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【结 构 式】

【分子编号】52413

【品名】 

【CA登记号】

【 分 子 式 】C20H32O6

【 分 子 量 】368.47048

【元素组成】C 65.19% H 8.75% O 26.05%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(LIII)

The previously referenced vinyl iodide intermediate (XXXIV) was obtained as follows: The reaction of L-mannonic acid gamma-lactone (XLVIII) with cyclohexanone (XLIX) by means of H2SO4 in toluene gave the bis-cyclohexylidene ketal (L), which was reduced with DIBAL in dichloromethane to yield the lactol (LI). The condensation of (LI) with the phosphonium chloride (LII) by means of t-Bu-OK in refluxing THF afforded the vinyl ether (LIII), which was hydroxylated with OsO4 and dihydroquinidine-4-chlorobenzoate as chiral ligand and acylated with acetic anhydride and pyridine to provide the diacetate (LIV). The condensation of (LIV) with the functionalized allyl silane (LV) by means of BF3/Et2O in acetonitrile gave the adduct (LVI), which was submitted to cyclization by means of Triton B(OMe) in THF/methyl acetate to yield the perhydropyrano[3,2-b]pyran derivative (LVII). The selective hydrolysis of the exocyclic cyclohexylidene ketal of (LVII) with hot AcOH/water afforded the diol (LVIII), which by oxidative cleavage with NaIO4 in THF afforded the aldehyde (LIX). The coupling of (LIX) with the silylated vinyl iodide (LX), catalyzed by NiCl2 and CrCl2 in DMSO, gave the silylated allyl alcohol (LXI), which was submitted to cleavage of the cyclohexylidene ketal by means of AcOH/TFA to yield the trihydroxy compound (LXII). The protection of the three OH groups of (LXII) with Tbdms-OTf and lutidine in dichloromethane afforded the tris-Tbdms protected vinyl silane (LXIII), which was finally iodinated with N-iodosuccinimide (NIS) in acetonitrile/chloroacetonitrile to provide the target vinyl iodide intermediate (XXXIV).

1 Kishi, Y.; Stamos, D.P.; Synthetic studies on halichondrins: A practical synthesis of the C.1-C.13 segment. Tetrahedron Lett 1996, 37, 48, 8643.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXXIV) 48420 methyl 2-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-6-((1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-iodo-2-propenyl)octahydropyrano[3,2-b]pyran-2-yl]acetate C32H63IO7Si3 详情 详情
(XLVIII) 25665 (3R,4S,5S)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxydihydro-2(3H)-furanone C6H10O6 详情 详情
(XLIX) 11059 Cyclohexanone 108-94-1 C6H10O 详情 详情
(L) 52411   C18H26O6 详情 详情
(LI) 52412   C18H28O6 详情 详情
(LII) 39163 (methoxymethyl)(triphenyl)phosphonium chloride 4009-98-7 C20H20ClOP 详情 详情
(LIII) 52413   C20H32O6 详情 详情
(LIV) 52414   C23H34O9 详情 详情
(LV) 52423 methyl 3-(trimethylsilyl)-4-pentenoate C9H18O2Si 详情 详情
(LVI) 52415   C27H40O9 详情 详情
(LVII) 52416   C25H38O8 详情 详情
(LVIII) 52417   C19H30O8 详情 详情
(LIX) 52418   C18H26O7 详情 详情
(LX) 52419 (2-iodoethenyl)(trimethyl)silane C5H11ISi 详情 详情
(LXI) 52420   C23H38O7Si 详情 详情
(LXII) 52421 methyl 2-{(2R,4aS,6S,7S,8R,8aR)-7,8-dihydroxy-6-[(E)-1-hydroxy-3-(trimethylsilyl)-2-propenyl]octahydropyrano[3,2-b]pyran-2-yl}acetate C17H30O7Si 详情 详情
(LXIII) 52422 methyl 2-{(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tert-butyl(dimethyl)silyl]oxy}-6-[(1S,2E)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-(trimethylsilyl)-2-propenyl]octahydropyrano[3,2-b]pyran-2-yl}acetate C35H72O7Si4 详情 详情

合成路线2

该中间体在本合成路线中的序号:(LVI)

The previously referenced vinyl iodide intermediate (XXXIV) was obtained as follows: The reaction of L-mannonic acid gamma-lactone (LI) with cyclohexanone (LII) by means of H2SO4 in toluene gave the bis-cyclohexylidene ketal (LIII), which was reduced with DIBAL in dichloromethane to yield the lactol (LIV). The condensation of (LIV) with the phosphonium chloride (LV) by means of t-Bu-OK in refluxing THF afforded the vinyl ether (LVI), which was hydroxylated with OsO4 and dihydroquinidine-4-chlorobenzoate as chiral ligand and acylated with acetic anhydride and pyridine to provide the diacetate (LVII). The condensation of (LVII) with the functionalized allyl silane (LVIII) by means of BF3/Et2O in acetonitrile gave the adduct (LIX), which was submitted to cyclization by means of Triton B(OMe) in THF/methyl acetate to yield the perhydropyrano[3,2-b]pyran derivative (LX). The selective hydrolysis of the exocyclic cyclohexylidene ketal of (LX) with hot HOAc/water afforded the diol (LXI), which by oxidative cleavage with NaIO4 in THF afforded the aldehyde (LXII). The coupling of (LXII) with the silylated vinyl iodide (LXIII), catalyzed by NiCl2 and CrCl2 in DMSO, gave the silylated allyl alcohol (LXIV), which was submitted to cleavage of the cyclohexylidene ketal by means of HOAc/TFA to yield the trihydroxy compound (LXV). The protection of the three OH groups of (LXV) with Tbdms-OTf and lutidine in dichloromethane afforded the tris-Tbdms protected vinyl silane (LXVI), which was finally iodinated with N-iodosuccinimide (NIS) in acetonitrile/chloroacetonitrile to provide the target vinyl iodide intermediate (XXXIV).

1 Kishi, Y.; Stamos, D.P.; Synthetic studies on halichondrins: A practical synthesis of the C.1-C.13 segment. Tetrahedron Lett 1996, 37, 48, 8643.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXXIV) 48420 methyl 2-[(2R,4aS,6S,7R,8S,8aS)-7,8-bis[[tert-butyl(dimethyl)silyl]oxy]-6-((1S,2E)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-iodo-2-propenyl)octahydropyrano[3,2-b]pyran-2-yl]acetate C32H63IO7Si3 详情 详情
(LI) 25665 (3R,4S,5S)-5-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxydihydro-2(3H)-furanone C6H10O6 详情 详情
(LII) 11059 Cyclohexanone 108-94-1 C6H10O 详情 详情
(LIII) 52411   C18H26O6 详情 详情
(LIV) 52412   C18H28O6 详情 详情
(LV) 39163 (methoxymethyl)(triphenyl)phosphonium chloride 4009-98-7 C20H20ClOP 详情 详情
(LVI) 52413   C20H32O6 详情 详情
(LVII) 52414   C23H34O9 详情 详情
(LVIII) 52415   C27H40O9 详情 详情
(LIX) 52423 methyl 3-(trimethylsilyl)-4-pentenoate C9H18O2Si 详情 详情
(LX) 52416   C25H38O8 详情 详情
(LXI) 52417   C19H30O8 详情 详情
(LXII) 52418   C18H26O7 详情 详情
(LXIII) 52419 (2-iodoethenyl)(trimethyl)silane C5H11ISi 详情 详情
(LXIV) 52420   C23H38O7Si 详情 详情
(LXV) 52421 methyl 2-{(2R,4aS,6S,7S,8R,8aR)-7,8-dihydroxy-6-[(E)-1-hydroxy-3-(trimethylsilyl)-2-propenyl]octahydropyrano[3,2-b]pyran-2-yl}acetate C17H30O7Si 详情 详情
(LXVI) 52422 methyl 2-{(2R,4aS,6S,7R,8S,8aS)-7,8-bis{[tert-butyl(dimethyl)silyl]oxy}-6-[(1S,2E)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-(trimethylsilyl)-2-propenyl]octahydropyrano[3,2-b]pyran-2-yl}acetate C35H72O7Si4 详情 详情
Extended Information