(4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methox -Drug Synthesis Database

【结构式】

【分子编号】42445

【品名】(4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methox

【CA登记号】

【分子式】C₇₃H₁₀₃ClIO₁₀PSi₂

【分子量】1390.116752

【元素组成】C 63.07% H 7.47% Cl 2.55% I 9.13% O 11.51% P 2.23% Si 4.04%

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：(LXXXV)

Synthesis of intermediate (LXXXV): The condensation of aldehyde intermediate (LXXX) with iododihydropyran (LXIII) by means of n-BuLi in ethyl ether gives the adduct (LXXXI), which is methoxylated with NIS, HC(OMe)3, Bu3SnH and AIBN, yielding the intermediate (LXXXII). Desilylation of (LXXXII) with TBAF and resilylation with TBDMSCl and imidazole to afford silylated (LXXXIII) now switch the Tips groups of (LXXXII) to the more labile Tbdms groups. The selective desilylation of the primary Tbdms group of (LXXXIII) with HF in pyridine/methanol gives the butanol derivative (LXXXIV), which is treated successively with Ts2O, NaI and finally with PPh3 and DIEA in hot acetonitrile/methanol to yield the desired phosphonium iodide intermediate (LXXXV).

参考文献中间体

合成目标

【1】 Hayward, M.M.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 2. Angew Chem. Int Ed Engl 1998, 37, 1-2, 192.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(LXIII)	42424	(4-[(2R,3S,4R)-6-iodo-3-methyl-4-[(triisopropylsilyl)oxy]-3,4-dihydro-2H-pyran-2-yl]butoxy)(triisopropyl)silane; (2R,3S,4R)-6-iodo-3-methyl-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-dihydro-2H-pyran-4-yl triisopropylsilyl ether	C₂₈H₅₇IO₃Si₂	详情	详情
(LXXX)	42440	(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-carbaldehyde	C₄₁H₅₉ClO₇Si	详情	详情
(LXXXI)	42441	(S)-[(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]((2R,3S,4R)-3-methyl-4-[(triisopropylsilyl)oxy]-2-[4-[(triisopropylsilyl)oxy]butyl]-3,4-d	C₆₉H₁₁₇ClO₁₀Si₃	详情	详情
(LXXXII)	42442	(S)-[(2R,3R,4R,5S,6R)-6-[(4S,5E)-7-chloro-2-methylene-4-[(triisopropylsilyl)oxy]-5,7-octadienyl]-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl]((2R,4S,5S,6R)-2-methoxy-5-methyl-4-[(triisopropylsilyl)oxy]-6-[4-[(triisopropylsilyl)oxy	C₇₀H₁₂₁ClO₁₁Si₃	详情	详情
(LXXXIII)	42443	(S)-[(2R,4S,5S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-(4-[[tert-butyl(dimethyl)silyl]oxy]butyl)-2-methoxy-5-methyltetrahydro-2H-pyran-2-yl][(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis	C₆₁H₁₀₃ClO₁₁Si₃	详情	详情
(LXXXIV)	42444	4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methoxy	C₅₅H₈₉ClO₁₁Si₂	详情	详情
(LXXXV)	42445	(4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methox	C₇₃H₁₀₃ClIO₁₀PSi₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(LXXXV)

Synthesis of the target 213774: The Wittig condensation of the intermediate aldehyde (L) with the intermediate phosphonium iodide (LXXXV) by means of LDA in THF/HMPA gives the adduct (LXXXVI). Cleavage of the Mpm protecting groups and simultaneous hydrolysis of the methyl ketal group with DDQ, followed by KF-induced elimination of the silyl ester protecting group and macrolactonization under Yamaguchi conditions, afforded macrolactone (LXXXVII). Finally, this compound is desilylated with HF/pyridine in THF.

参考文献中间体

合成目标

【1】 Hayward, M.M.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 2. Angew Chem. Int Ed Engl 1998, 37, 1-2, 192.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(L)	42411	tert-butyl(diphenyl)silyl 2-[(2R,4S,6R,8S,10S)-4-(acetoxy)-8-(2-[(1R,2S,3S)-2-(acetoxy)-5-[(2S,4S,6S,8R)-8-formyl-4-methoxy-1,7-dioxaspiro[5.5]undec-2-yl]-1,3-dimethyl-4-oxopentyl]-2-propenyl)-10-hydroxy-10-methyl-1,7-dioxaspiro[5.5]undec-2-yl]a	C₅₃H₇₄O₁₄Si	详情	详情
(LXXXV)	42445	(4-[(2R,3S,4S,6R)-4-[[tert-butyl(dimethyl)silyl]oxy]-6-[(S)-[(2R,3R,4R,5S,6R)-6-((4S,5E)-4-[[tert-butyl(dimethyl)silyl]oxy]-7-chloro-2-methylene-5,7-octadienyl)-4,5-bis[(4-methoxybenzyl)oxy]-3-methyltetrahydro-2H-pyran-2-yl](hydroxy)methyl]-6-methox	C₇₃H₁₀₃ClIO₁₀PSi₂	详情	详情
(LXXXVI)	42446		C₁₁₄H₁₇₅ClO₂₄Si₄	详情	详情
(LXXXVII)	42447		C₈₁H₁₃₇ClO₂₁Si₃	详情	详情

Extended Information