methyl (1S,4S,5S,9R)-4-hydroxy-14-oxotricyclo[7.4.1.0(1,5)]tetradec-6-ene-7-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】30278

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

【CA登记号】

【分子式】C₁₆H₂₂O₄

【分子量】278.34828

【元素组成】C 69.04% H 7.97% O 22.99%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

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.

参考文献中间体

合成目标

【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：(III)

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.

参考文献中间体

合成目标

【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	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