Part I: Design, synthesis, and reactivity of 1-hydrazinodienes for use in organic synthesis Part II: Studies toward a synthesis of the antibiotic platensimycin

The Diels-Alder reaction has provided the foundation for some of the most impressive achievements in natural product synthesis. It provides access to six-membered rings bearing up to four stereocenters in a single step. In addition, many functionalized dienes have been developed to further diversify the synthesized six-membered rings constitutionally. Our laboratory was inspired to design and synthesize a novel 1-hydrazinodiene, in the course of a natural product synthesis. Several 1-hydrazinodienes have been synthesized and demonstrated to successfully undergo asymmetric Diels-Alder reactions with excellent yields and stereoselectivity. The Diels-Alder adducts can be easily converted to diazenes that undergo 1,5-sigmatropic rearrangement to yield cyclohexene structures with a remote 1,4-stereochemical relationship, which may not be easily accessed through traditional Diels-Alder reactions. These dienes were applied in an efficient intermolecular Diels-Alder strategy toward trans-fused decalins, basic building blocks of more complex natural products.;Following the diene project, we studied a synthetic pathway toward a natural product platensimycin. Platensimycin is the most potent antibiotic that acts by inhibiting beta-ketoacyl-(acyl-carrier-protein) synthase II in bacterial type II fatty acid synthesis. It consists an unusual 3-amino-2,4-dihydroxybenzoic acid polar domain and a lipophilic tetracyclic ketolide domain. Our synthetic strategy features a Rh(II) catalyzed C--H bond insertion to generate a key five-membered ring, after which an intramolecular Diels-Alder reaction and a subsequent oxidative ring opening establishes the main skeleton of the natural product.