(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-17-glycoloyl-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one -Drug Synthesis Database

【结构式】

【分子编号】40461

【品名】(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-17-glycoloyl-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one

【CA登记号】

【分子式】C₂₂H₂₉FO₅

【分子量】392.4676632

【元素组成】C 67.33% H 7.45% F 4.84% O 20.38%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

By reaction of dexamethasone alcohol (I) with methanesulfonyl chloride giving dexamethasone mesylate (II), which is the transesterified with potassium linoleate in dimethylformamide.

参考文献中间体

合成目标

【1】 Castaner, J.; Arrigoni-Martelli, E.; Dexamethasone-21-linoleate. Drugs Fut 1976, 1, 7, 316.
【2】 Szporny, L.; Pifferi, G.; Pinza, M.; 21-Ester von ungesattigten Fettsaureestern des Desa- und Betamethazons. BE 0764130; DE 2113163; FR 2112302; GB 1292785 .
【3】 Pifferi, G.; et al.; New unsaturated esters for tropical antiphlogistic use; Synthesis and spectroscopic properties od dexamethasone-21-linoleate. Arzneim-Forsch Drug Res 1976, 26, 1, 7.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	40461	(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-17-glycoloyl-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	C₂₂H₂₉FO₅	详情	详情
(II)	40462	(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-17-(2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]acetyl)-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	C₂₅H₃₅FO₅S	详情	详情
(III)	40463	potassium (9Z,12Z)-9,12-octadecadienoate	C₁₈H₃₁KO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Esterification of the primary hydroxyl group of dexamethasone (I) by treatment with 4-nitrophenyl chloroformate (II) in the presence of N-methylmorpholine afforded the nitrophenyl carbonate (III). Condensation of the active ester (III) with mono-N-Boc-1,6-diaminohexane (IV) produced carbamate (V). After acidic deprotection of the Boc group, the resultant amine (VI) was acylated with succinimidyl 4-maleimidobutyrate (VII), yielding the title amide.

参考文献中间体

合成目标

【1】 Bernasconi, A.; et al.; Synthesis of a dexamethasone-21-maleimido-linked derivative as a potential molecule for specific gene delivery. Tetrahedron Lett 2001, 42, 37, 6511.

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)	40461	(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-17-glycoloyl-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₂H₂₉FO₅	详情	详情
(II)	16605	4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene	7693-46-1	C₇H₄ClNO₄	详情	详情
(III)	50240	2-[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl 4-nitrophenyl carbonate		C₂₉H₃₂FNO₉	详情	详情
(IV)	31638	tert-butyl 6-aminohexylcarbamate	51857-17-1	C₁₁H₂₄N₂O₂	详情	详情
(V)	50241	2-[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl 6-[(tert-butoxycarbonyl)amino]hexylcarbamate		C₃₄H₅₁FN₂O₈	详情	详情
(VI)	50242	2-[(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl 6-aminohexylcarbamate		C₂₉H₄₃FN₂O₆	详情	详情
(VII)	50243	4-Maleimidobutyric acid N-hydroxysuccinimide ester; Maleimidobutyric acid N-hydroxysuccinimide ester; N-(4-Maleimidobutyryloxy)succinimide; N-(gamma-Maleimidobutyryloxy)succinimide; N-Succinimidyl 4-Maleimidobutyrate	80307-12-6	C₁₂H₁₂N₂O₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Treatment of dexamethasone (I) with trimethyl orthocyclopropanecarboxylate (II) in the presence of p-toluenesulfonic acid gives the mixed orthoester (III), which, upon acidic hydrolysis with oxalic acid leads to the C-17 cyclopropanecarboxylate ester (IV). Subsequent esterification of (IV) with cyclohexanecarbonyl chloride (V) furnishes the desired dexamethasone diester.

参考文献中间体

合成目标

【1】 Komoto, T.; Okawa, J.; Ogawa, Y.; Sato, S.; Taido, N.; Kuraishi, T. (SSP Co., Ltd.); Novel steroid derivs.. EP 0393658; JP 1990279694; US 5063222 .

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)	40461	(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-17-glycoloyl-11,17-dihydroxy-10,13,16-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₂H₂₉FO₅	详情	详情
(II)	63235	1-(trimethoxymethyl)cyclopropane; cyclopropyl(dimethoxy)methyl methyl ether		C₇H₁₄O₃	详情	详情
(III)	63236			C₂₇H₃₅FO₆	详情	详情
(IV)	63237	(8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-17-glycoloyl-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl cyclopropanecarboxylate		C₂₆H₃₃FO₆	详情	详情
(V)	17220	cyclohexanecarbonyl chloride; Cyclohexanecarboxylic acid chloride	2719-27-9	C₇H₁₁ClO	详情	详情

Extended Information