図に示
す。 Next, a production example of the compound (11) of the present invention is shown in the figure.
以下に、本発明の実施例を示す。なお、化合物
(2)、(4)、(5)、(6)、(7)、(9)、(10)および(11)は、い
ずれ
も新規化合物である。 Examples of the present invention are shown below. In addition, the compound
(2), (4), (5), (6), (7), (9), (10) and (11) are all new compounds.
実施例の物理的性質において、特に記載のない
ものは次の測定条件によるものである。 In the physical properties of Examples, unless otherwise specified, the following measurement conditions were used.
比旋光度は、CHCl3中、25℃で測定した。 1H
−N.M.R.は、テトラメチルシランを内部標準と
して用い、周波数100MHzで測定した。 Specific optical rotations were measured at 25°C in CHCl3 . 1H
-NMR was measured at a frequency of 100 MHz using tetramethylsilane as an internal standard.
13C−N.M.R.は、DMSO−d6を内部標準とし
て用い、周波数25.05MHzで測定した。 13 C-NMR was measured at a frequency of 25.05 MHz using DMSO-d 6 as an internal standard.
Rf値は、シリカゲル60F254(西ドイツメルク社
製)、を用いて、厚さ0.25mmのコーテイングを行
つた薄層クロマトグラフイーで測定した。 The Rf value was measured by thin layer chromatography using silica gel 60F 254 (manufactured by Merck & Co., West Germany) coated with a thickness of 0.25 mm.
実施例 1
1,3,4,6−テトラ−O−アセチル−2−
デオキシ−2−フタリミド−β−D−ガラクト
ピラノース(2)
Na(2.1g、0.09モル)及びメタノール(90ml)
より調製したNaOCH3のメタノール溶液に、15
〜20℃で撹拌しながら、すぐにD−グルコサミン
塩酸塩(1)(19.8g、0.09モル)を加えた。得られ
た混合物を、更に5分間撹拌し、過した。この
過液に、粉末状無水フタル酸(6.6g、0.446モ
ル)とトリエチルアミン(9g)を加えた。得ら
れた混合物を、清澄溶液になるまで、15〜20℃で
撹拌し、更に、無水フタル酸(7.2g、0.486モ
ル)を加えた。得られた混合物を、15〜20℃で30
分間、さらに50℃で20分間撹拌した。得られた混
合物を、室温まで冷却後、エーテル(300ml)を
加えると結晶が得られ、これを集めて乾燥してピ
リジン(200ml)と無水酢酸(100ml)の溶液に溶
解した。得られた混合物を15〜20℃で15時間撹拌
し、減圧下溶媒留去し、得られた油状残渣を、
SiO2−ハイフロス−パーセル(2:1500g)を
用いて、クロマトグラフイーに付すと(溶媒:ト
ルエン−酢酸エチル=3:1)、化合物(2)が19.4
g得られた(収率:44.3%)。Example 1 1,3,4,6-tetra-O-acetyl-2-
Deoxy-2-phthalimido-β-D-galactopyranose (2) Na (2.1 g, 0.09 mol) and methanol (90 ml)
To a methanol solution of NaOCH 3 prepared from 15
D-glucosamine hydrochloride (1) (19.8 g, 0.09 mol) was immediately added while stirring at ~20°C. The resulting mixture was stirred for an additional 5 minutes and filtered. Powdered phthalic anhydride (6.6 g, 0.446 mol) and triethylamine (9 g) were added to the filtrate. The resulting mixture was stirred at 15-20° C. until a clear solution was obtained and additional phthalic anhydride (7.2 g, 0.486 mol) was added. The resulting mixture was heated at 15-20 °C for 30
The mixture was further stirred at 50° C. for 20 minutes. After cooling the resulting mixture to room temperature, ether (300 ml) was added to obtain crystals, which were collected, dried, and dissolved in a solution of pyridine (200 ml) and acetic anhydride (100 ml). The resulting mixture was stirred at 15-20°C for 15 hours, the solvent was distilled off under reduced pressure, and the resulting oily residue was
When subjected to chromatography using SiO 2 -Hyfloss-Purcel (2:1500g) (solvent: toluene-ethyl acetate = 3:1), compound (2) was obtained at 19.4
g (yield: 44.3%).
〔化合物(2)の物理的性質〕
m.p.:99〜101℃(イソプロピルエーテルより再
結晶)
比旋光度:〔α〕D+31.1゜(C=0.83)
Rf値:0.45(トルエン−酢酸エチル=2:1)
1H−NMRδH:7.9〜7.7(4H、m、フタロイル
基)、6.45(1H、d、J=8Hz、H−1)、5.94
(1H、q、J=2.5、10Hz、H−3)、5.51(1H、
d、J=2.5Hz、H−4)、4.66(1H、q、J=
8、10Hz、H−2)、4.21(3H、bs、H−6、
H−6′、H−5)、2.21、2.06、2.01及び1.86(4
個の3H、s、OAc×4)
元素分析:(C22H23O11Nとして)
C H N
計算値(%) 55.35 4.86 2.93
実測値(%) 55.84 4.93 2.85
実施例 2
3−O−(3,4,6−トリ−O−アセチル−
2−デオキシ−2−フタリミド−β−D−ガラ
クトピラノシル)−1,2−ジ−O−テトラデ
ジル−sn−グリセロール(4)
化合物(2)(3.7g、7.75ミリモル)と化合物(3)
(5.6g、11.6ミリモル)のジクロルエタン溶液
(30ml)に、(CH3)3SiOSO2CF3(1.7ml)を加え、
15〜20℃で3時間撹拌し、得られた混合物を氷水
に注ぎ、CHCl3で抽出した。有機層をNaHCO3
溶液、水で洗浄し、MgSO4で乾燥し、次いで減
圧下溶媒留去した。[Physical properties of compound (2)] mp: 99-101°C (recrystallized from isopropyl ether) Specific rotation: [α] D +31.1° (C = 0.83) Rf value: 0.45 (toluene-ethyl acetate = 2:1) 1H -NMRδH: 7.9-7.7 (4H, m, phthaloyl group), 6.45 (1H, d, J = 8Hz, H-1), 5.94
(1H, q, J=2.5, 10Hz, H-3), 5.51 (1H,
d, J=2.5Hz, H-4), 4.66 (1H, q, J=
8, 10Hz, H-2), 4.21 (3H, bs, H-6,
H-6', H-5), 2.21, 2.06, 2.01 and 1.86 (4
3H, s, OAc×4) Elemental analysis: (as C 22 H 23 O 11 N) C H N Calculated value (%) 55.35 4.86 2.93 Actual value (%) 55.84 4.93 2.85 Example 2 3-O-( 3,4,6-tri-O-acetyl-
2-Deoxy-2-phthalimido-β-D-galactopyranosyl)-1,2-di-O-tetradedyl-sn-glycerol (4) Compound (2) (3.7 g, 7.75 mmol) and Compound (3)
(5.6 g, 11.6 mmol) in dichloroethane (30 ml) was added (CH 3 ) 3 SiOSO 2 CF 3 (1.7 ml),
Stirred at 15-20 °C for 3 hours, the resulting mixture was poured into ice water and extracted with CHCl3 . NaHCO3 the organic layer
The solution was washed with water, dried over MgSO 4 and then evaporated under reduced pressure.
残渣を、SiO2−ハイフロスーパーセル(2:
1、500g)を用いて、クロマトグラフイーに付
すと(溶媒:トルエン−酢酸エチル=7:1)、
化合物(4)が、5.8g得られた(収率:81.5%)。 The residue was purified by SiO 2 - Hyflo Super Cell (2:
1, 500g) was subjected to chromatography (solvent: toluene-ethyl acetate = 7:1),
5.8g of compound (4) was obtained (yield: 81.5%).
〔化合物(4)の物理的性質〕
比旋光度:〔α〕D−10.9゜(C=0.53)
Rf値:0.60(トルエン:酢酸エチル=3:1)
1H−N.M.R.δH:7.9〜7.7(4H、m、フタロイル
基)、5.85(1H、q、J=4、11Hz、H−3)、
5.48(1H、d、J=4Hz、H−4)、5.28(1H、
d、J=8Hz、H−1)、4.52(1H、q、J=
8、11Hz、H−2)、2.36、2.19、2.06、1.85
(4個の3H、s、OAc)、1.28(48H、bs、
CH2)、0.88(6H、bt、J=6Hz、CH3)
元素分析:(C51H83O13N・C6H5CH3)
C H N
計算値(%) 68.95 9.08 1.39
実測値(%) 69.07 9.84 1.42
実施例 3
3−O−(2−アセトアミド−2−デオキシ−
β−D−ガラクトピラノシル)−1,2−ジ−
O−テトラデシル−sn−グリセロール(6)
化合物(4)(5.8g、6.3ミリモル)、n−BuNH2
(30ml)のメタノール溶液の混合物を、還流下で
19時間撹拌し、減圧留去した。残渣にメタノール
(60ml)とTHF(30ml)を加え、これに、−5〜0
℃で、無水酢酸(3ml)を滴々加えて、5℃で2
時間撹拌した。溶媒を減圧下留去し、残渣をエチ
ルエーテル(100ml)中で撹拌すると、化合物(6)
3.2gが粗固形物質として得られた(収率:73.8
%)。[Physical properties of compound (4)] Specific rotation: [α] D -10.9° (C = 0.53) Rf value: 0.60 (toluene: ethyl acetate = 3:1) 1 H-NMRδH: 7.9 to 7.7 (4H , m, phthaloyl group), 5.85 (1H, q, J=4, 11Hz, H-3),
5.48 (1H, d, J=4Hz, H-4), 5.28 (1H,
d, J=8Hz, H-1), 4.52(1H, q, J=
8, 11Hz, H-2), 2.36, 2.19, 2.06, 1.85
(4 3H, s, OAc), 1.28 (48H, bs,
CH 2 ), 0.88 (6H, bt, J=6Hz, CH 3 ) Elemental analysis: (C 51 H 83 O 13 N・C 6 H 5 CH 3 ) CH N Calculated value (%) 68.95 9.08 1.39 Actual value ( %) 69.07 9.84 1.42 Example 3 3-O-(2-acetamido-2-deoxy-
β-D-galactopyranosyl)-1,2-di-
O-tetradecyl-sn-glycerol (6) Compound (4) (5.8 g, 6.3 mmol), n-BuNH 2
(30ml) of methanol solution under reflux.
The mixture was stirred for 19 hours and evaporated under reduced pressure. Add methanol (60 ml) and THF (30 ml) to the residue, and add -5 to 0
℃, add acetic anhydride (3 ml) dropwise and dilute at 5℃ for 2 hours.
Stir for hours. The solvent was distilled off under reduced pressure and the residue was stirred in ethyl ether (100ml) to give compound (6).
3.2 g was obtained as crude solid material (yield: 73.8
%).
〔化合物(6)の物理的性質〕
m.p.:163〜165℃(メタノールより再結晶)
比旋光度:〔α〕D+1.5゜(C=0.26、ピリジン)
Rf値:0.27(CHCl3−メタノール=10:1)
13C−N.M.Rδc(DMSO−d6、80゜):101.5( 1JCH
=159.7Hz、C−1)、77.1(C−2′)、75.0(C−
5)、71.3(C−3)、70.5と70.3(L−1、L−
1′)、69.0(C−1′)、67.8(C−3′)、67.3(C
−
4)、60.2(C−6)、51.9(C−2)、
元素分析:(C39H77O8N)
C H N
計算値(%) 68.08 11.28 2.04
実測値(%) 67.72 11.38 2.23
実施例 4
3−O−(2−アセトアミド−4,6−O−ベ
ンジリデン−2−デオキシ−β−D−ガラクト
ピラノシル)−1,2−ジ−O−テトラデシル
−sn−グリセロール(7)
化合物(6)(3.2g、4.7ミリモル)とZnCl2(3.5
g)のベンズアルデヒド溶液(70ml)の混合物
を、15〜20℃で18時間撹拌した。得られた混合物
に、イソプロピルエーテル(300ml)と飽和
NH4Cl溶液(10ml)を加えた。1時間撹拌後、
沈殿した結晶を集めて、化合物(7)を2.6g得た
(収率:72%)。[Physical properties of compound (6)] mp: 163-165°C (recrystallized from methanol) Specific rotation: [α] D +1.5° (C = 0.26, pyridine) Rf value: 0.27 (CHCl 3 - methanol) = 10:1) 13 C-NMRδc (DMSO-d 6 , 80°): 101.5 ( 1 J CH
= 159.7Hz, C-1), 77.1 (C-2'), 75.0 (C-
5), 71.3 (C-3), 70.5 and 70.3 (L-1, L-
1'), 69.0 (C-1'), 67.8 (C-3'), 67.3 (C
−
4), 60.2 (C-6), 51.9 (C-2), Elemental analysis: (C 39 H 77 O 8 N) C H N Calculated value (%) 68.08 11.28 2.04 Actual value (%) 67.72 11.38 2.23 Example 4 3-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-galactopyranosyl)-1,2-di-O-tetradecyl-sn-glycerol (7) Compound ( 6) (3.2 g, 4.7 mmol) and ZnCl 2 (3.5
A mixture of benzaldehyde solution (70ml) of g) was stirred at 15-20°C for 18 hours. The resulting mixture was saturated with isopropyl ether (300 ml).
NH4Cl solution (10ml) was added. After stirring for 1 hour,
The precipitated crystals were collected to obtain 2.6 g of compound (7) (yield: 72%).
〔化合物(7)の物理的性質〕
m.p.:111〜114℃(イソプロピルエーテルから再
結晶)
比旋光度:〔α〕D−4.6゜(C=0.26)
Rf値:0.56(CHCl3−メタノール=10:1)
1H−N.M.R:7.6〜7.2(5H、m、芳香環)、6.86
(1H、d、J=5Hz、NH)、5.56(1H、s、
CHPh)、2.02(3H、s、NAc)、1.28(48H、
bs、CH2)、0.88(6H、bt、J=6Hz、CH3)
元素分析:(C46H81O8N)
C H N
計算値(%) 71.19 10.51 1.80
実測値(%) 71.18 10.56 1.80
実施例 5
3−O−〔2−アセトアミド−4,6−O−ベ
ンジリデン−2−デオキシ−3−O−(2,3,
4,6−テトラ−O−アセチル−β−D−ガラ
クトピラノシル)−β−D−ガラクトピラノシ
ル〕−1,2−ジ−O−テトラデシル−sn−グ
リセロール(9)
Hg(CN)2のベンゼン−ニトリロメタン(14:
11、85ml)溶液を蒸留して、溶媒(70ml)を留去
した。冷却したこの混合物に、室温にて化合物(7)
(790mg、1.01ミリモル)を加えた。得られた混合
物に、化合物(8)(410mg、1ミリモル)のベンゼ
ン−ニトリロメタン(1:1、2ml)溶液を、60
℃、3時間撹拌しながら滴々加え、更に、60℃で
8時間撹拌した。得られた混合物に、再び化合物
(8)(200mg、0.48ミリモル)のベンゼン−ニトロ
メタン(1:1、1ml)溶液を、1時間で滴々加
えた。得られた混合物を、更に3時間撹拌した
後、氷水に注ぎ、CH2Cl2で抽出した。有機層を、
NaHCO3溶液、水、飽和食塩水で洗浄し、減圧
下溶媒留去した。残渣を、トルエン−酢酸エチル
(1:2)を溶媒として、SiO2−ハイフロスーパ
ーセル(2:1、80g)のクロマトグラフイーに
付し、化合物(9)880mgを得た(収率:78.7%)。[Physical properties of compound (7)] mp: 111-114°C (recrystallized from isopropyl ether) Specific rotation: [α] D -4.6° (C = 0.26) Rf value: 0.56 (CHCl 3 - methanol = 10 :1) 1H -NMR: 7.6-7.2 (5H, m, aromatic ring), 6.86
(1H, d, J=5Hz, NH), 5.56 (1H, s,
CHPh), 2.02 (3H, s, NAc), 1.28 (48H,
bs, CH 2 ), 0.88 (6H, bt, J=6Hz, CH 3 ) Elemental analysis: (C 46 H 81 O 8 N) C H N Calculated value (%) 71.19 10.51 1.80 Actual value (%) 71.18 10.56 1.80 Example 5 3-O-[2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,
4,6-Tetra-O-acetyl-β-D-galactopyranosyl)-β-D-galactopyranosyl]-1,2-di-O-tetradecyl-sn-glycerol (9) Hg (CN) 2 benzene-nitrilomethane (14:
11, 85 ml) solution was distilled to remove the solvent (70 ml). Add compound (7) to this cooled mixture at room temperature.
(790 mg, 1.01 mmol) was added. A solution of compound (8) (410 mg, 1 mmol) in benzene-nitrilomethane (1:1, 2 ml) was added to the resulting mixture for 60 minutes.
The mixture was added dropwise while stirring at 60°C for 3 hours, and further stirred at 60°C for 8 hours. Add the compound again to the resulting mixture.
A solution of (8) (200 mg, 0.48 mmol) in benzene-nitromethane (1:1, 1 ml) was added dropwise over 1 hour. The resulting mixture was stirred for an additional 3 hours, then poured into ice water and extracted with CH 2 Cl 2 . organic layer,
The mixture was washed with NaHCO 3 solution, water, and saturated brine, and the solvent was distilled off under reduced pressure. The residue was subjected to chromatography on SiO 2 -Hyflo Supercel (2:1, 80 g) using toluene-ethyl acetate (1:2) as a solvent to obtain 880 mg of compound (9) (yield: 78.7 %).
〔化合物(9)の物理的性質〕
m.p.:124〜128℃(メタノールより再結晶)
比旋光度:〔α〕D+25.3゜(C=0.68)
Rf値:0.43(トルエン−酢酸エチル−メタノール
=9:9:1)
1H−N.M.R.:7.7〜7.2(5H、m、芳香環)、5.58
(1H、s、CHPh)、2.17(3H、s、OAc)、
2.05(6H、s、2個のAc)、1.99(6H、s、2
個のAc)、1.29(48H、bs、CH2)、0.88(6H、
bt、J=6Hz、CH3)
元素分析:(C60H99O17N・2CH3OH)
C H N
計算値(%) 63.62 9.21 1.20
実測値(%) 63.02 8.66 1.22
実施例 6
3−O−〔2−アセトアミド−2−デオキシ−
3−O−(β−D−ガラクトピラノシル)−β−
D−ガラクトピラノシル〕−1,2−ジ−O−
テトラデシル−sn−グリセロール(11)
化合物(9)(711mg、0.64ミリモル)とPd−C
(500mg)の酢酸(30ml)−水(10ml)溶液の混合
物を、50℃で3時間撹拌後、溶媒を減圧留去し、
さらに、トルエンを用いて、2回共沸留去した。
残渣をトリエチルアミン(5ml)−水(5ml)−メ
タノール(30ml)に溶解し、還流下で10時間撹拌
した。冷却後、沈殿した固形物を集め、化合物(11)
を455mg得た(収率83.3%)。[Physical properties of compound (9)] mp: 124-128°C (recrystallized from methanol) Specific rotation: [α] D +25.3° (C = 0.68) Rf value: 0.43 (toluene-ethyl acetate-methanol) =9:9:1) 1 H-NMR: 7.7-7.2 (5H, m, aromatic ring), 5.58
(1H, s, CHPh), 2.17 (3H, s, OAc),
2.05 (6H, s, 2 Ac), 1.99 (6H, s, 2 Ac)
Ac), 1.29 (48H, bs, CH2 ), 0.88 (6H,
bt, J=6Hz, CH 3 ) Elemental analysis: (C 60 H 99 O 17 N・2CH 3 OH) C H N Calculated value (%) 63.62 9.21 1.20 Actual value (%) 63.02 8.66 1.22 Example 6 3-O -[2-acetamido-2-deoxy-
3-O-(β-D-galactopyranosyl)-β-
D-galactopyranosyl]-1,2-di-O-
Tetradecyl-sn-glycerol (11) Compound (9) (711 mg, 0.64 mmol) and Pd-C
(500 mg) in acetic acid (30 ml) - water (10 ml) solution was stirred at 50°C for 3 hours, and the solvent was distilled off under reduced pressure.
Furthermore, azeotropic distillation was carried out twice using toluene.
The residue was dissolved in triethylamine (5 ml)-water (5 ml)-methanol (30 ml) and stirred under reflux for 10 hours. After cooling, the precipitated solid was collected and compound (11)
455 mg of was obtained (yield 83.3%).
〔化合物(11)の物理的性質〕
m.p.:216〜218℃(メタノール−水より再結晶)
比旋光度:〔α〕D+9.6°(C=0.24、ピリジン)
Rf値:0.58(CHCl3−メタノール−水=14:6:
1)
13C−N.M.Rδc(DMSO−d6、80゜):103.9( 1JCH
=156.8Hz、1b)、101.0( 1JCH=159.7Hz、1a)、
78.8(3a)、77.1(2′)、75.1(5a又は5b)、74.8(5
b
又は5a)、73.0(3b)、70.6(L−1又はL−1′)、
70.3(L−1′又はL−1,2a)、69.0(1′)、67.9
(4b、3′)、66.9(4a)、60.3(6a、6b)、51.0(2a
)
元素分析:(C45H87O13N)
C H N
計算値(%) 63.57 10.31 1.65
実測値(%) 63.59 10.35 1.56[Physical properties of compound (11)] mp: 216-218°C (recrystallized from methanol-water) Specific rotation: [α] D +9.6° (C = 0.24, pyridine) Rf value: 0.58 (CHCl 3 -methanol-water=14:6:
1) 13C -NMRδc (DMSO-d 6 , 80°): 103.9 ( 1 J CH
=156.8Hz, 1b), 101.0 ( 1 J CH =159.7Hz, 1a),
78.8 (3a), 77.1 (2′), 75.1 (5a or 5b), 74.8 (5
b
or 5a), 73.0 (3b), 70.6 (L-1 or L-1′),
70.3 (L-1' or L-1, 2a), 69.0 (1'), 67.9
(4b, 3′), 66.9 (4a), 60.3 (6a, 6b), 51.0 (2a
) Elemental analysis: (C 45 H 87 O 13 N) C H N Calculated value (%) 63.57 10.31 1.65 Actual value (%) 63.59 10.35 1.56
Claims (1)
示し、Acはアセチル基を示す。) で示されるグリセロ糖脂質化合物。 2 R2が水素である特許請求の範囲第1項記載
の化合物。 3 R2がアセチル基である特許請求の範囲第1
項記載の化合物。 4 式: で表わされる化合物(1)を、無水フタル酸で処理し
た後、アセチル化して、式: (ただし、式中、Acはアセチル基、Phthはフタ
ロイル基を示す。) で表わされる化合物(2)を得、該化合物を、ルイス
酸存在下で式: で表わされる化合物(3)と反応せしめて、式(4)で表
わされる化合物(4)を得、該化合物を、アミン類で
処理して、式(5)で表わされる化合物(5)を得、該化
合物を無水酢酸で処理して、N−アセチル化を行
つて、式(6): で表わされる化合物(6)を得、該化合物を、ルイス
酸の存在下、ベンズアルデヒドで処理して、式: (ただし、式中、Phは、フエニル基、Acは前記
に同じ。) で表わされる化合物(7)を得、該化合物を、水銀化
合物の存在下、式: (ただし、式中、Xはハロゲン原子を示し、Ac
は前記に同じ。) で表わされる化合物(8)と反応せしめて、式(9)で表
わされる化合物(9)を得、該化合物を、酸化加水分
解して脱ベンジリデン化を行つて、式(10)で表わさ
れる化合物を得、該化合物を塩基の存在下で還流
して、脱アセチル化して、式(11): (9)R1、R1=ベンジリデン、R2=アセチル基 (10)R1=水素、R2=アセチル基 (11)R1=R2=水素 (ただし、式中、Acは前記に同じ。) で表わされる化合物を得ることを特徴とする新規
グリセロ糖脂質化合物の製造法。[Claims] 1. General formula: (However, in the formula, R 2 represents hydrogen or an acetyl group, and Ac represents an acetyl group.) A glyceroglycolipid compound represented by the following. 2. The compound according to claim 1, wherein R 2 is hydrogen. 3 Claim 1 in which R 2 is an acetyl group
Compounds described in Section. 4 formula: Compound (1) represented by is treated with phthalic anhydride and then acetylated to form the formula: (However, in the formula, Ac represents an acetyl group and Phth represents a phthaloyl group.) A compound (2) represented by the following formula was obtained, and the compound was converted into the following formula in the presence of a Lewis acid: The compound (4) represented by the formula (4) is obtained by reacting with the compound (3) represented by the formula (4), and the compound (5) represented by the formula (5) is obtained by treating the compound with an amine. , the compound is treated with acetic anhydride to perform N-acetylation, resulting in formula (6): Compound (6) represented by is obtained, and this compound is treated with benzaldehyde in the presence of Lewis acid to obtain the formula: (However, in the formula, Ph is a phenyl group, and Ac is the same as above.) A compound (7) represented by (However, in the formula, X represents a halogen atom, and Ac
is the same as above. ) to obtain a compound (9) represented by formula (9), which is then debenzylidened by oxidative hydrolysis to form a compound represented by formula (10). A compound is obtained, which is deacetylated by refluxing in the presence of a base to form the formula (11): (9) R 1 , R 1 = benzylidene, R 2 = acetyl group, (10) R 1 = hydrogen, R 2 = Acetyl group (11) R 1 = R 2 = Hydrogen (However, in the formula, Ac is the same as above.) A method for producing a novel glyceroglycolipid compound, which is characterized by obtaining a compound represented by the following.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15231281A JPS5855495A (en) | 1981-09-26 | 1981-09-26 | Novel glyceroglycolipid compound and its preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15231281A JPS5855495A (en) | 1981-09-26 | 1981-09-26 | Novel glyceroglycolipid compound and its preparation |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5855495A JPS5855495A (en) | 1983-04-01 |
JPS6328074B2 true JPS6328074B2 (en) | 1988-06-07 |
Family
ID=15537766
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP15231281A Granted JPS5855495A (en) | 1981-09-26 | 1981-09-26 | Novel glyceroglycolipid compound and its preparation |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5855495A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01174281U (en) * | 1988-05-31 | 1989-12-11 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6344590A (en) * | 1986-08-12 | 1988-02-25 | Mect Corp | Production of sialic acid derivative |
-
1981
- 1981-09-26 JP JP15231281A patent/JPS5855495A/en active Granted
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01174281U (en) * | 1988-05-31 | 1989-12-11 |
Also Published As
Publication number | Publication date |
---|---|
JPS5855495A (en) | 1983-04-01 |
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