3-sulfanyldihydro-2(3H)-furanone -Drug Synthesis Database

【结构式】

【分子编号】46294

【品名】3-sulfanyldihydro-2(3H)-furanone

【CA登记号】

【分子式】C₄H₆O₂S

【分子量】118.15644

【元素组成】C 40.66% H 5.12% O 27.08% S 27.14%

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：(IV)

Treatment of carboxylic acid (I) with diethyl chlorophosphate (II) in the presence of Et3N furnished the corresponding mixed anhydride (III). This was then condensed with the sodium salt of alpha-mercapto-gamma-butyrolactone (IV) to produce the title thioester.

参考文献中间体

合成目标

【1】 Biggadike, K.; Procopiou, P.A. (Glaxo Wellcome plc); Lactone derivs. of 17beta-carboxy, carbothio and amide androstane derivs.. JP 1999501675; US 6197761; WO 9724365 .

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)	47372	(4aS,4bR,5S,6aS,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-4a,6a-dimethyl-2-oxo-8-propyl-2,3,4,4a,4b,5,6,6a,9a,10,10a,10b,11,12-tetradecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxole-6b-carboxylic acid		C₂₄H₃₂F₂O₆	详情	详情
(II)	23623	Chlorophosphoric acid ethyl ester；Phosphorochloridic acid diethyl ester；Diethyl chlorophosphate;diethyl phosphorochloridate	814-49-3	C₄H₁₀ClO₃P	详情	详情
(III)	47373	[(4aS,4bR,5S,6aS,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-4a,6a-dimethyl-2-oxo-8-propyl-2,3,4,4a,4b,5,6,6a,9a,10,10a,10b,11,12-tetradecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]carbonyl diethyl phosphate		C₂₈H₄₁F₂O₉P	详情	详情
(IV)	46294	3-sulfanyldihydro-2(3H)-furanone		C₄H₆O₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Fluocinolone acetonide (I) was selectively mesylated at the primary alcohol group by means of methanesulfonyl chloride and pyridine. Treatment of the resulting mesylate (II) with alpha-mercapto-gamma-butyrolactone (IV) in the presence of NaH in THF produced the desired thioether derivative.

参考文献中间体

合成目标

【1】 Burgess, C.M.; Biggadike, K.; Angell, R.M.; et al.; Selective plasma hydrolysis of glucocorticoid gamma-lactones and cyclic carbonates by the enzyme paraoxonase: An ideal plasma inactivation mechanism. J Med Chem 2000, 43, 1, 19.
【2】 Farrell, R.M.; Biggadike, K. (Glaxo Wellcome Inc.); 21-(2-Oxo-tetrahydrofuran)-thio pregnane derivs., a process for their production and pharmaceutical compsns. containing them. US 6013244; WO 9724367 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	46292	(4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one	C₂₄H₃₀F₂O₆	详情	详情
(II)	46293	2-[(4aS,4bR,5S,6aS,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-4a,6a,8,8-tetramethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl methanesulfonate	C₂₅H₃₂F₂O₈S	详情	详情
(III)	46294	3-sulfanyldihydro-2(3H)-furanone	C₄H₆O₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Ketal exchange of acetonide (I) with butyraldehyde (II) under acidic conditions provides the corresponding butylidene ketal (III). The primary alcohol group of (III) is then mesylated with methanesulfonyl chloride in pyridine to furnish (IV). Subsequent displacement of the mesylate group of (IV) by racemic alpha-mercapto-gamma-butyrolactone (V) gives rise to a mixture of the title compound along with its (R)-epimer (VI), which can be separated employing preparative HPLC. (1,2)

参考文献中间体

合成目标

【1】 Angell, R.M.; Biggadike, K.; Farrell, R.M.; Flack, S.S.; Hancock, A.P.; Irving, W.R.; Lynn, S.M.; Procopiou, P.A.; Novel glucocorticoid antedrugs possessing a 21-(gamma-lactone) ring. J Chem Soc - Perkins Trans I 2002, 6, 831.
【2】 Farrell, R.M.; Biggadike, K. (Glaxo Wellcome Inc.); 21-(2-Oxo-tetrahydrofuran)-thio pregnane derivs., a process for their production and pharmaceutical compsns. containing them. US 6013244; WO 9724367 .

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)	47571	(4aS,4bR,5S,6aS,6bS,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-5-hydroxy-4a,6a,8,8-tetramethyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one		C₂₄H₃₂F₂O₆	详情	详情
(II)	23694	butyraldehyde	123-72-8	C₄H₈O	详情	详情
(III)	47572	(4aS,4bR,5S,6aS,6bS,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-6b-glycoloyl-5-hydroxy-4a,6a-dimethyl-8-propyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one		C₂₅H₃₄F₂O₆	详情	详情
(IV)	64290	2-[(4aS,4bR,5S,6aS,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-4a,6a-dimethyl-2-oxo-8-propyl-2,3,4,4a,4b,5,6,6a,9a,10,10a,10b,11,12-tetradecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl methanesulfonate		C₂₆H₃₆F₂O₈S	详情	详情
(V)	46294	3-sulfanyldihydro-2(3H)-furanone		C₄H₆O₂S	详情	详情
(VI)	64291	(4aS,4bR,5S,6aS,6bS,8R,9aR,10aS,10bS,12S)-4b,12-difluoro-5-hydroxy-4a,6a-dimethyl-6b-(2-{[(3R)-2-oxotetrahydro-3-furanyl]sulfanyl}acetyl)-8-propyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2		C₂₉H₃₈F₂O₇S	详情	详情

Extended Information