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【结 构 式】

【药物名称】OSW-1

【化学名称】16beta-[2-O-Acetyl-3-O-[2-O-(4-methoxybenzoyl)-beta-D-xylopyranosyl)-alpha-L-arabinopyranosyloxy]-3beta,17alpha-dihydroxycholest-5-en-22-one

【CA登记号】145075-81-6

【 分 子 式 】C47H68O15

【 分 子 量 】873.05701

【开发单位】Shionogi (Originator), University of Tokyo (Originator)

【药理作用】ONCOLYTIC DRUGS, Antiestrogens

合成路线1合成路线2合成路线3合成路线4合成路线5合成路线6合成路线7合成路线8合成路线9合成路线10合成路线11合成路线12合成路线13合成路线14合成路线15合成路线16合成路线17

合成路线1

Synthesis of intermediate monosaccharide (VIII): The reaction of the tetraacetyl-L-arabinose (I) with Ph-SH and SnCl4 gives the thioglycoside (II), which is deacetylated with NaOMe in methanol, yielding compound (III). The reaction of (III) with 2,2-dimethoxypropane (IV) and CSA in dichloromethane affords the acetonide (V), which is acetylated with Ac2O, DMAP and TEA to provide the acetate (VI). Elimination of the acetonide group of (VI) with Amberlite IR-118B furnishes diol (VII), which is selectively silylated with Tes-OTf and lutidine in dichloromethane to afford the desired intermediate monosaccharide (VIII).

参考文献 中间体
【1】 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 48936 D-Arabinose tetraacetate C13H18O9 详情 详情
(II) 48937 (2S,3R,4S,5S)-3,5-bis(acetoxy)-2-(phenylsulfanyl)tetrahydro-2H-pyran-4-yl acetate C17H20O7S 详情 详情
(III) 48938 (2S,3R,4S,5S)-2-(phenylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol C11H14O4S 详情 详情
(IV) 10722 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane 77-76-9 C5H12O2 详情 详情
(V) 48939 (3aS,6S,7R,7aR)-2,2-dimethyl-6-(phenylsulfanyl)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-ol C14H18O4S 详情 详情
(VI) 48940 (3aS,6S,7R,7aS)-2,2-dimethyl-6-(phenylsulfanyl)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-yl acetate C16H20O5S 详情 详情
(VII) 48941 (2S,3R,4S,5S)-4,5-dihydroxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl acetate C13H16O5S 详情 详情
(VIII) 48942 (2S,3R,4R,5S)-4-hydroxy-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl acetate C19H30O5SSi 详情 详情

合成路线2

Synthesis of intermediate monosaccharide (XVIII): The reaction of tetraacetyl-D-xylose (IX) with HBr in HOAc gives the bromoglycoside (X), which by reaction with ethylmercaptane and lutidine yields the thio orthoester (XI). Hydrolysis of (XI) with NaOMe in methanol affords the deacetylated compound (XII), which is protected with Pmb-Cl and NaH to provide the diether (XIII). The cleavage of the cyclic thio orthoester with ZnCl2 in dichloromethane gives the 2-O-acetyl-thioglycoside (XIV), which is hydrolyzed with NaOMe in methanol to yield the alcohol (XV). Esterification of (XV) with 4-methoxybenzoyl chloride (XVI), DMAP and TEA affords the benzoate ester (XVII), which is finally converted into the target acetimidate (XVIII) by reaction with NBS in dichloromethane/water, and then with trichloroacetonitrile and DBU in the same solvent.

参考文献 中间体
【1】 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IX) 48943 (3R,4S,5R)-2,3,5-tris(acetoxy)tetrahydro-2H-pyran-4-yl acetate C13H18O9 详情 详情
(X) 23761 (2R,3R,4S,5R)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate C11H15BrO7 详情 详情
(XI) 48944 (2S,3aR,6R,7S,7aR)-6-(acetoxy)-2-(ethylsulfanyl)-2-methyltetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl acetate C13H20O7S 详情 详情
(XII) 48945 (2S,3aR,6R,7S,7aR)-2-(ethylsulfanyl)-2-methyltetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-6,7-diol C9H16O5S 详情 详情
(XIII) 48946 (2S,3aR,6R,7S,7aR)-2-(ethylsulfanyl)-6-[(4-methoxybenzyl)oxy]-2-methyltetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl 4-methoxybenzyl ether; (2S,3aR,6R,7S,7aR)-2-(ethylsulfanyl)-6,7-bis[(4-methoxybenzyl)oxy]-2-methyltetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran C25H32O7S 详情 详情
(XIV) 48947 (2R,3R,4S,5R)-2-(ethylsulfanyl)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl acetate C25H32O7S 详情 详情
(XV) 48948 (2S,3R,4R,5R)-2-(ethylsulfanyl)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-ol C23H30O6S 详情 详情
(XVI) 22671 4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride 100-07-2 C8H7ClO2 详情 详情
(XVII) 48949 (2S,3R,4S,5R)-2-(ethylsulfanyl)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H36O8S 详情 详情
(XVIII) 48950 (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H32Cl3NO9 详情 详情

合成路线3

Synthesis of intermediate disaccharide (XX): The condensation of intermediate monosaccharide (VIII) with intermediate acetimidate (XVIII) by means of BF3/Et2O gives the disaccharide (XIX), which is converted into the desired acetimidate (XX) by reaction with NBS and trichloroacetonitrile and DBU in dichloromethane/water.

参考文献 中间体
【1】 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIII) 48942 (2S,3R,4R,5S)-4-hydroxy-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl acetate C19H30O5SSi 详情 详情
(XVIII) 48950 (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H32Cl3NO9 详情 详情
(XIX) 48951 (2S,3R,4S,5R)-2-([(2S,3R,4R,5S)-3-(acetoxy)-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C48H60O13SSi 详情 详情
(XX) 48952 (2S,3R,4S,5R)-2-([(3R,4R,5S)-3-(acetoxy)-2-[(2,2,2-trichloroethanimidoyl)oxy]-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C44H56Cl3NO14Si 详情 详情

合成路线4

Synthesis of the intermediate vinyl cuprate (XXV): The reaction of cyclohexyloxyacetylene (XXI) with iso-butyl triflate (XXII) by means of BuLi gives the adduct (XXIII), which is brominated with Tms-Br, yielding the vinyl bromide (XXIV). Finally, this compound is treated with CuCN, LiCl and tBuLi in THF to afford the desired vinyl cuprate intermediate (XXV).

参考文献 中间体
【1】 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXI) 48953 1-(ethynyloxy)cyclohexane; cyclohexyl ethynyl ether C8H12O 详情 详情
(XXII) 48954 isobutyl trifluoromethanesulfonate C5H9F3O3S 详情 详情
(XXIII) 48955 1-[(4-methyl-1-pentynyl)oxy]cyclohexane; cyclohexyl 4-methyl-1-pentynyl ether C12H20O 详情 详情
(XXIV) 48956 (E)-1-bromo-4-methyl-1-pentenyl cyclohexyl ether; 1-[[(E)-1-bromo-4-methyl-1-pentenyl]oxy]cyclohexane C12H21BrO 详情 详情
(XXV) 48957 　 C54H99CuNO4 详情 详情

合成路线5

Synthesis of the cholestane aglycon (XXXVI): The protection of the OH group of dehydroisoandrosterone (XXVI) with Tbdms-Cl and imidazole gives the silyl ether (XXVII), which is condensed with ethyl triphenylphosphonium bromide (XXVIII) and potassium tert-butoxide in refluxing THF to yield the ethylidene compound (XXIX). The hydroxylation of (XXIX) with SeO2 and TBHP affords the 16alpha-hydroxy compound (XXX), which by a Swern oxidation is converted into the ketone (XXXI). The condensation of (XXXI) with the intermediate cuprate (XXV) provides the adduct (XXXII), which is treated with ethyleneglycol (XXXIII) and PPTS to give the spiroketal (XXXIV). The oxidative cleavage of the enol acetate of (XXXIV) with tBu-OK and Davis reagent yields the alpha-hydroxyketone (XXXV), which is finally reduced with LiAlH4 to afford the desired cholestane aglycon (XXXVI).

参考文献 中间体
【1】 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXV) 48957 　 C54H99CuNO4 详情 详情
(XXVI) 11713 Dehydroepiandrosterone;prasterone；(3S,8R,9S,10R,13S,14S)-3-Hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one 53-43-0 C19H28O2 详情 详情
(XXVII) 16818 (3S,8R,9S,10R,13S,14S)-3-[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one C25H42O2Si 详情 详情
(XXVIII) 11717 Ethyl(triphenyl)phosphonium bromide; (Ethyl)triphenylphosphonium bromide 1530-32-1 C20H20BrP 详情 详情
(XXIX) 48958 tert-butyl(dimethyl)silyl (3S,10R,13S)-17-[(Z)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-yl ether; tert-butyl([(3S,10R,13S)-17-[(Z)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-yl]oxy)dimethylsilane C27H46OSi 详情 详情
(XXX) 48959 (3S,10R,13S,16R)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(E)ethylidene]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-16-ol C27H46O2Si 详情 详情
(XXXI) 48960 (3S,10R,13S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(E)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,17-tetradecahydro-16H-cyclopenta[a]phenanthren-16-one C27H44O2Si 详情 详情
(XXXII) 48961 (3S,10R,13S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(1S,2Z)-2-(cyclohexyloxy)-1,5-dimethyl-2-hexenyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate C41H68O4Si 详情 详情
(XXXIII) 11295 Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol 107-21-1 C2H6O2 详情 详情
(XXXIV) 48962 (3S,10R,13S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate C37H62O5Si 详情 详情
(XXXV) 48963 (3S,10R,13S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-hydroxy-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,17-tetradecahydro-16H-cyclopenta[a]phenanthren-16-one C35H60O5Si 详情 详情
(XXXVI) 48964 (3S,10R,13S,16S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol C35H62O5Si 详情 详情

合成路线6

Final assembly of the target compound: The condensation of the intermediate aglycon (XXXVI) with the intermediate disaccharide (XX) by means of Tms-OTf in dichloromethane gives the protected adduct (XXXVII), which is finally treated first with DDQ and then with Pd(MeCN)2Cl2 in acetone/water to obtain the target saponin, OSW-1.

参考文献 中间体
【1】 Jin, Z.; Yu, W.; A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: Total synthesis of a highly potent antitumor natural product OSW-1. J Am Chem Soc 2001, 123, 14, 3369.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XX) 48952 (2S,3R,4S,5R)-2-([(3R,4R,5S)-3-(acetoxy)-2-[(2,2,2-trichloroethanimidoyl)oxy]-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C44H56Cl3NO14Si 详情 详情
(XXXVI) 48964 (3S,10R,13S,16S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol C35H62O5Si 详情 详情
(XXXVII) 48965 (2S,3R,4S,5R)-2-([(2S,3R,4R,5S)-3-(acetoxy)-2-([(3S,10R,13S,16S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-hydroxy-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-16-yl]oxy)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C77H116O18Si2 详情 详情

合成路线7

Synthesis of intermediate monosaccharide (VI): The reaction of L-arabinose (I) with benzyl alcohol and HCl (gas) gives 1-O-benzyl-L-arabinose (II), which is treated with 2,2-dimethoxypropane (III) and TsOH to yield the 3,4-O-isopropylidene derivative (IV). The selective acetylation of (IV) with Ac2O and pyridine affords the 2-O-acetyl derivative (V), which is finally treated with HOAc in hot water to provide the intermediate 2-O-acetyl-1-O-benzyl-L-arabinose (VI).

参考文献 中间体
【1】 Deng, S.; et al.; First total synthesis of an exceptionally potent antitumor saponin, OSW-1. J Org Chem 1999, 64, 1, 202.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 17520 (3R,4S,5S)tetrahydro-2H-pyran-2,3,4,5-tetrol; L-(+)-Arabinose 7296-56-2 C5H10O5 详情 详情
(II) 48966 2-Benzyloxytetrahydropyran-3,4,5-triol C12H16O5 详情 详情
(III) 10722 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane 77-76-9 C5H12O2 详情 详情
(IV) 48967 (3aS,6S,7R,7aR)-6-(benzyloxy)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-ol C15H20O5 详情 详情
(V) 48968 (3aS,6S,7R,7aS)-6-(benzyloxy)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-yl acetate C17H22O6 详情 详情
(VI) 48969 (2S,3R,4S,5S)-2-(benzyloxy)-4,5-dihydroxytetrahydro-2H-pyran-3-yl acetate C14H18O6 详情 详情

合成路线8

Synthesis of intermediate monosaccharide (XIII): The reaction of D-xylose (VII) with benzyl alcohol and HCl (gas) gives the 1-O-benzyl-D-xylose (VIII), which is regioselectively acylated with 4-methoxybenzoyl chloride (IX) and pyridine to yield 1-O-benzyl-2-O-(4-methoxybenzoyl)-D-xylose (X). The silylation of (X) with Tes-Cl and imidazole in DMF affords the disilylated compound (XI), which is debenzylated by hydrogenation with H2 over Pd/C in ethyl acetate to provide 2-O-(4-methoxybenzoyl)-3,4-O-bis(triethylsilyl)-D-xylose (XII). Finally, this compound is converted into the target trichloroacetimidate (XIII) by reaction with trichloroacetonitrile and DBU in dichloromethane.

参考文献 中间体
【1】 Deng, S.; et al.; First total synthesis of an exceptionally potent antitumor saponin, OSW-1. J Org Chem 1999, 64, 1, 202.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VII) 48970 2,3,4,5-Tetrahydroxypentanal; D-xylopyranose; D-(+)-Xylose; D-xylose; D-(+)-Wood Sugar; Xylose; Wood Sugar 58-86-6 C5H10O5 详情 详情
(VIII) 48971 (3R,4S,5R)-2-(benzyloxy)tetrahydro-2H-pyran-3,4,5-triol C12H16O5 详情 详情
(IX) 22671 4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride 100-07-2 C8H7ClO2 详情 详情
(X) 48972 (3R,4S,5R)-2-(benzyloxy)-4,5-dihydroxytetrahydro-2H-pyran-3-yl 4-methoxybenzoate C20H22O7 详情 详情
(XI) 48973 (3R,4R,5R)-2-(benzyloxy)-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C32H50O7Si2 详情 详情
(XII) 48974 (3R,4R,5R)-2-hydroxy-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C25H44O7Si2 详情 详情
(XIII) 48975 (3R,4R,5R)-2-[(2,2,2-trichloroethanimidoyl)oxy]-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C27H44Cl3NO7Si2 详情 详情

合成路线9

Synthesis of intermediate disaccharide (XVII): The regioselective glycosylation of intermediate arabinose derivative (VI) with the intermediate acetimidate (XIII) by means of BF3/Et2O gives the disaccharide (XIV), which is silylated with Tes-OTf and lutidine in dichloromethane to yield the fully protected disaccharide (XV). Elimination of the benzyl protecting group of (XV) by hydrogenation with H2 over Pd/C in hot ethyl acetate affords the hemiacetal (XVI), which is converted into the target trichloroacetimidate (XVII) by reaction with trichloroacetonitrile and DBU in dichloromethane.

参考文献 中间体
【1】 Deng, S.; et al.; First total synthesis of an exceptionally potent antitumor saponin, OSW-1. J Org Chem 1999, 64, 1, 202.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 48969 (2S,3R,4S,5S)-2-(benzyloxy)-4,5-dihydroxytetrahydro-2H-pyran-3-yl acetate C14H18O6 详情 详情
(XIII) 48975 (3R,4R,5R)-2-[(2,2,2-trichloroethanimidoyl)oxy]-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C27H44Cl3NO7Si2 详情 详情
(XIV) 48976 (2S,3R,4R,5R)-2-[[(2S,3R,4S,5S)-3-(acetoxy)-2-(benzyloxy)-5-hydroxytetrahydro-2H-pyran-4-yl]oxy]-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C39H60O12Si2 详情 详情
(XV) 48977 (2S,3R,4R,5R)-2-([(2S,3R,4R,5S)-3-(acetoxy)-2-(benzyloxy)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C45H74O12Si3 详情 详情
(XVI) 48978 (2S,3R,4R,5R)-2-([(3R,4R,5S)-3-(acetoxy)-2-hydroxy-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C38H68O12Si3 详情 详情
(XVII) 48979 (2S,3R,4R,5R)-2-([(3R,4R,5S)-3-(acetoxy)-2-[(2,2,2-trichloroethanimidoyl)oxy]-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C40H68Cl3NO12Si3 详情 详情

合成路线10

Synthesis of the cholestane aglycone (XXXII): The condensation of the commercial dehydroisoandrosterone (XVIII) with ethyl triphenylphosphonium bromide (XIX) and potassium tert-butoxide in refluxing THF gives the ethylidene derivative (XX), which is silylated at the 3-OH group with Tbdps-Cl and imidazole to yield the silyl ether (XXI). The reaction of (XXI) with paraformaldehyde in the presence of catalytic BF3/Et2O affords the desired homoallylic alcohol (XXII) stereoselectively. Oxidation of alcohol (XXII) with DMP in dichloromethane provides the corresponding aldehyde (XXIII), which when treated with the Grignard reagent (XXIV) of the 1-bromo-3-methyl butane in ether furnishes the adduct (XXV). The oxidation of the secondary alcohol of (XXV) with PDC in DMF/dichloromethane gives the expected ketone (XXVI), which is protected as the spiroketal (XXVIII) by reaction with ethyleneglycol (XXVII), TsOH and triethyl orthoformate. The Tbdps protecting group of (XXVIII) was now converted into the Tbdms group by desilylation with TBAF and resilylation with Tbdms-Cl and imidazole to give (XXIX). The oxidation of (XXIX) with OsO4 and pyridine in ether yields the 16alpha,17alpha-diol (XXX), which is oxidized with oxalyl chloride to afford the ketone (XXXI). The reduction of (XXXI) with NaBH4 and CeCl3 in THF provides the target 16beta,17alpha-diol (XXXII).

参考文献 中间体
【1】 Deng, S.; et al.; First total synthesis of an exceptionally potent antitumor saponin, OSW-1. J Org Chem 1999, 64, 1, 202.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XVIII) 11713 Dehydroepiandrosterone;prasterone；(3S,8R,9S,10R,13S,14S)-3-Hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one 53-43-0 C19H28O2 详情 详情
(XIX) 11717 Ethyl(triphenyl)phosphonium bromide; (Ethyl)triphenylphosphonium bromide 1530-32-1 C20H20BrP 详情 详情
(XX) 48980 (3S,10R,13S)-17-[(Z)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-ol C21H32O 详情 详情
(XXI) 48981 tert-butyl([(3S,10R,13S)-17-[(Z)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-yl]oxy)diphenylsilane; tert-butyl(diphenyl)silyl (3S,10R,13S)-17-[(Z)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-yl ether C37H50OSi 详情 详情
(XXII) 48982 (2S)-2-((3S,10R,13S)-3-[[tert-butyl(diphenyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)-1-propanol C38H52O2Si 详情 详情
(XXIII) 48983 (2S)-2-((3S,10R,13S)-3-[[tert-butyl(diphenyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)propanal C38H50O2Si 详情 详情
(XXIV) 13532 Bromo(isopentyl)magnesium C5H11BrMg 详情 详情
(XXV) 48984 (2S,3S)-2-((3S,10R,13S)-3-[[tert-butyl(diphenyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)-6-methyl-3-heptanol C43H62O2Si 详情 详情
(XXVI) 48985 (2S)-2-((3S,10R,13S)-3-[[tert-butyl(diphenyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)-6-methyl-3-heptanone C43H60O2Si 详情 详情
(XXVII) 11295 Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol 107-21-1 C2H6O2 详情 详情
(XXVIII) 48986 tert-butyl([(3S,10R,13S)-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy)diphenylsilane; tert-butyl(diphenyl)silyl (3S,10R,13S)-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl ether C45H64O3Si 详情 详情
(XXIX) 48987 tert-butyl([(3S,10R,13S)-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy)dimethylsilane; tert-butyl(dimethyl)silyl (3S,10R,13S)-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl ether C35H60O3Si 详情 详情
(XXX) 48988 (3S,10R,13S,16R,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol C35H62O5Si 详情 详情
(XXXI) 48963 (3S,10R,13S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-hydroxy-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,17-tetradecahydro-16H-cyclopenta[a]phenanthren-16-one C35H60O5Si 详情 详情
(XXXII) 48964 (3S,10R,13S,16S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol C35H62O5Si 详情 详情

合成路线11

Final assembly of the target compound: The condensation of the intermediate aglycon (XXXII) with the intermediate disaccharide (XVII) by means of Tms-OTf in dichloromethane gives the protected adduct (XXXIII), which is finally treated with Pd(MeCN)2Cl2 in acetone/water to obtain the target saponin, OSW-1.

参考文献 中间体
【1】 Deng, S.; et al.; First total synthesis of an exceptionally potent antitumor saponin, OSW-1. J Org Chem 1999, 64, 1, 202.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XVII) 48979 (2S,3R,4R,5R)-2-([(3R,4R,5S)-3-(acetoxy)-2-[(2,2,2-trichloroethanimidoyl)oxy]-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C40H68Cl3NO12Si3 详情 详情
(XXXII) 48964 (3S,10R,13S,16S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol C35H62O5Si 详情 详情
(XXXIII) 48989 (2S,3R,4R,5R)-2-([(2S,3R,4R,5S)-3-(acetoxy)-2-([(3S,10R,13S,16S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-hydroxy-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-16-yl]oxy)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C73H128O16Si4 详情 详情

合成路线12

. L- Arabinose monosaccharide intermediate (VIII): The reaction of tetraacetyl-L-arabinose (I) with Ph-SH by means of SnCl4 in dichloromethane gives the acetylated thioglycoside (II), which is deacetylated by means of NaOMe in methanol to yield thioglycoside (III). The reaction of (III) with 2,2-dimethoxypropane (IV) and CSA in dichloromethane affords the acetonide (V), which is acetylated with Ac2O, TEA and DMAP to provide monoacetate (VI). The cleavage of the acetonide group of (VI) by means of Amberlite IR-118H leads to the monoacetylated thioglycoside (VII), which is finally selectively monosilylated with Tms-OTf and lutidine in dichloromethane the target L-arabinose intermediate (VIII)

参考文献 中间体
【1】 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 48936 D-Arabinose tetraacetate C13H18O9 详情 详情
(II) 48937 (2S,3R,4S,5S)-3,5-bis(acetoxy)-2-(phenylsulfanyl)tetrahydro-2H-pyran-4-yl acetate C17H20O7S 详情 详情
(III) 48938 (2S,3R,4S,5S)-2-(phenylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol C11H14O4S 详情 详情
(IV) 10722 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane 77-76-9 C5H12O2 详情 详情
(V) 48939 (3aS,6S,7R,7aR)-2,2-dimethyl-6-(phenylsulfanyl)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-ol C14H18O4S 详情 详情
(VI) 48940 (3aS,6S,7R,7aS)-2,2-dimethyl-6-(phenylsulfanyl)tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-yl acetate C16H20O5S 详情 详情
(VII) 48941 (2S,3R,4S,5S)-4,5-dihydroxy-2-(phenylsulfanyl)tetrahydro-2H-pyran-3-yl acetate C13H16O5S 详情 详情
(VIII) 48942 (2S,3R,4R,5S)-4-hydroxy-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl acetate C19H30O5SSi 详情 详情

合成路线13

D-xylose trichloroacetimidate intermediate (XVIII): The reaction of tetraacetyl-D-xylose (IX) with HBr/AcOH n dichloromethane gives the glycosyl bromide (X), which is treated with Et-SH and lutidine in nitromethane to yield the thio orthoester (XI). The deacetylation of (XI) by means of NaOMe in methanol affords dihydroxy compound (XII), whose OH groups are protected by means of Pmb-Cl and NaH to provide the bis 4-methoxybenzyl ether compound (XIII). ZnCl2 promoted ring opening of the thio orthoester group of (XIII) leads to the thioglycoside (XIV), which is deacetylated by means of NaOMe in methanol to give compound (XV). The acylation of the free OH group of (XV) with 4-methoxybenzoyl chloride (XVI), TEA and DMAP in dichloromethane yields the benzoate ester (XVII), which is finally converted into the target D-xylose trichloroacetimidate (XVIII) by reaction with NBS, Cl3C-CN and DBU in dichloromethane

参考文献 中间体
【1】 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IX) 48936 D-Arabinose tetraacetate C13H18O9 详情 详情
(X) 23761 (2R,3R,4S,5R)-3,5-bis(acetoxy)-2-bromotetrahydro-2H-pyran-4-yl acetate C11H15BrO7 详情 详情
(XI) 60144 (2S,3aR,6R,7S,7aR)-6-(acetyloxy)-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl acetate C14H22O7S 详情 详情
(XII) 60145 (2S,3aR,6R,7S,7aR)-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-6,7-diol C10H18O5S 详情 详情
(XIII) 60146 (2S,3aR,6R,7S,7aR)-6,7-bis[(4-methoxybenzyl)oxy]-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran; (2S,3aR,6R,7S,7aR)-6-[(4-methoxybenzyl)oxy]-2-methyl-2-(propylsulfanyl)tetrahydro-3aH-[1,3]dioxolo[4,5-b]pyran-7-yl 4-methoxybenzyl ether C26H34O7S 详情 详情
(XIV) 60147 (2S,3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-yl acetate C26H34O7S 详情 详情
(XV) 60149 (2S,3R,4R,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-ol C24H32O6S 详情 详情
(XVI) 60148 4-methoxybenzoic acid C8H8O3 详情 详情
(XVII) 60150 (2S,3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-(propylsulfanyl)tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C32H38O8S 详情 详情
(XVIII) 48950 (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H32Cl3NO9 详情 详情

合成路线14

Intermediate beta-disaccharide trichloroacetimidate (XX): The glycosylation of intermediate (VIII) with intermediate (XVIII) by means of BF3/Et2O in dichloromethane gives the beta-disaccharide (XIX), which is converted into the target trichloroacetimidate (XX) by reaction with NBS, Cl3C-CN and DBU in dichloromethane

参考文献 中间体
【1】 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VIII) 48942 (2S,3R,4R,5S)-4-hydroxy-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-3-yl acetate C19H30O5SSi 详情 详情
(XVIII) 48950 (3R,4S,5R)-4,5-bis[(4-methoxybenzyl)oxy]-2-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C31H32Cl3NO9 详情 详情
(XIX) 48951 (2S,3R,4S,5R)-2-([(2S,3R,4R,5S)-3-(acetoxy)-2-(phenylsulfanyl)-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl]oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C48H60O13SSi 详情 详情
(XX) 60151 (2S,3R,4S,5R)-2-({(2S,3R,4R,5S)-3-(acetyloxy)-2-[(2,2,2-trichloroethanimidoyl)oxy]-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl}oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C44H56Cl3NO14Si 详情 详情

合成路线15

Alpha-(cyclohexloxy)vinyl bromide (XXIV): The reaction of (cyclohexyloxy)acetylene (XXI) with isobutyl triflate (XXII) by means of BuLi gives 1-(cyclohexyloxy)-4-methyl-1-pentyne (XXIII), which is then brominated to the target vinyl bromide (XXIV) by means of Tms-Br in methanol

参考文献 中间体
【1】 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXI) 48953 1-(ethynyloxy)cyclohexane; cyclohexyl ethynyl ether C8H12O 详情 详情
(XXII) 48954 isobutyl trifluoromethanesulfonate C5H9F3O3S 详情 详情
(XXIII) 48955 1-[(4-methyl-1-pentynyl)oxy]cyclohexane; cyclohexyl 4-methyl-1-pentynyl ether C12H20O 详情 详情
(XXIV) 48956 (E)-1-bromo-4-methyl-1-pentenyl cyclohexyl ether; 1-[[(E)-1-bromo-4-methyl-1-pentenyl]oxy]cyclohexane C12H21BrO 详情 详情

合成路线16

Synthesis of the target cholestane glycoside. The reaction of 3-beta-hydroxy-5-androsten-17-one (XXV) with Tbdms-Cl gives the silyl ether (XXVI), which is condensed with phosphorane (XXVII), yielding the ethylidene derivative (XXVIII). The oxidation of (XXVIII) by means of SeO2 and tert-butyl hydroperoxide affords the alcohol (XXIX), which is submitted to a Swern oxidation to provide the enone (XXX). The condensation of (XXX) with the intermediate vinyl bromide (XXIV) by means of CuCN, LiCl and Tms-Cl gives the non isolated intermediate (XXXI), which is treated with acetyl chloride to yield the enol acetate (XXXII). The reaction of (XXXII) with ethyleneglycol and PPTS in dichloromethane affords the ethylene ketal (XXXIII), which is submitted to a stereoselective oxidation with Davis reagent and t-BuOK to provide the hydroxy ketone (XXXIV). The stereoselective reduction of (XXXIV) by means of LiAlH4 in dichloromethane leads to the dihydroxy compound (XXXV).

参考文献 中间体
【1】 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 11295 Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol 107-21-1 C2H6O2 详情 详情
(XXIV) 48956 (E)-1-bromo-4-methyl-1-pentenyl cyclohexyl ether; 1-[[(E)-1-bromo-4-methyl-1-pentenyl]oxy]cyclohexane C12H21BrO 详情 详情
(XXV) 11713 Dehydroepiandrosterone;prasterone；(3S,8R,9S,10R,13S,14S)-3-Hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one 53-43-0 C19H28O2 详情 详情
(XXVI) 16818 (3S,8R,9S,10R,13S,14S)-3-[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one C25H42O2Si 详情 详情
(XXVII) 60152 ethylidene(triphenyl)phosphorane C20H19P 详情 详情
(XXVIII) 60153 tert-butyl(dimethyl)silyl (3S,8S,9S,10R,13S,14S)-17-[(Z)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-yl ether; tert-butyl({(3S,8S,9S,10R,13S,14S)-17-[(Z)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-3-yl}oxy)dimethylsilane C27H46OSi 详情 详情
(XXIX) 60154 (3S,8R,9S,10R,13S,14S,16R)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-[(E)ethylidene]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-16-ol C27H46O2Si 详情 详情
(XXX) 60155 (3S,8R,9S,10R,13S,14S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-[(E)ethylidene]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,17-tetradecahydro-16H-cyclopenta[a]phenanthren-16-one C27H44O2Si 详情 详情
(XXXI) 60156 tert-butyl(dimethyl)silyl (3S,8R,9S,10R,13S,14S)-17-[(1S,2Z)-2-(cyclohexyloxy)-1,5-dimethyl-2-hexenyl]-10,13-dimethyl-16-[(trimethylsilyl)oxy]-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl ether; tert-butyl({(3S,8R,9S,10R,13S,14S)-17-[(1S,2Z)-2-(cyclohexyloxy)-1,5-dimethyl-2-hexenyl]-10,13-dimethyl-16-[(trimethylsilyl)oxy]-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl}oxy)dimethylsilane C42H74O3Si2 详情 详情
(XXXII) 60157 (3S,8R,9S,10R,13S,14S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-[(1S,2Z)-2-(cyclohexyloxy)-1,5-dimethyl-2-hexenyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate C41H68O4Si 详情 详情
(XXXIII) 60158 (3S,8R,9S,10R,13S,14S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate C37H62O5Si 详情 详情
(XXXIV) 60159 (3S,8R,9S,10R,13S,14S,17S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-hydroxy-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,17-tetradecahydro-16H-cyclopenta[a]phenanthren-16-one C35H60O5Si 详情 详情
(XXXV) 60160 (3S,8R,9S,10R,13S,14S,16S,17S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol C35H62O5Si 详情 详情

合成路线17

Coupling of the steroid aglycon (XXXV) with the intermediate disaccharide (XX) by means of Tms-OTf in dichloromethane gives the glycoside (XXXVI), which is finally deprotected by reaction sequentially with DDQ and with Pd(CH3CN)2Cl2 to yield the target cholestane glycoside

参考文献 中间体
【1】 Yu, W.; Jin, Z.; Total synthesis of the anticancer natural product OSW-1. J Am Chem Soc 2002, 124, 23, 6576.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XX) 60151 (2S,3R,4S,5R)-2-({(2S,3R,4R,5S)-3-(acetyloxy)-2-[(2,2,2-trichloroethanimidoyl)oxy]-5-[(triethylsilyl)oxy]tetrahydro-2H-pyran-4-yl}oxy)-4,5-bis[(4-methoxybenzyl)oxy]tetrahydro-2H-pyran-3-yl 4-methoxybenzoate C44H56Cl3NO14Si 详情 详情
(XXXV) 60160 (3S,8R,9S,10R,13S,14S,16S,17S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol C35H62O5Si 详情 详情
(XXXVI) 60161 (2S,3R,4S,5R)-2-({(2S,3R,4R,5S)-3-(acetyloxy)-2-({(3S,8R,9S,10R,13S,14S,16S,17S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-hydroxy-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cycl C77H116O18Si2 详情 详情
Extended Information