Science Institute, Chemistry Department, University of Iceland, Dunhaga 3, 107 Reykjavik, Iceland.
J Org Chem. 2022 Sep 16;87(18):12306-12314. doi: 10.1021/acs.joc.2c01515. Epub 2022 Aug 29.
The report describes the preparation and use of a double-C3 building block intended as a head group synthon in the synthesis of saturated, mono-, and polyunsaturated 1--alkyl--glycerol type methoxylated ether lipids (MELs). The resulting head piece, an enantiopure isopropylidene-protected glyceryl glycidyl ether diastereomer, was accomplished in 49% yield (max 50%) from a 1:1 diastereomeric mixture obtained from -solketal and racemic epichlorohydrin after treatment with the Jacobsen (,)-Co(III)salen catalyst for the hydrolytic kinetic resolution of terminal epoxides. The diol hydrolytic product obtained in 47% yield from the unwanted diastereomer was reconverted into epoxide with an inversion of configuration in a three-step operation involving a highly regioselective lipase. This enabled the recovery of a substantial amount of diastereopure material after a subsequent treatment with the Jacobsen catalyst to furnish the oxirane head piece in altogether 72% yield of higher than 99% diastereomeric purity. A modified synthesis of a monounsaturated 16:1 MEL confirmed the correct stereochemistry and excellent enantiopurity of the head piece and resulted in a dramatic improvement in yields, efficiency, and economy of the synthesis.
该报告描述了一种双 C3 砌块的制备和使用，该砌块拟作为合成饱和、单不饱和和多不饱和 1-烷基-甘油型甲氧基醚脂质 (MEL) 的头基合成子。所得的头基是一种对映纯异丙叉保护的甘油缩水甘油醚非对映异构体，由 -solketal 和外消旋表氯醇以 1:1 的非对映异构体混合物为原料，经 Jacobsen (,)-Co(III)salen 催化剂对末端环氧化物的水解动力学拆分得到，产率为 49%（最高 50%）。从非所需非对映异构体中以 47%的产率得到二醇水解产物，然后在涉及高度区域选择性脂肪酶的三步操作中，将其转化为环氧化物，构型反转。这使得在随后用 Jacobsen 催化剂处理后能够回收大量的非对映体纯物质，从而以高于 99%的非对映体纯度总共以 72%的产率获得环氧化合物头基。一种改良的单不饱和 16:1 MEL 的合成方法证实了头基的正确立体化学和优异的对映体纯度，并显著提高了产率、效率和合成经济性。
