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【结 构 式】

【分子编号】30279

【品名】methyl (1S,9R)-14-oxotricyclo[7.4.1.0(1,5)]tetradeca-4,6-diene-7-carboxylate

【CA登记号】

【 分 子 式 】C16H20O3

【 分 子 量 】260.333

【元素组成】C 73.82% H 7.74% O 18.44%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IV)

The known photoaddition-fragmentation product (I) was brominated with N-bromosuccinimide in the presence of AIBN to afford bromoester (II), which upon treatment with LiCl in refluxing DMF produced the unsaturated ester (III) with concomitant removal of the methyl carbonate. Subsequent mesylation of the hydroxyl group of (III), followed by elimination with DBU in boiling benzene led to the formation of the diene ester (IV). Selective epoxidation of (IV) with m-chloroperbenzoic acid yielded the epoxy-unsaturated ester (V), which was oxidized with OsO4 and N-methylmorpholine-N-oxide to the epoxy diol (VI). Reaction of (VI) with camphorsulfonic acid in wet CH2Cl2 gave the corresponding tetraol, which on exposure to p-anisaldehyde dimethyl acetal (VII) produced selectively the acetal (VIII). The reduction of the ester group of (VIII) with LiAlH4, followed by silylation with TBDPSi-Cl afforded the monosilylated compound (IX). The reaction of (IX) with SOCl2 in the presence of pyridine generated the cyclic sulfite ester (X), which was oxidized to sulfate (XI) using RuCl3 and NaIO4.

1 Winkler, J.D.; Lewin, N.E.; Blumberg, P.M.; Harrison, S.; Kim, S.; Synthesis and biological evaluation of highly functionalized analogues of ingenol. J Am Chem Soc 1999, 121, 2, 296.
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) 30276 methyl (1S,4S,5S,9R)-4-[(methoxycarbonyl)oxy]-14-oxotricyclo[7.4.1.0(1,5)]tetradecane-7-carboxylate C18H26O6 详情 详情
(II) 30277 methyl (1S,4S,5S,9R)-6-bromo-4-[(methoxycarbonyl)oxy]-14-oxotricyclo[7.4.1.0(1,5)]tetradecane-7-carboxylate C18H25BrO6 详情 详情
(III) 30278 methyl (1S,4S,5S,9R)-4-hydroxy-14-oxotricyclo[7.4.1.0(1,5)]tetradec-6-ene-7-carboxylate C16H22O4 详情 详情
(IV) 30279 methyl (1S,9R)-14-oxotricyclo[7.4.1.0(1,5)]tetradeca-4,6-diene-7-carboxylate C16H20O3 详情 详情
(V) 30280 methyl (1S,4S,6R,10R)-15-oxo-5-oxatetracyclo[8.4.1.0(1,6).0(4,6)]pentadec-7-ene-8-carboxylate C16H20O4 详情 详情
(VI) 30281 methyl (1S,4S,6S,7R,8R,10R)-7,8-dihydroxy-15-oxo-5-oxatetracyclo[8.4.1.0(1,6).0(4,6)]pentadecane-8-carboxylate C16H22O6 详情 详情
(VII) 26485 1-(dimethoxymethyl)-4-methoxybenzene 2186-92-7 C10H14O3 详情 详情
(VIII) 30282 methyl (1S,6R,8R,9S,11R,13R,16S)-8,16-dihydroxy-11-(4-methoxyphenyl)-17-oxo-10,12-dioxatetracyclo[7.6.1.1(1,6).0(13,16)]heptadecane-8-carboxylate C24H30O8 详情 详情
(IX) 30283 (1S,6R,8S,9R,11S,13R,16S)-8-([[tert-butyl(diphenyl)silyl]oxy]methyl)-8,16-dihydroxy-11-(4-methoxyphenyl)-10,12-dioxatetracyclo[7.6.1.1(1,6).0(13,16)]heptadecan-17-one C39H48O7Si 详情 详情
(X) 30284 (1S,4R,6R,8S,9S,13S,15R)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-6-(4-methoxyphenyl)-5,7,10,12-tetraoxa-11lambda(4)-thiapentacyclo[13.4.1.0(1,9).0(4,9).0(8,13)]icosane-11,20-dione C39H46O8SSi 详情 详情
(XI) 30285 (1S,4R,6R,8S,9S,13S,15R)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-6-(4-methoxyphenyl)-5,7,10,12-tetraoxa-11lambda(6)-thiapentacyclo[13.4.1.0(1,9).0(4,9).0(8,13)]icosane-11,11,20-trione C39H46O9SSi 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

The known photoaddition-fragmentation product (I) was brominated with N-bromosuccinimide in the presence of AIBN to afford bromoester (II), which upon treatment with LiCl in refluxing DMF produced the unsaturated ester (III) with concomitant removal of the methyl carbonate. Subsequent mesylation of the hydroxyl group of (III), followed by elimination with DBU in boiling benzene led to the formation of the diene ester (IV). Selective epoxidation with m-chloroperbenzoic acid yielded the epoxy-unsaturated ester (V), which was oxidized with OsO4 and N-methylmorpholine-N-oxide to the epoxy diol (VI). Reaction of (VI) with camphorsulfonic acid in wet CH2Cl2 gave the corresponding tetraol, which on exposure to p-anisaldehyde dimethyl acetal (VII) produced selectively the acetal (VIII). The reduction of the ester group of (VIII) with LiAlH4, followed by silylation with TBDPSi-Cl afforded the monosilylated derivative (IX). The reaction of (IX) with SOCl2 in the presence of pyridine generated the cyclic sulfite ester (X), which was oxidized to sulfate (XI) using RuCl3 and NaIO4.

1 Winkler, J.D.; Lewin, N.E.; Blumberg, P.M.; Harrison, S.; Kim, S.; Synthesis and biological evaluation of highly functionalized analogues of ingenol. J Am Chem Soc 1999, 121, 2, 296.
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) 30276 methyl (1S,4S,5S,9R)-4-[(methoxycarbonyl)oxy]-14-oxotricyclo[7.4.1.0(1,5)]tetradecane-7-carboxylate C18H26O6 详情 详情
(II) 30277 methyl (1S,4S,5S,9R)-6-bromo-4-[(methoxycarbonyl)oxy]-14-oxotricyclo[7.4.1.0(1,5)]tetradecane-7-carboxylate C18H25BrO6 详情 详情
(III) 30278 methyl (1S,4S,5S,9R)-4-hydroxy-14-oxotricyclo[7.4.1.0(1,5)]tetradec-6-ene-7-carboxylate C16H22O4 详情 详情
(IV) 30279 methyl (1S,9R)-14-oxotricyclo[7.4.1.0(1,5)]tetradeca-4,6-diene-7-carboxylate C16H20O3 详情 详情
(V) 30280 methyl (1S,4S,6R,10R)-15-oxo-5-oxatetracyclo[8.4.1.0(1,6).0(4,6)]pentadec-7-ene-8-carboxylate C16H20O4 详情 详情
(VI) 30281 methyl (1S,4S,6S,7R,8R,10R)-7,8-dihydroxy-15-oxo-5-oxatetracyclo[8.4.1.0(1,6).0(4,6)]pentadecane-8-carboxylate C16H22O6 详情 详情
(VIII) 30282 methyl (1S,6R,8R,9S,11R,13R,16S)-8,16-dihydroxy-11-(4-methoxyphenyl)-17-oxo-10,12-dioxatetracyclo[7.6.1.1(1,6).0(13,16)]heptadecane-8-carboxylate C24H30O8 详情 详情
(IX) 30283 (1S,6R,8S,9R,11S,13R,16S)-8-([[tert-butyl(diphenyl)silyl]oxy]methyl)-8,16-dihydroxy-11-(4-methoxyphenyl)-10,12-dioxatetracyclo[7.6.1.1(1,6).0(13,16)]heptadecan-17-one C39H48O7Si 详情 详情
(X) 30284 (1S,4R,6R,8S,9S,13S,15R)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-6-(4-methoxyphenyl)-5,7,10,12-tetraoxa-11lambda(4)-thiapentacyclo[13.4.1.0(1,9).0(4,9).0(8,13)]icosane-11,20-dione C39H46O8SSi 详情 详情
(XI) 30285 (1S,4R,6R,8S,9S,13S,15R)-13-([[tert-butyl(diphenyl)silyl]oxy]methyl)-6-(4-methoxyphenyl)-5,7,10,12-tetraoxa-11lambda(6)-thiapentacyclo[13.4.1.0(1,9).0(4,9).0(8,13)]icosane-11,11,20-trione C39H46O9SSi 详情 详情
Extended Information