錝,5″S)-2-{3′-Methoxy-2′-propoxy-5′-[5″-(3,4,5-trimethoxyphenyl)tetrahydrofuran-2″-yl] phenylsulfonyl}ethanol(MK-287) which was potent PAF antagonist, was enantioselectively synthesized in eight steps by a...錝,5″S)-2-{3′-Methoxy-2′-propoxy-5′-[5″-(3,4,5-trimethoxyphenyl)tetrahydrofuran-2″-yl] phenylsulfonyl}ethanol(MK-287) which was potent PAF antagonist, was enantioselectively synthesized in eight steps by addition, oxidation, hot decomposition, hydrogenation and so on from (-)-4,10-dioxatricyclo-[5.2.1.0 2,6]-decene-3-ole(1). Asymmetry was introduced using the nucleophilic addition of the triisopropoxytitanium to the lactol 1. The second asymmetric center was installed by a highly stereocontrolled acid-assisted reduction with sodium cyanoborohydride of the hemiketal formed. The product MK-287 was optically pure.展开更多
A series of aromatic cyanohydrins and their O silyl ethers have been synthesized by trimethylsilylcyanation of aromatic aldehydes using a catalyst generated in situ from optically active R (+) 1,1 2 bisnaphthol with...A series of aromatic cyanohydrins and their O silyl ethers have been synthesized by trimethylsilylcyanation of aromatic aldehydes using a catalyst generated in situ from optically active R (+) 1,1 2 bisnaphthol with n butyl lithium. Mandelonitrile was prepared in an isolated yield 70% with more than \{e.e.\} =60%. The effect of solvents and the amount of catalyst on enantioselectivity was also investigated.展开更多
为有效提高医药中间体对映纯1,3-氧杂硫杂环戊烷(P_(R))的产率,本研究对动态动力学拆分,制备P_(R),并建立其动力学模型。采用一锅法合成对映纯((R)-5乙酰氧基-1,3-氧杂噻喃-2-基)乙基苯甲酸酯(P_(R)),其中,催化剂为固定化丝孢酵母脂肪酶...为有效提高医药中间体对映纯1,3-氧杂硫杂环戊烷(P_(R))的产率,本研究对动态动力学拆分,制备P_(R),并建立其动力学模型。采用一锅法合成对映纯((R)-5乙酰氧基-1,3-氧杂噻喃-2-基)乙基苯甲酸酯(P_(R)),其中,催化剂为固定化丝孢酵母脂肪酶(Trichosporonlaibachii CBS 5791),底物为2-(苯基甲氧基)乙醛(A),1,4-二硫-2,5-二醇(B)和乙酸苯酯(D)。研究结果表明,其转化率可以达到99.6%,产率为97.3%,对映体过量百分率(enantiomeric excess,ee%)为96.5%,所建立的反应体系动力学模型,很好地拟合了实验数据,表明可逆半硫代乙缩醛转化反应动力学遵从幂律方程,而酶催化内酯化反应为带产物抑制的序列机制。该研究可高效合成P_(R),最大限度地提高了生产效率。展开更多
文摘錝,5″S)-2-{3′-Methoxy-2′-propoxy-5′-[5″-(3,4,5-trimethoxyphenyl)tetrahydrofuran-2″-yl] phenylsulfonyl}ethanol(MK-287) which was potent PAF antagonist, was enantioselectively synthesized in eight steps by addition, oxidation, hot decomposition, hydrogenation and so on from (-)-4,10-dioxatricyclo-[5.2.1.0 2,6]-decene-3-ole(1). Asymmetry was introduced using the nucleophilic addition of the triisopropoxytitanium to the lactol 1. The second asymmetric center was installed by a highly stereocontrolled acid-assisted reduction with sodium cyanoborohydride of the hemiketal formed. The product MK-287 was optically pure.
文摘A series of aromatic cyanohydrins and their O silyl ethers have been synthesized by trimethylsilylcyanation of aromatic aldehydes using a catalyst generated in situ from optically active R (+) 1,1 2 bisnaphthol with n butyl lithium. Mandelonitrile was prepared in an isolated yield 70% with more than \{e.e.\} =60%. The effect of solvents and the amount of catalyst on enantioselectivity was also investigated.
文摘为有效提高医药中间体对映纯1,3-氧杂硫杂环戊烷(P_(R))的产率,本研究对动态动力学拆分,制备P_(R),并建立其动力学模型。采用一锅法合成对映纯((R)-5乙酰氧基-1,3-氧杂噻喃-2-基)乙基苯甲酸酯(P_(R)),其中,催化剂为固定化丝孢酵母脂肪酶(Trichosporonlaibachii CBS 5791),底物为2-(苯基甲氧基)乙醛(A),1,4-二硫-2,5-二醇(B)和乙酸苯酯(D)。研究结果表明,其转化率可以达到99.6%,产率为97.3%,对映体过量百分率(enantiomeric excess,ee%)为96.5%,所建立的反应体系动力学模型,很好地拟合了实验数据,表明可逆半硫代乙缩醛转化反应动力学遵从幂律方程,而酶催化内酯化反应为带产物抑制的序列机制。该研究可高效合成P_(R),最大限度地提高了生产效率。
