(8S,10R,13S,14S)-10,13-dimethyl-17-[2-(phenylsulfinyl)ethenylidene]-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one -Drug Synthesis Database

【结构式】

【分子编号】56598

【品名】(8S,10R,13S,14S)-10,13-dimethyl-17-[2-(phenylsulfinyl)ethenylidene]-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one

【CA登记号】

【分子式】C₂₇H₃₀O₂S

【分子量】418.6

【元素组成】C 77.47% H 7.22% O 7.64% S 7.66%

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：(VI)

Reaction of 9a-hydroxyandrost-4-ene-3,17-dione (I) with benzenesulfinyl chloride and pyridine gives the corresponding sulfinate (II), which by treatment with TsOH in refluxing chloroform yields androsta-4,9(11)-diene-3,17-dione (III). Reaction of the androstadienedione (III) with acetylene by means of potassium tert-butoxide in THF affords the 17a-ethynyl derivative (IV), which is treated with phenylsulfenyl chloride and TEA at 70 C to provide the sulfenate ester (V). Rearrange-ment of sulfenate (V) by warming at 40 C gives the allene sulfoxide (VI), which is treated with sodium methoxide in methanol at 25 C to yield the enol ether sulfoxide (VII). Then, by refluxing in methanol, an equilibrium between sulfoxide (VII) and sulfenate (VIII) occurs. Reaction of the non-isolated sulfenate (VIII) with the thiophile trimethyl phosphite affords the 17a-hydroxy enol ether (IX), which is finally converted to anecortave acetate by either treatment with peracetic acid and NaHCO3 in dichloromethane or bromination with Br2 and pyridine in dichloromethane to give compound (X) followed by treatment with KOAc, KI and AcOH in refluxing acetone.

参考文献中间体

合成目标

【1】 Van Rheenen, V.; Shephard, K.P.; New synthesis of cortico steroids from 17-keto steroids: Application and stereochemical study of the unsaturated sulfoxide-sulfenate rearrangement. J Org Chem 1979, 44, 9, 1582.
【2】 Castaner, J.; Sorbera, L.A.; Leeson, P.A.; Bayes, M.; Anecortave Acetate. Drugs Fut 2002, 27, 11, 1039.
【3】 Shephard, K.P.; Van Rheenen, V.H. (Pharmacia Corp.); Process for the preparation of 17alpha-hydroxyprogesterones and corticoids from androstenes. US 4041055 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	23634	acetylene	74-86-2	C₂H₂	详情	详情
(I)	28065	(8S,9R,10S,13S,14S)-9-hydroxy-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione		C₁₉H₂₆O₃	详情	详情
(II)	56594	(8S,10S,13S,14S)-10,13-dimethyl-3,17-dioxo-1,2,3,6,7,8,10,11,12,13,14,15,16,17-tetradecahydro-9H-cyclopenta[a]phenanthren-9-yl benzenesulfinate		C₂₅H₃₀O₄S	详情	详情
(III)	56595	(8S,10R,13S,14S)-10,13-dimethyl-7,8,10,12,13,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione		C₁₉H₂₄O₂	详情	详情
(IV)	56596	(8S,10R,13S,14S,17R)-17-ethynyl-17-hydroxy-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₁H₂₆O₂	详情	详情
(V)	56597	(8S,10R,13S,14S,17R)-17-ethynyl-10,13-dimethyl-3-oxo-2,3,6,7,8,10,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl benzenesulfenate		C₂₇H₃₀O₂S	详情	详情
(VI)	56598	(8S,10R,13S,14S)-10,13-dimethyl-17-[2-(phenylsulfinyl)ethenylidene]-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₇H₃₀O₂S	详情	详情
(VII)	56599	(8S,10R,13S,14S)-17-[(E)-1-methoxy-2-(phenylsulfinyl)ethylidene]-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₈H₃₄O₃S	详情	详情
(VIII)	56600	(8S,10R,13S,14S,17R)-17-(1-methoxyvinyl)-10,13-dimethyl-3-oxo-2,3,6,7,8,10,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl benzenesulfenate		C₂₈H₃₄O₃S	详情	详情
(IX)	56601	(8S,10R,13S,14S,17R)-17-hydroxy-17-(1-methoxyvinyl)-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₂H₃₀O₃	详情	详情
(X)	56602	(8S,10R,13S,14S,17R)-17-(2-bromoacetyl)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₁H₂₇BrO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Reaction of 17a-ethynyl-9,11-didehydrotestosterone (IV) with phenylsulfinyl chloride and TEA in dichloromethane gives 21-(phenylsulfinyl)pregna-4,9(11),17(20),20-tetraen-3-one (VI), which is treated with phenol and NaOH in refluxing toluene to provide 20-(phenoxy)-21-(phenylsulfinyl)pregna-4,9(11),20-trien-3-one (XXXIV). The reaction of compound (XXXIV) with trimethyl phosphite and TEA in hot methanol affords 17a-hydroxy-20-(phenoxy)pregna-4,9(11),20-trien-3-one (XXXV), which is finally treated with Oxone and KOH in hot dichloromethane, and then acetylated with Ac2O, TEA and DMAP in THF/water.

参考文献中间体

合成目标

【1】 Castaner, J.; Sorbera, L.A.; Leeson, P.A.; Bayes, M.; Anecortave Acetate. Drugs Fut 2002, 27, 11, 1039.
【2】 Sacks, C.E. (Pharmacia Corp.); Process and intermediates for the preparation of 17alpha-hydroxyprogesterones and corticoids from an enol steroid. EP 0186948 .
【3】 Shephard, K.P.; Van Rheenen, V.H. (Pharmacia Corp.); Process for the preparation of steroids. CH 630394 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	56596	(8S,10R,13S,14S,17R)-17-ethynyl-17-hydroxy-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	C₂₁H₂₆O₂	详情	详情
(VI)	56598	(8S,10R,13S,14S)-10,13-dimethyl-17-[2-(phenylsulfinyl)ethenylidene]-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	C₂₇H₃₀O₂S	详情	详情
(XXXIV)	56623	(8S,10R,13S,14S)-10,13-dimethyl-17-[(Z)-1-phenoxy-2-(phenylsulfinyl)ethylidene]-7,8,10,12,13,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-3(2H,6H)-one	C₃₃H₃₆O₃S	详情	详情
(XXXV)	56624	(8S,10R,13S,14S,17R)-17-hydroxy-10,13-dimethyl-17-(1-phenoxyvinyl)-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	C₂₇H₃₂O₃	详情	详情

Extended Information