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【结 构 式】 
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【分子编号】29321 【品名】(4R)-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]-2-cyclopenten-1-one 【CA登记号】 |
【 分 子 式 】C20H36O2Si2 【 分 子 量 】364.67564 【元素组成】C 65.87% H 9.95% O 8.77% Si 15.4% |
合成路线1
该中间体在本合成路线中的序号：(IX)The reaction of 4-hydroxy-1-octyne (I) with chlorotrimethylsilane and imidazole in DMF gives 4-trimethylsilyloxy-1-octyne (II), which is converted to 1-iodo-4-trimethylsilyloxy-trans-1-octene (III) by reaction with bis(3-methyl-2-butyl)borane, trimethylamine oxide, NaOH and finally I2. The hydrolysis of (III) with acetic acid in THF affords 1-iodo-4-hydroxy-trans-1-octene (IV), which is oxidized with pyridinium chlorochromate in methylene chloride yielding 1-iodo-4-oxo-trans-1-octene (V). The Grignard condensation of (V) with vinylmagnesium bromide in THF gives 4 hydroxy-4-vinyl-1-iodo-trans-1-octene (VI), which is protected with trimethylsilyl chloride as before yielding 4-trimethylsilyloxy-4-vinyl-1-iodo-trans-1-octene (VII). The reaction of (VII) with tert-butyllithium in ether and then with copper(I)-1-pentyne-tributylphosphine in HMPT affords the copper salt (VIII), which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trimethylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X). Finally, this compound is hydrolyzed with acetic acid in THF water.
| 【1】 Middlenton, B.F.; Martin, J.W.; Grudzinskas, C.V.; Chen, S.L. (American Cyanamid Co.); Novel prostaglandin compounds. ES 475787; FR 2410648; GB 2009173; US 4198521 . |
| 【2】 Middlenton, B.F.; Martin, J.W.; Grudzinskas, C.V.; Chen, S.L. (American Cyanamid Co.); Nouveaux acides 15-désoxy-16-hydroprotanoïques 16-substitués doués d'activité pharmaceutiques et leur procédé de préparation. DE 2813342; ES 468353; FR 2385696; JP 7939047; US 4131737 . |
| 【3】 Pfenning, J.; et al. (American Cyanamid Co.); 15-Deoxy-16-substituted protanoic acids. DE 2837530; ES 472908; FR 2401899; GB 2006186; JP 54046748; JP 7946748 . |
| 【4】 Adaikan, P.G.; Serradell, M.N.; Castaner, J.; DHV-PGE2. Drugs Fut 1985, 10, 5, 382. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 16524 | bromo(vinyl)magnesium | 1826-67-1 | C2H3BrMg | 详情 | 详情 |
| (B) | 29319 | 1-Pentynyl copper salt tri(tert-butyl)phosphine complex | C17H34CuP | 详情 | 详情 | |
| (I) | 29312 | 1-octyn-4-ol | C8H14O | 详情 | 详情 | |
| (II) | 29313 | (2-butyl-4-pentynyl)(trimethyl)silane | C12H24Si | 详情 | 详情 | |
| (III) | 29314 | [(E)-2-butyl-5-iodo-4-pentenyl](trimethyl)silane | C12H25ISi | 详情 | 详情 | |
| (IV) | 29315 | (E)-1-iodo-1-octen-4-ol | C8H15IO | 详情 | 详情 | |
| (V) | 29316 | (E)-1-iodo-1-octen-4-one | C8H13IO | 详情 | 详情 | |
| (VI) | 29317 | (5E)-3-butyl-6-iodo-1,5-hexadien-3-ol | C10H17IO | 详情 | 详情 | |
| (VII) | 29318 | [(E)-2-butyl-5-iodo-2-vinyl-4-pentenyl](trimethyl)silane | C14H27ISi | 详情 | 详情 | |
| (VIII) | 29320 | [(1E)-4-butyl-4-[(trimethylsilyl)methyl]-1,5-hexadienyl](1-pentynyl)copper | C19H34CuSi | 详情 | 详情 | |
| (IX) | 29321 | (4R)-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]-2-cyclopenten-1-one | C20H36O2Si2 | 详情 | 详情 | |
| (X) | 29322 | (2R,3R,4R)-3-[(1E)-4-butyl-4-[(trimethylsilyl)methyl]-1,5-hexadienyl]-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]cyclopentanone | C34H64O2Si3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The oxidation of 1-hepten-3-ol (XI) with pyridinium chlorochromate gives 1-hepten-3-one (XIII), which by a Grignard condensation with propargylmagnesium bromide (XIII) is converted to 4-hydroxy-4-vinyl-1-octyne (XIV). The protection of (XIV) with trimethylsilyl chloride and imidazole as before yields 4-trimethylsilyloxy-4-vinyl-1-octyne (XV), which by reaction with tri-n-butylstannane and azobisisobutyronitrile at 125 C affords 1-(tri-n-butylstannyl)-4-vinyl-4-(trimethylsilyloxy)-1-octene (XVI). Finally, this compound, by reaction with butyllithium and copper(I)-1-pentyne tributylphosphine as before yields the copper salt (VIII), which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trime-thylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X). Finally, this compound is hydrolyzed with acetic acid in THF water.
| 【1】 Grudzinkas, C.V.; Bimbaum, J.E.; Chen. S.L.; Chan, P.S.; Floyd, M.B.; Weiss, M.J.; Cervoni, P.; Prostaglandins and congeners. 29. (16RS)-Rac-15-deoxy-16-hydroxy-16-vivyl-protaglandin E2, an orally and transdermally active hypotensive agent of prolonged duration. J Med Chem 1982, 25, 5, 492-494. |
| 【2】 Adaikan, P.G.; Serradell, M.N.; Castaner, J.; DHV-PGE2. Drugs Fut 1985, 10, 5, 382. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 29319 | 1-Pentynyl copper salt tri(tert-butyl)phosphine complex | C17H34CuP | 详情 | 详情 | |
| (VIII) | 29320 | [(1E)-4-butyl-4-[(trimethylsilyl)methyl]-1,5-hexadienyl](1-pentynyl)copper | C19H34CuSi | 详情 | 详情 | |
| (IX) | 29321 | (4R)-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]-2-cyclopenten-1-one | C20H36O2Si2 | 详情 | 详情 | |
| (X) | 29322 | (2R,3R,4R)-3-[(1E)-4-butyl-4-[(trimethylsilyl)methyl]-1,5-hexadienyl]-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]cyclopentanone | C34H64O2Si3 | 详情 | 详情 | |
| (XI) | 29323 | 1-hexen-3-ol | 4798-44-1 | C6H12O | 详情 | 详情 |
| (XII) | 29324 | 1-hexen-3-one | 1629-60-3 | C6H10O | 详情 | 详情 |
| (XIII) | 29064 | bromo(2-propynyl)magnesium | C3H3BrMg | 详情 | 详情 | |
| (XIV) | 29325 | 3-butyl-1-hexen-5-yn-3-ol | C10H16O | 详情 | 详情 | |
| (XV) | 29326 | (2-butyl-2-vinyl-4-pentynyl)(trimethyl)silane | C14H26Si | 详情 | 详情 | |
| (XVI) | 29327 | [(E)-2-butyl-5-(tributylstannyl)-2-vinyl-4-pentenyl](trimethyl)silane | C26H54SiSn | 详情 | 详情 |