A facile synthesis of 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one as a deuterium labeled synthon for (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide.
A facile synthesis of 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one as a deuterium labeled synthon for (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide.
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轻松合成 5,5-二氘代-4-二甲基（苯基）甲硅烷基-6-十一烷基-四氢吡喃-2-酮，作为 (-)-四氢利普他汀和 (+)-δ-十六内酯的氘标记合成。
DOI：
10.1002/jlcr.3081
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发表时间：
2013
影响因子：
1.8
通讯作者：
S. Ghosh
中科院分区：
文献类型：
--
作者：
S. Wagh;Raghunath Chowdhury;S. Mukhopadhyay;S. Ghosh
氘标记的生物活性化合物正变得越来越重要，因为它们可以用作示踪剂或替代化合物，以了解作用机制，吸收，分布，代谢和排泄。氘化药物分子（重质药物）由于其与氢类似物相比具有更好的稳定性和生物利用度而变得新颖和流行。因此，用氘在特定位置标记有机分子越来越受欢迎。在这项工作中，我们利用(S)- n -（2-吡咯烷基甲基）吡咯烷/三氟乙酸/ D2 O组合催化的高收率和高同位素纯度的高区域选择性和对映选择性的甲基-d3烷基酮直接Michael加成到二甲基（苯基）硅基亚丙酸二甲酯。以甲基-d3十一烷基酮和二甲基（苯基）硅基亚丙酸二甲酯为原料，经硅控制的非对映选择性酮还原、内酯化和去氧羰基化反应合成了5,5-二氘-4-二甲基（苯基）硅基-6-十一烷基-四氢吡喃-2-酮。双氘化硅基化四氢吡喃-2- 1是双(2)H2标记的(+)-4-羟基-6-十一烷基四氢吡喃-2- 1的前体，是合成双氘(-)-四氢lipstatin和(+)-δ-十六烷内酯的高级中间体。
Deuterium-labeled biologically active compounds are gaining importance because they can be utilized as tracers or surrogate compounds to understand the mechanism of action, absorption, distribution, metabolism, and excretion. Deuterated drug molecules (heavy drugs) become novel as well as popular because of better stability and bioavailability compared with their hydrogen analogs. Labeling of organic molecules with deuterium at specific positions is thus gaining popularity. In this work, we have exploited a highly regioselective and enantioselective direct Michael addition of methyl-d3 alkyl ketones to dimethyl(phenyl)silylmethylene malonate that was catalyzed by (S)-N-(2-pyrrolidinylmethyl)pyrrolidine/trifluoroacetic acid/ D2 O combination with high yield and isotopic purity. The 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one was obtained from the adduct of methyl-d3 undecanyl ketone and dimethyl(phenyl)silylmethylene malonate by a silicon controlled diastereoselective ketone reduction, lactonization, and deethoxycarbonylation. The dideuterated silylated tetrahydropyran-2-one is the precursor for geminal (2) H2 -labeled (+)-4-hydroxy-6-undecyl-tetrahydropyran-2-one, an advanced intermediate for gem-dideutero (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide syntheses.
影响因子：
5.2
作者：
Betancort, JM;Barbas, CF
通讯作者：
Barbas, CF
影响因子：
3.9
作者：
Bertelsen, KM;Venkatakrishnan, K;Greenblatt, DJ
通讯作者：
Greenblatt, DJ