(1R,2R,6S)-1-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-hydroxy-2,6-dimethyl-7-octenyl methanesulfonate -Drug Synthesis Database

【结构式】

【分子编号】46190

【品名】(1R,2R,6S)-1-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-hydroxy-2,6-dimethyl-7-octenyl methanesulfonate

【CA登记号】

【分子式】C₂₆H₄₇NO₅S₂Si

【分子量】545.88042

【元素组成】C 57.21% H 8.68% N 2.57% O 14.65% S 11.75% Si 5.14%

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：(XXXVI)

The selective deprotection of (XXX) with CSA in dichloromethane gives the primary alcohol (XXXI), which is oxidized with DMP in dichloromethane to yield the aldehyde (XXXII). The condensation of (XXXII) with methyltriphenylphosphonium iodide (XXXIII) by means of BuLi in hexane/THF, followed by treatment with HCl in ethanol, affords the diunsaturated vicinal diol (XXXIV), which is selectively silylated to provide the vicinal diol (XXXV). The monosulfonation of (XXXV) with Ms-Cl and TEA furnishes the mesylate (XXXVI), which is cyclized to the epoxide (XXXVII) by means of K2CO3 in methanol. The oxidation of the terminal double bond of (XXXVII) with OsO4 and NaIO4 gives the aldehyde (XXXVIII), which is condensed with the intermediate ketone (XVIII) by means of LDA in THF to provide the adduct (XXXIX).

参考文献中间体

合成目标

【1】 Mulzer, J.; et al.; A novel highly stereoselective total synthesis of epothilone B and of its (12R,13R) acetonide. Tetrahedron Lett 2000, 41, 40, 7635.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXXIIII)	13484	Methyl(triphenyl)phosphonium iodide; Methyltriphenylphosphonium iodide	2065-66-9	C₁₉H₁₈IP	详情	详情
(XVIII)	44451	(5S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4,4-dimethyl-7-octen-3-one		C₁₆H₃₂O₂Si	详情	详情
(XXX)	46184	tert-butyl(dimethyl)silyl (2S)-5-[(4R,5R)-5-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methylpentyl ether; 4-[(E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4R,5R)-5-((4S)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylpentyl)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-2-methyl-1-butenyl]-2-methyl-1,3-thiazole		C₃₃H₆₃NO₄SSi₂	详情	详情
(XXXI)	46186	(2S)-5-[(4R,5R)-5-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methyl-1-pentanol		C₂₇H₄₉NO₄SSi	详情	详情
(XXXII)	46187	(2S)-5-[(4R,5R)-5-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2,2,4-trimethyl-1,3-dioxolan-4-yl]-2-methylpentanal		C₂₇H₄₇NO₄SSi	详情	详情
(XXXIV)	46188	(1E,3S,5R,6R,10S)-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,11-dodecadiene-3,5,6-triol		C₁₉H₃₁NO₃S	详情	详情
(XXXV)	46189	(1E,3S,5R,6R,10S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2,6,10-trimethyl-1-(2-methyl-1,3-thiazol-4-yl)-1,11-dodecadiene-5,6-diol		C₂₅H₄₅NO₃SSi	详情	详情
(XXXVI)	46190	(1R,2R,6S)-1-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-hydroxy-2,6-dimethyl-7-octenyl methanesulfonate		C₂₆H₄₇NO₅S₂Si	详情	详情
(XXXVII)	46191	tert-butyl(dimethyl)silyl (1S,2E)-2-methyl-1-([(2S,3R)-3-methyl-3-[(4S)-4-methyl-5-hexenyl]oxiranyl]methyl)-3-(2-methyl-1,3-thiazol-4-yl)-2-propenyl ether; 4-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methyl-4-[(2S,3R)-3-methyl-3-[(4S)-4-methyl-5-hexenyl]oxiranyl]-1-butenyl)-2-methyl-1,3-thiazole		C₂₅H₄₃NO₂SSi	详情	详情
(XXXVIII)	46192	(2S)-5-[(2R,3S)-3-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-methyloxiranyl]-2-methylpentanal		C₂₄H₄₁NO₃SSi	详情	详情
(XXXIX)	46193	(4S,7R,8S,9S)-4-[[tert-butyl(dimethyl)silyl]oxy]-12-[(2R,3S)-3-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-methyloxiranyl]-8-hydroxy-5,5,7,9-tetramethyl-1-dodecen-6-one		C₄₀H₇₃NO₅SSi₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Mono-protection of 1,4-butanediol (XI) by means of 4-methoxybenzyl chloride, followed by Swern oxidation with DMSO/SO3-Pyr, leads to the aldehyde (XII). Condensation of (XII)with the boron enolate of the N-propionyl oxazolidinone (III) and subsequent silylation with tert-butyldimethylsilyl triflate furnishes the N-acyl oxoazolidinone (XIII), which is reduced by LiBH4 to the primary alcohol (XIV), which is then subjected to Swern oxidation to produce the aldehyde (XV). Further condensation of (XV) with acyl oxazolidinone (III) leads to adduct (XVI). The free hydroxyl group of (XVI) is alkylated with chloromethyl methyl ether to produce the O-methoxymethyl derivative (XVII), which under desilylation conditions with HF-pyridine cyclizes to the lactone (XVIII).

参考文献中间体

合成目标

【1】 Choy, N.; Shin, Y.; Nguyen, P.Q.; Curran, D.P.; Balachandran, R.; Madiraju, C.; Day, B.W.; Simplified discodermolide analogues: Synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents. J Med Chem 2003, 46, 14, 2846.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(III)	25713	(4S)-4-benzyl-3-propionyl-1,3-oxazolidin-2-one	C₁₃H₁₅NO₃	详情	详情
(XI)	46190	(1R,2R,6S)-1-[(2S,3E)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-butenyl]-2-hydroxy-2,6-dimethyl-7-octenyl methanesulfonate	C₂₆H₄₇NO₅S₂Si	详情	详情
(XII)	64738	4-({[4-(methyloxy)phenyl]methyl}oxy)butanal	C₁₂H₁₆O₃	详情	详情
(XIII)	64739	3-[3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-methyl-6-({[4-(methyloxy)phenyl]methyl}oxy)hexanoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₃₁H₄₅NO₆Si	详情	详情
(XIV)	64740	3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-methyl-6-({[4-(methyloxy)phenyl]methyl}oxy)-1-hexanol	C₂₁H₃₈O₄Si	详情	详情
(XV)	64741	3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2-methyl-6-({[4-(methyloxy)phenyl]methyl}oxy)hexanal	C₂₁H₃₆O₄Si	详情	详情
(XVI)	64742		C₃₄H₅₁NO₇Si	详情	详情
(XVII)	64743	3-[5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,4-dimethyl-3-{[(methyloxy)methyl]oxy}-8-({[4-(methyloxy)phenyl]methyl}oxy)octanoyl]-4-(phenylmethyl)-1,3-oxazolidin-2-one	C₃₆H₅₅NO₈Si	详情	详情
(XVIII)	64744	3,5-dimethyl-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran-2-one	C₂₀H₃₀O₆	详情	详情

Extended Information