Journal of Organic Chemistry 2012-11-02

Total synthesis of pactamycin and pactamycate: a detailed account.

Stephen Hanessian, Ramkrishna Reddy Vakiti, Stéphane Dorich, Shyamapada Banerjee, Benoît Deschênes-Simard

Index: J. Org. Chem. 77(21) , 9458-72, (2012)

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Abstract

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.