Studies of the chemistry of 2,1-benzothiazines and an approach to the synthesis of antitubercular natural products.

摘要

The intramolecular, stereoselective conjugate addition of sulfoximine carbanions to alpha,beta-unsaturated esters was developed. It was demonstrated that the reaction is general and stereospecific. This extraordinary methodology is very powerful in establishing a stereogenic center at a benzylic position. Expanding on this method led to efficient formal total syntheses of (+)-curcuphenol and (+)-curcumene.; We are interested in the synthesis of a variety of natural products, which have related structures and are known to have antituberculosis activity. (+)-Erogorgiaene, a highly potent antitubercular diterpene, can induce 96% growth inhibition for Mycobacterium tuberculosis H37 Rv at 12.5 mug/mL, which was formally synthesized by benzothiazine and triazene chemistry. Two diastereoisomers of erogorgiaene were also prepared by a stereoselective, intramolecular Michael addition of sulfoximine carbanions to alpha,beta-unsaturated esters, a diazo Heck coupling reaction, and a stereoselective radical cyclization.; Pseudopteroxazole, another potent antitubercular member of the amphilectane class of diterpenes, was synthesized through a highly convergent strategy. The synthesis relied heavily on our development of stereoselective, intramolecular additions of sulfoximine carbanions to alpha,beta-unsaturated esters, a completely stereoselective intramolecular Friedel-Crafts alkylation, and an iridium-catalyzed asymmetric hydrogenation.; A novel procedure to conduct N-arylation of aryl chlorides with a sulfoximine in a short time under the influence of microwave irradiation was studied. The reactions can be performed on the less reactive, lower cost and more widely available aryl chlorides.