methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4S)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-yl]-5-iodopentanoate -Drug Synthesis Database

【结构式】

【分子编号】37114

【品名】methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4S)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-yl]-5-iodopentanoate

【CA登记号】

【分子式】C₂₆H₄₁IO₇

【分子量】592.51181

【元素组成】C 52.71% H 6.97% I 21.42% O 18.9%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(IIIa)

16-Methylprostaglandin PGF2alpha methyl ester (Ia-b) is cyclized with iodine/sodium bicarbonate to give (IIa-b), which is acetylated with acetic anhydride/pyridine to (IIIa-b). Dehydrohalogenation with DBN generates the protected PGI2 analogue (IVa-b), which reacts smoothly with chlorosulfonyl isocyanate (A) to afford the adduct (Va-b). Without isolation (Va-b) gives on treatment with triethylamine in acetonitrile or solvolysis with N,N-dimethylformamide (DMF) the stable protected 5-cyano analoque (VIa-b), which contains up to ca. 5% Z-isomer, readily removed by chromatography. Finally, saponification affords the free ZK-34,798 (nileprost).

参考文献中间体

合成目标

【1】 Lohaus, G.; Nitrilsynthesen mit chlorsulfonylisocyanat. Chem Ber 1967, 100, 2719-29.
【2】 Vorbruggen, H.; Reaktive isocyanate I. Sie direkte einfuehrung von nitrilgruppen in ungesattigte systeme. Eine einfache umwandlung von carbosauren in ihre nitrile. Tetrahedron Lett 1968, 1631-34.
【3】 Tanouchi, T.; Miyake, H.; Igushi, Y.; Hayashi, M.; Iguchi, S.; The synthesis of 16(R)- or 16(S)-methylprostaglandins. J Org Chem 1973, 38, 1250-51.
【4】 Whittaker, N.; A synthesis of prostaglandin sodium salt. Tetrahedron Lett 1977, 2805-08.
【5】 Vorbruggen, H.; Skuballa, W.; Raduchel, B.; Losert, W.; Loge, P.; Muller, B.; Mannesmann, G. (Schering AG); 5-Cyano-prostacyclin derivs.. US 4219479 .
【6】 Hashimoto, S.; Nileprost. Drugs Fut 1982, 7, 9, 643.

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)	14101	Chlorosulfonyl isocyanate	1189-71-5	CClNO₃S	详情	详情
(Ia)	37110	methyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R,4S)-3-hydroxy-4-methyloctyl]cyclopentyl]-5-heptenoate		C₂₂H₄₀O₅	详情	详情
(Ib)	37111	methyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R,4R)-3-hydroxy-4-methyloctyl]cyclopentyl]-5-heptenoate		C₂₂H₄₀O₅	详情	详情
(IIa)	37112	methyl 5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S,4S)-3-hydroxy-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-yl]-5-iodopentanoate		C₂₂H₃₇IO₅	详情	详情
(IIb)	37113	methyl 5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S,4R)-3-hydroxy-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-yl]-5-iodopentanoate		C₂₂H₃₇IO₅	详情	详情
(IIIa)	37114	methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4S)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-yl]-5-iodopentanoate		C₂₆H₄₁IO₇	详情	详情
(IIIb)	37115	methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4R)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-yl]-5-iodopentanoate		C₂₆H₄₁IO₇	详情	详情
(IVa)	37116	methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4S)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoate		C₂₆H₄₀O₇	详情	详情
(IVb)	37117	methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4R)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoate		C₂₆H₄₀O₇	详情	详情
(Va)	37118	methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4S)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-ylidene]-6-[(chlorosulfonyl)amino]-6-oxohexanoate		C₂₇H₄₀ClNO₁₀S	详情	详情
(Vb)	37119	methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4R)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-ylidene]-6-[(chlorosulfonyl)amino]-6-oxohexanoate		C₂₇H₄₀ClNO₁₀S	详情	详情
(VIa)	37120	methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4S)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-ylidene]-5-cyanopentanoate		C₂₇H₃₉NO₇	详情	详情
(VIb)	37121	methyl 5-[(3aR,4R,5R,6aS)-5-(acetoxy)-4-[(E,3S,4R)-3-(acetoxy)-4-methyl-1-octenyl]hexahydro-2H-cyclopenta[b]furan-2-ylidene]-5-cyanopentanoate		C₂₇H₃₉NO₇	详情	详情

Extended Information