Chung Sung-Kee, Kwon Yong-Uk, Shin Jung-Han, Chang Young-Tae, Lee Changgook, Shin Boo-Gyo, Kim Kyung-Cheol, Kim Mahn-Joo
Department of Chemistry, Division of Molecular and Life Sciences, Pohang University of Science & Technology, Pohang 790-784, South Korea.
J Org Chem. 2002 Aug 9;67(16):5626-37. doi: 10.1021/jo0257694.
Since the discovery of D-myo-inositol 1,4,5-trisphosphate, which plays a pivotal role as a second messenger in transmembrane signaling, the scope of the phosphoinositide-based signaling processes has been continually expanding. However, the clear understanding of the molecular signal transduction mechanisms including the functions of newly found IP(n) is still lacking. As a continuing effort to our previously reported syntheses of all possible 39 optically inactive regioisomers of myo-inositol phosphates (IP(n); n = 1-6), we synthesized all possible optically active regioisomers of myo-IP(3) and myo-IP(4) using chiral IBz(3)s and IBz(2)s, respectively. A series of procedures involving CRL-catalyzed enzymatic resolution of racemic 1,2:5,6-di-O-isopropylidene-myo-inositol and base-catalyzed benzoyl migration in tri- and dibenzoyl-isopropylidene-myo-inositol afforded eight enantiomeric pairs of IBz(3) and six enantiomeric pairs of IBz(2), respectively. Phosphorylation of these intermediates by the phosphitylation and oxidation procedure gave the target products.
自从发现 D-肌醇 1,4,5-三磷酸酯（它作为跨膜信号传导中的第二信使发挥关键作用）以来，基于磷酸肌醇的信号传导过程的范围一直在不断扩大。然而，对于包括新发现的 IP(n) 功能在内的分子信号转导机制仍缺乏清晰的认识。作为我们之前报道的合成肌醇磷酸酯（IP(n)；n = 1 - 6）所有 39 种光学无活性区域异构体的持续努力，我们分别使用手性 IBz(3) 和 IBz(2) 合成了肌醇三磷酸酯（myo-IP(3)）和肌醇四磷酸酯（myo-IP(4)）的所有可能的光学活性区域异构体。一系列程序包括外消旋 1,2:5,6-二-O-异亚丙基-肌醇的 CRL 催化酶促拆分以及三苯甲酰基和二苯甲酰基异亚丙基-肌醇中的碱催化苯甲酰基迁移，分别得到了八对对映体的 IBz(3) 和六对对映体的 IBz(2)。通过亚磷酸酯化和氧化程序对这些中间体进行磷酸化得到目标产物。
