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【结 构 式】 
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【分子编号】52423 【品名】methyl 3-(trimethylsilyl)-4-pentenoate 【CA登记号】 |
【 分 子 式 】C9H18O2Si 【 分 子 量 】186.32622 【元素组成】C 58.02% H 9.74% O 17.17% Si 15.07% |
合成路线1
该中间体在本合成路线中的序号：(LV)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：(LIX)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 |