Optimizing the Synthesis Strategy of the Chlorinated Chain Characteristic to the Enacyloxin Series Using Models.

Abstract

In this paper are presented the results of the preliminary studies conducted on two model substrates that allowed the testing of various strategies and set the proper conditions that thereafter culminated in the synthesis of the C1-C23 chain of enacyloxin-IIa and its congeners. Innovative strategic options were explored on each model allowing the stereochemical control of the following two elements: (a) the 2E, 4E, 6E, 8E, and 10Z chlorinated undecapentaenoic chain, thanks to Z-selective Kaneda's alkyne allylchlorination and an E-selective Pd/Cu allene-alkyne coupling and (b) the unusual syn-anti -OH/-Cl/-OCONH2 C17-C19 triad, thanks to a highly diastereoselective Mukaiyama aldol reaction.