(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenal -Drug Synthesis Database

【结构式】

【分子编号】63887

【品名】(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenal

【CA登记号】

【分子式】C₃₃H₃₂O₄

【分子量】492.61468

【元素组成】C 80.46% H 6.55% O 12.99%

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：(XXV)

The chiral unsaturated aldehyde intermediate (XXV) has been obtained as follows. The reaction of the chiral lactone (XVII) first with N,O-dimethylhydroxylamine and then with PmbO-(C=NH)CCl3 gives the Weinreb amide (XVIII), which is reduced with Bu2AlH to yield the butyraldehyde (XIX). The condensation of (XIX) with phosphorane (XX) affords the unsaturated ester (XXI), which is reduced with Bu2AlH to provide the unsaturated alcohol (XXII). The reaction of (XXII) with TrCl and lutidine gives the trityl ether (XXIII), which is desilylated by means of TBAF to yield the primary alcohol (XXIV). Finally, this compound is oxidized with DMP to afford the desired unsaturated aldehyde intermediate (XXV).

参考文献中间体

合成目标

【1】 Nelson, S.G.; Cheung, W.S.; Kassick, A.J.; Hilfiker, M.A.; A de novo enantioselective total synthesis of (-)-laulimalide. J Am Chem Soc 2002, 124, 46, 13654.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	63307	1,1,1-trichloro-3-(4-methoxyphenyl)-2-propanimine		C₁₀H₁₀Cl₃NO	详情	详情
(XVII)	63880	4-{[tert-butyl(diphenyl)silyl]oxy}-2-oxetanone		C₁₉H₂₂O₃Si	详情	详情
(XVIII)	63881	(3S)-4-{[tert-butyl(diphenyl)silyl]oxy}-N-methoxy-3-[(4-methoxybenzyl)oxy]-N-methylbutanamide		C₃₀H₃₉NO₅Si	详情	详情
(XIX)	63882	(3S)-4-{[tert-butyl(diphenyl)silyl]oxy}-3-[(4-methoxybenzyl)oxy]butanal		C₂₈H₃₄O₄Si	详情	详情
(XX)	14182	ethyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate; (Carbethoxymethylene)triphenylphosphorane	1099-45-2	C₂₂H₂₁O₂P	详情	详情
(XXI)	63884	ethyl (E,5S)-6-{[tert-butyl(diphenyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-2-hexenoate		C₃₂H₄₀O₅Si	详情	详情
(XXII)	63885	(E,5S)-6-{[tert-butyl(diphenyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-2-hexen-1-ol		C₃₀H₃₈O₄Si	详情	详情
(XXIII)	63883	tert-butyl(diphenyl)silyl (2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenyl ether; tert-butyl{[(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenyl]oxy}diphenylsilane		C₄₉H₅₂O₄Si	详情	详情
(XXIV)	63886	(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexen-1-ol		C₃₃H₃₄O₄	详情	详情
(XXV)	63887	(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenal		C₃₃H₃₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXV)

Synthesis of the target Laulimalide. The condensation of the tin derivative (XXVI) with the chiral isopropenyl boron derivative (XXVII) gives the secondary alcohol (XXVIII), which is alkylated with allyl bromide (XXIX) and KHMDS to yield the allyl ether (XXX). The ring closing metathesis reaction in (XXX) by means of Schrock catalyst affords the dihydropyranyl stannane (XXXI), which is treated with N-iodosuccinimide to provide the iodovinyl compound (XXXII). The reaction of (XXXII) with BuLi and MgBr2 gives the vinylmagnesium derivative (XXXIII), which is condensed with the unsaturated aldehyde intermediate (XXV) to yield the olefinic alcohol (XXXIV). The reaction of (XXXIV) with Tbdms-Cl and imidazole affords the silyl ether (XXXV), which is selectively deprotected with formic acid, and oxidated with DMP to provide the chiral unsaturated aldehyde (XXXVI).

参考文献中间体

合成目标

【1】 Nelson, S.G.; Cheung, W.S.; Kassick, A.J.; Hilfiker, M.A.; A de novo enantioselective total synthesis of (-)-laulimalide. J Am Chem Soc 2002, 124, 46, 13654.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXV)	63887	(2S,4E)-2-[(4-methoxybenzyl)oxy]-6-(trityloxy)-4-hexenal		C₃₃H₃₂O₄	详情	详情
(XXVI)	63888	(E)-3-(tributylstannyl)-2-propenal		C₁₅H₃₀OSn	详情	详情
(XXVII)	63889			C₅H₁₁B	详情	详情
(XXVIII)	63890	(1E)-5-methyl-1-(tributylstannyl)-1,5-hexadien-3-ol		C₁₉H₃₈OSn	详情	详情
(XXIX)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(XXX)	63891	[(1E)-3-(allyloxy)-5-methyl-1,5-hexadienyl](tributyl)stannane; allyl 3-methyl-1-[(E)-2-(tributylstannyl)ethenyl]-3-butenyl ether		C₂₂H₄₂OSn	详情	详情
(XXXI)	63894	tributyl{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}stannane		C₂₀H₃₈OSn	详情	详情
(XXXII)	63893	(2S)-2-[(E)-2-iodoethenyl]-4-methyl-3,6-dihydro-2H-pyran		C₈H₁₁IO	详情	详情
(XXXIII)	63892	bromo{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}magnesium		C₈H₁₁BrMgO	详情	详情
(XXXIV)	63895	(1E,3S,4S,6E)-4-[(4-methoxybenzyl)oxy]-1-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-8-(trityloxy)-1,6-octadien-3-ol		C₄₁H₄₄O₅	详情	详情
(XXXV)	63896	tert-butyl(dimethyl)silyl (1S,2S,4E)-2-[(4-methoxybenzyl)oxy]-1-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-6-(trityloxy)-4-hexenyl ether; tert-butyl{[(1S,2S,4E)-2-[(4-methoxybenzyl)oxy]-1-{(E)-2-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]ethenyl}-6-(trityloxy)-4-hexenyl]oxy}dimethylsilane		C₄₇H₅₈O₅Si	详情	详情
(XXXVI)	63897	(2E,5S,6S,7E)-6-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-8-[(2S)-4-methyl-3,6-dihydro-2H-pyran-2-yl]-2,7-octadienal		C₂₈H₄₂O₅Si	详情	详情

Extended Information