Total Synthesis of Pactamycin and Pactamycate: A Detailed Account

This article describes synthetic studies that culminated
in the
first total synthesis of pactamycin and pactamycate and, in parallel,
the two known congeners, de-6-MSA-pactamycin and de-6-MSA-pactamycate,
lacking the 6-methylsalicylyl moiety. Starting with l-threonine
as a chiron, a series of stereocontrolled condensations
led to a key cyclopentenone harboring a spirocyclic oxazoline. A series
of systematic functionalizations led initially to the incorrect cyclopentanone
epoxide, which was “inverted” under solvolytic conditions.
Installation of the remaining groups and manipulation of the oxazoline
eventually led to pactamycin, pactamycate, and their desalicylyl analogues.

本文报道了一系列合成研究工作，最终首次实现了帕他霉素（pactamycin）与帕他霉烷（pactamycate）的全合成；与此同时，还同步完成了两种已知同系物——脱6-甲基水杨酰基帕他霉素（de-6-MSA-pactamycin）与脱6-甲基水杨酰基帕他霉烷（de-6-MSA-pactamycate）——的全合成，这两种同系物均缺失6-甲基水杨酰基（6-methylsalicylyl）结构片段。本研究以L-苏氨酸（L-threonine）作为手性合成子（chiron），通过一系列立体可控缩合反应得到了关键中间体——带有螺环恶唑啉（spirocyclic oxazoline）结构的环戊烯酮（cyclopentenone）。经一系列系统性官能团化反应后，最初得到了错误的环戊酮环氧化物（cyclopentanone epoxide），该中间体可在溶剂解条件（solvolytic conditions）下发生构型翻转。通过引入剩余官能团并对恶唑啉结构进行修饰改造，最终成功得到帕他霉素、帕他霉烷及其脱水杨酰基类似物（desalicylyl analogues）。