2-(trimethylsilyl)ethyl (2E,4E,6S)-6-[(2R,5S,7R,8S)-7-((2E,4E,6S,7S)-6,8-bis[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-2,4-octadienyl)-2-butyl-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-6-hydroxy-3-methyl-2,4-hexadienoate -Drug Synthesis Database

【结构式】

【分子编号】41559

【品名】2-(trimethylsilyl)ethyl (2E,4E,6S)-6-[(2R,5S,7R,8S)-7-((2E,4E,6S,7S)-6,8-bis[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-2,4-octadienyl)-2-butyl-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-6-hydroxy-3-methyl-2,4-hexadienoate

【CA登记号】n/a

【分子式】C₄₇H₈₈O₇Si₃

【分子量】849.46802

【元素组成】C 66.46% H 10.44% O 13.18% Si 9.92%

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：(XXVI)

A new Wittig condensation of aldehyde (XV) with phosphorane (XVI) in refluxing benzene gives the diunsaturated ester (XVII), which is reduced with DIBAL to the corresponding alcohol, and oxidated with DMP yielding the aldehyde (XVIII). The condensation of (XVIII) with the chiral propionyloxazolidinethione (XIX) by means of Sn(OTf)2 and 1-ethylpiperidine in dichloromethane affords the adduct (XX), which is treated with NaBH4 in THF to eliminate the chiral auxiliary and afford diol (XXI). The metalation of (XXI) with Bu3SnH and a Pd catalyst gives the vinylstannane (XXII), which is desilylated with TBAF in THF yielding the trihydroxycompound (XXIII). The condensation of stannane (XXIII) with iodobutenoic ester (XXIV) by means of a Pd catalyst affords the diunsaturated ester (XXV), which is selectively disilylated with TBDMSCl and imidazole in hot DMF to provide the disilyl ether (XXVI).

参考文献中间体

合成目标

【1】 Guzzupe, A.N.; et al.; Total synthesis of the epidermal growth factor inhibitor (-)-reveromycin B. J Org Chem 2001, 66, 7, 2382.
【2】 Cuzzupe, A.N.; et al.; Total synthesis of (-)-reveromycin B. Org Lett 2000, 2, 2, 191.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	41549	(E)-4-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2-methyl-2-butenal	n/a	C₂₇H₄₆O₄Si	详情	详情
(XVI)	14689	Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate	2605-67-6	C₂₁H₁₉O₂P	详情	详情
(XVII)	41550	methyl (2E,4E)-6-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-4-methyl-2,4-hexadienoate	n/a	C₃₀H₅₀O₅Si	详情	详情
(XVIII)	41551	(2E,4E)-6-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-4-methyl-2,4-hexadienal		C₂₉H₄₈O₄Si	详情	详情
(XIX)	41552	1-[(4S)-4-isopropyl-2-thioxo-1,3-oxazolidin-3-yl]-1-propanone		C₉H₁₅NO₂S	详情	详情
(XX)	41553	(2R,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-3-hydroxy-1-[(4S)-4-isopropyl-2-thioxo-1,3-oxazolidin-3-yl]-2,6-dimethyl-4,6-octadien-1-one		C₃₈H₆₃NO₆SSi	详情	详情
(XXI)	41554	(2S,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2,6-dimethyl-4,6-octadiene-1,3-diol		C₃₂H₅₆O₅Si	详情	详情
(XXII)	41555	(2S,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-[(1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-(tributylstannyl)-2-propenyl]-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2,6-dimethyl-4,6-octadiene-1,3-diol	n/a	C₄₄H₈₄O₅SiSn	详情	详情
(XXIII)	41556	(2S,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-[(1S,2E)-1-hydroxy-3-(tributylstannyl)-2-propenyl]-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2,6-dimethyl-4,6-octadiene-1,3-diol	n/a	C₃₈H₇₀O₅Sn	详情	详情
(XXIV)	41557	2-(trimethylsilyl)ethyl (E)-3-iodo-2-butenoate	n/a	C₉H₁₇IO₂Si	详情	详情
(XXV)	41558	2-(trimethylsilyl)ethyl (2E,4E,6S)-6-[(2R,5S,7R,8S)-2-butyl-7-[(2E,4E,6S,7S)-6,8-dihydroxy-3,7-dimethyl-2,4-octadienyl]-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-6-hydroxy-3-methyl-2,4-hexadienoate	n/a	C₃₅H₆₀O₇Si	详情	详情
(XXVI)	41559	2-(trimethylsilyl)ethyl (2E,4E,6S)-6-[(2R,5S,7R,8S)-7-((2E,4E,6S,7S)-6,8-bis[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-2,4-octadienyl)-2-butyl-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-6-hydroxy-3-methyl-2,4-hexadienoate	n/a	C₄₇H₈₈O₇Si₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVI)

The esterification of the secondary OH group of (XXVI) with acid (XXVII) by means of DCC and DMAP gives the corresponding ester (XXVIII), which is selectively desilylated with HF/pyridine in THF giving the primary alcohol (XXIX). The oxidation of (XXIX) with DMP in pyridine/THF yields the corresponding aldehyde (XXX), which by a new Wittig condensation with phosphorane (XXXI) in dichloromethane affords the fully silylated precursor (XXXII). Finally this compound is desilylated by a treatment with TBAF in DMF.

参考文献中间体

合成目标

【1】 Guzzupe, A.N.; et al.; Total synthesis of the epidermal growth factor inhibitor (-)-reveromycin B. J Org Chem 2001, 66, 7, 2382.
【2】 Cuzzupe, A.N.; et al.; Total synthesis of (-)-reveromycin B. Org Lett 2000, 2, 2, 191.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXVI)	41559	2-(trimethylsilyl)ethyl (2E,4E,6S)-6-[(2R,5S,7R,8S)-7-((2E,4E,6S,7S)-6,8-bis[[tert-butyl(dimethyl)silyl]oxy]-3,7-dimethyl-2,4-octadienyl)-2-butyl-8-methyl-1,6-dioxaspiro[4.5]dec-2-yl]-6-hydroxy-3-methyl-2,4-hexadienoate	n/a	C₄₇H₈₈O₇Si₃	详情	详情
(XXVII)	41560	4-oxo-4-[2-(trimethylsilyl)ethoxy]butyric acid		C₉H₁₈O₄Si	详情	详情
(XXVIII)	41561			C₅₆H₁₀₄O₁₀Si₄	详情	详情
(XXIX)	41562			C₅₀H₉₀O₁₀Si₃	详情	详情
(XXX)	41563		n/a	C₅₀H₈₈O₁₀Si₃	详情	详情
(XXXI)	41564	2-(trimethylsilyl)ethyl 2-(triphenylphosphoranylidene)acetate		C₂₅H₂₉O₂PSi	详情	详情
(XXXII)	41565		n/a	C₅₇H₁₀₂O₁₁Si₄	详情	详情

Extended Information