【结 构 式】 |
【分子编号】11110 【品名】(3S,5R)-2-Hexyl-3-hydroxy-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoic acid 【CA登记号】 |
【 分 子 式 】C27H52O5 【 分 子 量 】456.70688 【元素组成】C 71.01% H 11.48% O 17.52% |
合成路线1
该中间体在本合成路线中的序号:(LIII)Oxetanone (XLV) can also be obtained as follows: The reaction of 3(R)-hydroxytetradecanoic acid tert-butyl ester (XLVI) with DHP and p-toluenesulfonic acid gives the corresponding tetrahydropyranyl ether (XLVII), which is reduced with dibutylaluminum hydride (DIBAL) in toluene to the aldehyde (XI), already obtained. Compound (XI) is condensed with 2-(p-toluenesulfinyl)acetic acid tert-butyl ester (XLVIII) by means of tert-butylmagnesium bromide in ether-THF affording the sulfinylhydroxy ester (II), which is treated with aluminum amalgam in THF-water to yield the hydroxy ester (L). The alkylation of (L) with hexyl bromide (LI) by means of butyllithium and diisopropylamine in THF-hexane affords 2-hexyl-3(S)-hydroxy-5(R)-(tetrahydropyranyloxy)hexadecanoic acid tert-butyl ester (LII), which is hydrolyzed with KOH in methanol to the corresponding free acid (LIII). The lactonization of (LIII) with pyridinium p-toluenesulfonate in hot ethanol affords oxetanone (LIV) as a diastereomeric mixture, which is separated by column chromatography, finally yielding oxetanone (XLV), previously obtained in scheme 11082301c.
【1】 Barbier, P.; Schneider, F.; Synthesis of tetrahydrolipstatin and tetrahydroesterastin, compounds with beta-lactone moiety. Stereoselective hydrogenation of a beta-keto delta-lactone and conversion of the delta-lactone into a beta-lactone. J Org Chem 1988, 53, 6, 1218-21. |
【2】 Prous, J.; Mealy, N.; Castaner, J.; Orlistat. Drugs Fut 1994, 19, 11, 1003. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IL) | 11106 | tert-butyl (3S,5R)-3-hydroxy-2-[(4-methylphenyl)sulfinyl]-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoate | C32H54O6S | 详情 | 详情 | |
(XLV) | 11102 | (3S,4S)-3-Hexyl-4-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)tridecyl]-2-oxetanone | C27H50O4 | 详情 | 详情 | |
(XLVI) | 11103 | tert-butyl (3R)-3-hydroxytetradecanoate | C18H36O3 | 详情 | 详情 | |
(XLVII) | 11104 | tert-butyl (3R)-3-(tetrahydro-2H-pyran-2-yloxy)tetradecanoate | C23H44O4 | 详情 | 详情 | |
(XLVIII) | 11105 | tert-butyl 2-[(4-methylphenyl)sulfinyl]acetate | C13H18O3S | 详情 | 详情 | |
(L) | 11107 | tert-butyl (3S,5R)-3-hydroxy-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoate | C25H48O5 | 详情 | 详情 | |
(LI) | 11108 | n-Hexyl bromide; 1-Bromohexane | 111-25-1 | C6H13Br | 详情 | 详情 |
(LII) | 11109 | tert-butyl (3S,5R)-2-hexyl-3-hydroxy-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoate | C31H60O5 | 详情 | 详情 | |
(LIII) | 11110 | (3S,5R)-2-Hexyl-3-hydroxy-5-(tetrahydro-2H-pyran-2-yloxy)hexadecanoic acid | C27H52O5 | 详情 | 详情 | |
(LIV) | 63075 | (4S)-3-hexyl-4-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)tridecyl]-2-oxetanone | C27H50O4 | 详情 | 详情 |