methyl 4,4-bis(phenylsulfonyl)butanoate -Drug Synthesis Database

【结构式】

【分子编号】13819

【品名】methyl 4,4-bis(phenylsulfonyl)butanoate

【CA登记号】

【分子式】C₁₇H₁₈O₆S₂

【分子量】382.45832

【元素组成】C 53.39% H 4.74% O 25.1% S 16.77%

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：(XCV)

11) The alkylation of the exocyclic methylene double bond of the fully protected bicyclic triol (XCIV) with 4,4-bis(phenylsulfonyl)butyric acid methyl ester (XCV) by means of NaH and catalyzed by a palladium complex gives (XCVI), which is desulfonated by treatment with magnesium in dry methanol to yield the bisilylated clinprost (XCIII). Finally, this compound is desilylated with TBAF as usual.

参考文献中间体

合成目标

【1】 Graul, A.; Leeson, P.; Castaner, J.; Clinprost. Drugs Fut 1997, 22, 6, 608.
【2】 Hari, A.; Tanaka, T.; Okamura, N.; Sakauchi, K. (Teijin Ltd.); Isocarbacyclin derivs. and their preparation. JP 1988303962 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XCIII)	13817	methyl 5-[(3aS,5R,6S,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]pentanoate	C₃₄H₆₄O₄Si₂	详情	详情
(XCIV)	13818	(1R,3aS,4S,5R,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-2-methyleneoctahydro-1-pentalenyl acetate	C₃₁H₅₈O₄Si₂	详情	详情
(XCV)	13819	methyl 4,4-bis(phenylsulfonyl)butanoate	C₁₇H₁₈O₆S₂	详情	详情
(XCVI)	13820	methyl 5-[(3aS,5R,6S,6aS)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]-4,4-bis(phenylsulfonyl)pentanoate	C₄₆H₇₂O₈S₂Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XCV)

13) The synthesis of the 17,18-ditritiated clinprost can be performed as follows: The reduction of the bicyclic aldehyde (LIII) described in Scheme 4 with NaBH4 in methanol gives the hydroxymethyl derivative (CXIII), which is esterified with methyl chloroformate yielding the carbonate ester (CXIV). The condensation of (CXIV) with 4,4-bis(phenylsulfonyl)butyric acid methyl ester (XCV) catalyzed by a palladium complex in THF affords the expected alkylation product (CXV), which is treated with Mg in methanol to eliminate the phenylsulfonyl groups, giving the unsaturated pentanoic acid methyl ester derivative (XLV) already obtained in Scheme 3. The desilylation of (XLV) with TBAF followed by oxidation with SO3/Pyr yields the aldehyde (XLVI), also reported in Scheme 3. The reaction of (XLVI) with dimethyl 2-oxo-4(Z)-heptenylphosphate (CXVI) by means of NaH in THF affords the expected condensation product (CXVII), which is regioselectively reduced with LiAlH4 in THF in the presence of (S)-(-)-binaphthol to give the (Z)-17,18-didehydro-11-O-tetrahydropyranylclinprost (CXVIII). Elimination of the THP group of (CXVIII) with acetic acid in THF/water yields the (Z)-17,18-didehydroclinprost (CXIX), which is finally tritiated by hydrogenation with tritium gas in benzene/cyclohexane using tris(triphenylphosphine)rhodium(I) chloride as catalyst. 14) If the final reduction of (CXIX) is performed with hydrogen gas in benzene/cyclohexane containing cyclododecene and in the presence of a Pd/C catalyst, clinprost is obtained.

参考文献中间体

合成目标

【1】 Graul, A.; Leeson, P.; Castaner, J.; Clinprost. Drugs Fut 1997, 22, 6, 608.
【2】 Manabe, K.; Tanaka, T.; Kurozumi, S.; Kato, Y.; Syntheses of di-tritiated 9(O)-methane-DELTA6(9alpha)-prostaglandin I1 methyl esters. J Label Compd Radiopharm 1991, 29, 10, 1107-19.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(CXIII)	13838	[(3aS,5R,6R,6aS)-6-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]methanol	C₂₂H₄₀O₄Si	详情	详情
(CXIV)	13839	[(3aS,5R,6R,6aS)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]methyl methyl carbonate	C₂₄H₄₂O₆Si	详情	详情
(CXV)	13841	methyl 5-[(3aS,5R,6R,6aS)-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]-4,4-bis(phenylsulfonyl)pentanoate	C₃₉H₅₆O₉S₂Si	详情	详情
(CXVI)	13842	dimethyl (Z)-2-oxo-4-heptenylphosphonate	C₉H₁₇O₄P	详情	详情
(CXVII)	13843	methyl 5-[(3aS,5R,6S,6aS)-6-[(1E,5Z)-3-oxo-1,5-octadienyl]-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]pentanoate	C₂₈H₄₂O₅	详情	详情
(CXVIII)	13844	methyl 5-[(3aS,5R,6S,6aS)-6-[(1E,3S,5Z)-3-hydroxy-1,5-octadienyl]-5-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]pentanoate	C₂₈H₄₄O₅	详情	详情
(CXIX)	13845	methyl 5-[(3aS,5R,6S,6aS)-5-hydroxy-6-[(1E,3S,5Z)-3-hydroxy-1,5-octadienyl]-1,3a,4,5,6,6a-hexahydro-2-pentalenyl]pentanoate	C₂₂H₃₄O₄	详情	详情
(XCV)	13819	methyl 4,4-bis(phenylsulfonyl)butanoate	C₁₇H₁₈O₆S₂	详情	详情

Extended Information