【结 构 式】 |
【分子编号】37956 【品名】(1S)-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl (3S,6R,7S,8S)-3-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8-tetramethyl-5-oxo-12-tridecenoate 【CA登记号】 |
【 分 子 式 】C30H53IO5Si 【 分 子 量 】648.73779 【元素组成】C 55.54% H 8.23% I 19.56% O 12.33% Si 4.33% |
合成路线1
该中间体在本合成路线中的序号:(XI)Asymmetric allylation of 3-iodomethacrolein (VII) with (+)-allyldiisopinocampheyl borane at -100 C provided the enantiopure alcohol (IX). Subsequent coupling of (IX) with the diastereomeric mixture of (6R,7S) and (6S,7R)-acids (X) using DCC and DMAP afforded a mixture of diastereomeric esters from which the required (6R,7S)-isomer (XI) was isolated by flash chromatography. Ring closure by means of olefin methatesis in the presence of a ruthenium initiator gave a separable mixture of E (XII) and Z (XIII) macrolactones. Subsequent desilylation of the desired Z isomer (XIII) with HF.Pyr in THF provided the macrocyclic diol (XIV). Introduction of the thiazole unit in (XIV) was carried out by Stille coupling of vinyl iodide (XIV) with thiazolyl stannane (VI) in the presence of Pd catalyst to provide (XV). Finally, epoxidation of (XV) with methylperoxycarboximidic acid, generated in situ from hydrogen peroxide and acetonitrile, furnished the title compound.
【1】 Nicolaou, K.C.; et al.; Total synthesis of epothilone E and analogs with modified side chains through the Stille coupling reaction. Angew Chem. Int Ed Engl 1998, 37, 1-2, 84. |
【2】 Nicolaou, K.C.; et al.; Total synthesis of epothilone E and related side-chain modified analogues via a stille coupling based strategy. Bioorg Med Chem 1999, 7, 5, 665. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VI) | 37951 | [4-(tributylstannyl)-1,3-thiazol-2-yl]methanol | C16H31NOSSn | 详情 | 详情 | |
(VII) | 37952 | (E)-3-iodo-2-methyl-2-propenal | C4H5IO | 详情 | 详情 | |
(VIII) | 37953 | allyl[(1S,2R,3S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl][(5S,6S)-4,4,6-trimethylbicyclo[3.1.1]hept-1-yl]borane | C23H39B | 详情 | 详情 | |
(IX) | 37954 | (1E,3S)-1-iodo-2-methyl-1,5-hexadien-3-ol | C7H11IO | 详情 | 详情 | |
(X) | 37955 | (3S,8S)-3-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid | C23H44O5Si | 详情 | 详情 | |
(XI) | 37956 | (1S)-1-[(E)-2-iodo-1-methylethenyl]-3-butenyl (3S,6R,7S,8S)-3-[[tert-butyl(dimethyl)silyl]oxy]-7-hydroxy-4,4,6,8-tetramethyl-5-oxo-12-tridecenoate | C30H53IO5Si | 详情 | 详情 | |
(XII) | 37957 | (4S,7R,8S,9S,16S)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-hydroxy-16-[(E)-2-iodo-1-methylethenyl]-5,5,7,9-tetramethyloxa-13-cyclohexadecene-2,6-dione | C28H49IO5Si | 详情 | 详情 | |
(XIII) | 37958 | (4S,7R,8S,9S,16S)-4-[[tert-butyl(dimethyl)silyl]oxy]-8-hydroxy-16-[(E)-2-iodo-1-methylethenyl]-5,5,7,9-tetramethyloxa-13-cyclohexadecene-2,6-dione | C28H49IO5Si | 详情 | 详情 | |
(XIV) | 37959 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-16-[(E)-2-iodo-1-methylethenyl]-5,5,7,9-tetramethyloxa-13-cyclohexadecene-2,6-dione | C22H35IO5 | 详情 | 详情 | |
(XV) | 37960 | (4S,7R,8S,9S,16S)-4,8-dihydroxy-16-[(E)-2-[2-(hydroxymethyl)-1,3-thiazol-4-yl]-1-methylethenyl]-5,5,7,9-tetramethyloxa-13-cyclohexadecene-2,6-dione | C26H39NO6S | 详情 | 详情 |