Department of Chemistry, School of Science, The University of Tokyo, Hongo, Tokyo 113-0033, Japan.
Org Lett. 2013 Jun 7;15(11):2869-71. doi: 10.1021/ol401101u. Epub 2013 May 23.
In response to Berkeš's report revising the stereochemistry of HPA-12, an important ceramide-trafficking inhibitor that was discovered and synthesized and its stereochemistry determined in 2001, the synthesis and the stereochemistry were reinvestigated. A large-scale synthetic method for HPA-12 based on a Zn-catalyzed asymmetric Mannich-type reaction in water was developed. Single crystals of HPA-12 for X-ray crystallographic analysis were obtained from ethyl propionate/n-hexane, and the stereochemistry was definitely determined to be 1R,3S, consistent with Berkeš's revised structure.
针对 Berkeš 对 HPA-12 立体化学的修正报告，HPA-12 是 2001 年发现并合成的一种重要的神经酰胺转运抑制剂，其立体化学结构也已确定。本研究对其进行了重新合成和立体化学研究。开发了一种基于水相 Zn 催化不对称 Mannich 型反应的 HPA-12 大规模合成方法。通过从丙酸乙酯/正己烷中获得的 HPA-12 单晶进行 X 射线晶体学分析，确定其立体化学结构为 1R,3S，与 Berkeš 修正后的结构一致。
