|
【结 构 式】 
|
【分子编号】26421 【品名】tert-butyl[(2R)oxiranylmethoxy]diphenylsilane; tert-butyl(diphenyl)silyl (2R)oxiranylmethyl ether 【CA登记号】 |
【 分 子 式 】C19H24O2Si 【 分 子 量 】312.48386 【元素组成】C 73.03% H 7.74% O 10.24% Si 8.99% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)Synthesis of intermediate (XXXIII): The silylation of epoxide (XXI) with TBDMSCl gives the silyl ether (XXII), which is condensed with 1,3-dithiane (VI) by means of n-BuLi to yield the alcohol (XXIII). Epoxidation of (XXIII) with TBAF and NaH affords the epoxide (XXIV), which is condensed with vinyl lithium and CuCN to provide the allyl alcohol (XXV). The methylation of (XXV) with MeI and NaH in THF gives the methyl ether (XXVI). The silylation of epoxide (XXI) with TBDPSCl gives the silyl ether (XXVII), which is condensed with vinyl lithium (II) by means of CuCN in THF, yielding the allyl alcohol (XXVIII). The reaction of (XXVIII) with Boc-ON, n-BuLi and IBr affords the cyclic carbonate (XXIX), which is treated with K2CO3 in MeOH and silylated with TBDPSCl to provide the protected epoxide (XXX). The condensation of epoxide (XXX) with allyl ether (XXVI) by means of NaOtBu and n-BuLi in THF furnished the adduct (XXXI), which is cyclized by means of TBAF and converted into the acetylenic tetrahydropyran (XXXII). Finally, the iodination and reprotection of (XXXII) with Bu3SnH, AIBN, NIS, Mpm-OCH2Cl and DIEA gives the desired intermediate (XXXIII).
| 【1】 Guo, J.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 1. Angew Chem. Int Ed Engl 1998, 37, 1-2, 187. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 42368 | vinyllithium | 917-57-7 | C2H3Li | 详情 | 详情 |
| (VI) | 42372 | 1,3-dithiane | 505-23-7 | C4H8S2 | 详情 | 详情 |
| (XXI) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (XXII) | 42374 | tert-butyl(dimethyl)[(2R)oxiranylmethoxy]silane; tert-butyl(dimethyl)silyl (2R)oxiranylmethyl ether | C9H20O2Si | 详情 | 详情 | |
| (XXIII) | 42387 | (2R)-1-[[tert-butyl(dimethyl)silyl]oxy]-3-(1,3-dithian-2-yl)-2-propanol | C13H28O2S2Si | 详情 | 详情 | |
| (XXIV) | 42388 | (2R)-2-(1,3-dithian-2-ylmethyl)oxirane | C7H12OS2 | 详情 | 详情 | |
| (XXV) | 42389 | (2S)-1-(1,3-dithian-2-yl)-4-penten-2-ol | C9H16OS2 | 详情 | 详情 | |
| (XXVI) | 42390 | (1S)-1-(1,3-dithian-2-ylmethyl)-3-butenyl methyl ether; 2-[(2S)-2-methoxy-4-pentenyl]-1,3-dithiane | C10H18OS2 | 详情 | 详情 | |
| (XXVII) | 26421 | tert-butyl[(2R)oxiranylmethoxy]diphenylsilane; tert-butyl(diphenyl)silyl (2R)oxiranylmethyl ether | C19H24O2Si | 详情 | 详情 | |
| (XXVIII) | 26422 | (2R)-1-[[tert-butyl(diphenyl)silyl]oxy]-4-penten-2-ol | C21H28O2Si | 详情 | 详情 | |
| (XXIX) | 42391 | (4R,6S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-6-(iodomethyl)-1,3-dioxan-2-one | C22H27IO4Si | 详情 | 详情 | |
| (XXX) | 42392 | tert-butyl(diphenyl)silyl (1R)-2-[[tert-butyl(diphenyl)silyl]oxy]-1-[(2S)oxiranylmethyl]ethyl ether; (5R)-2,2,9,9-tetramethyl-5-[(2S)oxiranylmethyl]-3,3,8,8-tetraphenyl-4,7-dioxa-3,8-disiladecane | C37H46O3Si2 | 详情 | 详情 | |
| (XXXI) | 42393 | (2S,4R)-4,5-bis[[tert-butyl(diphenyl)silyl]oxy]-1-[2-[(2S)-2-methoxy-4-pentenyl]-1,3-dithian-2-yl]-2-pentanol | C47H64O4S2Si2 | 详情 | 详情 | |
| (XXXII) | 42394 | tert-butyl(diphenyl)silyl [(2R,4S,6R)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-methoxy-6-[(2S)-2-methoxy-4-pentynyl]tetrahydro-2H-pyran-2-yl]methyl ether; tert-butyl([(2R,4S,6R)-4-[[tert-butyl(diphenyl)silyl]oxy]-6-methoxy-6-[(2S)-2-methoxy-4-pentynyl]tetrahydro-2H-pyran-2-yl]methoxy)diphenylsilane | C45H58O5Si2 | 详情 | 详情 | |
| (XXXIII) | 42395 | tert-butyl(dimethyl)silyl (2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl ether; tert-butyl[[(2R,4S,6R)-2-[(2S,4E)-5-iodo-2-methoxy-4-pentenyl]-2-methoxy-6-([[(4-methoxybenzyl)oxy]methoxy]methyl)tetrahydro-2H-pyran-4-yl]oxy]dimethylsilane | C28H47IO7Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The reaction of silylated (S)-glycidol (I) with the vinyl copper compound (II) in ethyl ether gives the monosilylated unsaturated diol (III), which is desilylated with Bu4NF in THF yielding the diol (IV). The cyclization of (IV) by means of I2 and NaHCO3 in acetonitrile affords a mixture of the cis and trans diastereomers from which the trans isomer (V) was isolated. The acylation of (V) with potassium 4-nitrobenzoate (VI) in DMSO/18-crown-6 yields the 4-nitrobenzoyl ester (VII), which is condensed with adenine (VIII) by means of DEAD and triphenylphosphine in DMF providing the 4-nitrobenzoyl percursor (IX). Finally, (IX) is debenzoylated with NaOMe in methanol.
| 【1】 Diaz, Y.; et al.; Synthesis of purine and pyrimidine isodideoxynucleosides from (S)-glycydol using iodoetherification as key step. Synthesis of (S,S)-iso-ddA. J Org Chem 1999, 64, 17, 6508. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 26421 | tert-butyl[(2R)oxiranylmethoxy]diphenylsilane; tert-butyl(diphenyl)silyl (2R)oxiranylmethyl ether | C19H24O2Si | 详情 | 详情 | |
| (III) | 26422 | (2R)-1-[[tert-butyl(diphenyl)silyl]oxy]-4-penten-2-ol | C21H28O2Si | 详情 | 详情 | |
| (IV) | 26423 | (2R)-4-pentene-1,2-diol | C5H10O2 | 详情 | 详情 | |
| (V) | 26424 | (3R,5S)-5-(iodomethyl)tetrahydro-3-furanol | C5H9IO2 | 详情 | 详情 | |
| (VI) | 26425 | potassium 4-nitrobenzoate | 15922-01-7 | C7H4KNO4 | 详情 | 详情 |
| (VII) | 26426 | [(2S,4R)-4-hydroxytetrahydro-2-furanyl]methyl 4-nitrobenzoate | C12H13NO6 | 详情 | 详情 | |
| (VIII) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (IX) | 26427 | [(2S,4S)-4-(6-amino-9H-purin-9-yl)tetrahydro-2-furanyl]methyl 4-nitrobenzoate | C17H16N6O5 | 详情 | 详情 |