Study of the chemistry of 2,1-benzothiazines and toward the total synthesis of elisapterosin B

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Using enantiomerically pure benzothiazines as templates, enantiomerically pure cyclobutanes were prepared. Such compounds are potentially interesting synthetic intermediates. The sequence developed for the preparation of these compounds, as well as some of their chemistry, is described. Treatment of certain benzothiazines bearing allylic bromides side chains with indium tribromide resulted in the formation of eight-membered rings in addition to the expected six-membered rings. Several attempts have been tried to approach the total synthesis of elisapterosin B, an important antitubercular and antimalarial marine natural product. Several methods have been tested: a diastereoselective intramolecular Friedel-Crafts alkylation reaction, an E-selective olefin cross-metathesis, and an asymmetric intermolecular Michael addition. A high diastereoselective methanesulfonic acid-catalyzed IFCA reaction of benzothiazine diene has been successfully used in total synthesis of pseudoteroxazole in the Harmata group. Seventeen benzothiazine dienes have been synthesized to study the factors that inference diastereoselectivity. Transition states were proposed and discussed. Protonation of benzothiazine was also studied via ¹H and ¹³C NMR spectrum.