　 -Drug Synthesis Database

【结构式】

【分子编号】39443

【品名】　

【CA登记号】

【分子式】C₇₉H₁₃₂O₁₅Si₄

【分子量】1434.25008

【元素组成】C 66.16% H 9.28% O 16.73% Si 7.83%

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：(LIII)

Fragment coupling: Coupling of the C10-C16 fragment (XXVIII) with the C17-C27 fragment (XLIII) by means of BuLi, Ac2O and Mg in THF gives (XLVII), which is selectively deprotected with TBAF yielding the carbinol (XLVIII). The reaction of (XLVIII) with triflic anhydride and lutidine in CH2Cl2 affords the triflate (IL), which is coupled with the C1-C9 fragment (XVIII) by means of n-BuLi in THF giving the tricyclic intermediate (L). The opening of the lactol ring of (L) with triethylsilyl chloride and imidazole yields the silylated hydroxyketone (LI), which is treated first with tert-butoxycarbonyl anhydride and then with the lithium salt of benzyl alcohol in order to convert the phenylcarboxamide of (LI) into the benzyl ester (LII). The epoxidation of the dihydropyran double bond of (LII) with MCPBA followed by epoxide opening with MeOH and oxidation of the resulting alcohol with DMP in CH2Cl2 gives the oxoketal (LIII).

参考文献中间体

合成目标

【1】 Lautens, M.; Prunet, J.A.; Carreira, E.M.; Carter, P.H.; Charette, A.B.; Evans, D.A.; Total synthesis of bryostatin 2. J Am Chem Soc 1999, 121, 33, 7540.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	40733	lithium phenylmethanolate	C₇H₇LiO	详情	详情
(IL)	39439	[(2S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(E)-3-((2S)-2-[(2R,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]butyl]-3,4-dihydro-2H-pyran-6-yl)-3-methyl-1-butenyl]tetrahydro-2H-pyran-2-yl]methyl trifluoromethanesulfonate	C₄₁H₆₉F₃O₉SSi₂	详情	详情
(XXVIII)	39419	(2R,4R,6S)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-([[tert-butyl(dimethyl)silyl]oxy]methyl)tetrahydro-2H-pyran-2-carbaldehyde	C₁₉H₄₀O₄Si₂	详情	详情
(XLIII)	39433	tert-butyl([(1R,2R)-1-([(2S)-6-[1,1-dimethyl-2-(phenylsulfonyl)ethyl]-3,4-dihydro-2H-pyran-2-yl]methyl)-2-[(4-methoxybenzyl)oxy]propyl]oxy)dimethylsilane; 2-((2S)-2-[(2R,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]butyl]-3,4-dihydro-2H-pyran-6-yl)-2-methylpropyl phenyl sulfone	C₃₃H₅₀O₆SSi	详情	详情
(XLVII)	39437	tert-butyl(dimethyl)silyl [(2S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(E)-3-((2S)-2-[(2R,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]butyl]-3,4-dihydro-2H-pyran-6-yl)-3-methyl-1-butenyl]tetrahydro-2H-pyran-2-yl]methyl ether; tert-butyl([(2S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(E)-3-((2S)-2-[(2R,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]butyl]-3,4-dihydro-2H-pyran-6-yl)-3-methyl-1-butenyl]tetrahydro-2H-pyran-2-yl]methoxy)dimethylsilane	C₄₆H₈₄O₇Si₃	详情	详情
(XLVIII)	39438	[(2S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(E)-3-((2S)-2-[(2R,3R)-2-[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]butyl]-3,4-dihydro-2H-pyran-6-yl)-3-methyl-1-butenyl]tetrahydro-2H-pyran-2-yl]methanol	C₄₀H₇₀O₇Si₂	详情	详情
(L)	39440		C₇₁H₁₁₅NO₁₂Si₃	详情	详情
(LI)	39441		C₇₇H₁₂₉NO₁₂Si₄	详情	详情
(LII)	39442		C₇₈H₁₃₀O₁₃Si₄	详情	详情
(LIII)	39443		C₇₉H₁₃₂O₁₅Si₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(LIII)

The reaction of (LIII) with HF in pyridine/methanol gives the desilylated tricyclic intermediate (LIV), which is resilylated with TESCl and DMAP in dichloromethane and debenzylated by reaction with 1,4-cyclohexadiene over Pd/C to afford the free hydroxyacid (LV). The cyclization of (LV) by means of 2,4,6-trichlorobenzoyl chloride, i-PrNEt2 and DMAP gives the macrocycle (LVI), which is selectively deprotected with PPTS in methanol/HC(OEt)3/dichloromethane, and oxidized with Dess Martin periodinane (DMP) in pyridine/dichloromethane yielding the diketone (LVII). The reaction of (LVII) with the Fuji's chiral phosphonate (LVIII) by means of NaHMDS in THF affords the C13 enoate (LIX), which is condensed with methyl glyoxylate by means of KHMDS in THF to give the C21 enoate (LX). The stereoselective reduction of the carbonyl group of (LX) with BH3/SMe2 catalyzed by the oxazaborolidine (A), followed by esterification with methoxyacetic anhydride provides the methoxyacetate (LXI).

参考文献中间体

合成目标

【1】 Lautens, M.; Prunet, J.A.; Carreira, E.M.; Carter, P.H.; Charette, A.B.; Evans, D.A.; Total synthesis of bryostatin 2. J Am Chem Soc 1999, 121, 33, 7540.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40732	methyl 2-oxoacetate	922-68-9	C₃H₄O₃	详情	详情
(A)	39460	1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole		C₁₈H₂₀BNO	详情	详情
(LIII)	39443			C₇₉H₁₃₂O₁₅Si₄	详情	详情
(LIV)	39444			C₅₆H₇₈O₁₅	详情	详情
(LV)	39445			C₆₁H₁₀₀O₁₅Si₂	详情	详情
(LVI)	39446			C₆₁H₉₈O₁₄Si₂	详情	详情
(LVII)	39447	(1S,3S,7R,11S,15S,17R,21R,23S,25S)-1,11-dimethoxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-10,10,26,26-tetramethyl-21-[(triethylsilyl)oxy]-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-ene-5,12,19-trione		C₅₅H₈₂O₁₄Si	详情	详情
(LVIII)	39448	methyl 2-(2-oxo-2lambda(5)-dinaphtho[2,1-d:1,2-f][1,3,2]dioxaphosphepin-2-yl)acetate		C₂₃H₁₇O₅P	详情	详情
(LIX)	39449	methyl 2-[(1S,3S,7R,11S,15S,17R,21R,23S,25S)-1,11-dimethoxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-10,10,26,26-tetramethyl-12,19-dioxo-21-[(triethylsilyl)oxy]-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate		C₅₈H₈₆O₁₅Si	详情	详情
(LX)	39450	methyl 2-[(1S,3S,7R,11S,15S,17R,21R,23S,25S)-1,11-dimethoxy-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-13-[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-12,19-dioxo-21-[(triethylsilyl)oxy]-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate		C₆₁H₈₈O₁₇Si	详情	详情
(LXI)	39451	methyl 2-[(1S,3S,7R,11S,12S,15S,17R,21R,23S,25S)-1,11-dimethoxy-12-[(2-methoxyacetyl)oxy]-25-[(4-methoxybenzyl)oxy]-17-[(1R)-1-[(4-methoxybenzyl)oxy]ethyl]-13-[(E)-2-methoxy-2-oxoethylidene]-10,10,26,26-tetramethyl-19-oxo-21-[(triethylsilyl)oxy]-18,27,28,29-tetraoxatetracyclo[21.3.1.1(3,7).1(11,15)]nonacos-8-en-5-ylidene]acetate		C₆₄H₉₄O₁₉Si	详情	详情

Extended Information