Part I. Studies of Stereoselective C-H Amination, Part II. Synthetic Studies of Edaxadiene, Part III. Studies towards the Synthesis of Alchivemycin A, Part IV. The Formal Synthesis of (-)-Englerin A by RRCM and Etherification

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Lee, Jungyong
The Graduate School, Stony Brook University: Stony Brook, NY.
Part I. Various polysaccharides and glycosidic antibiotics including anthracycline and vancomycin have been widely used to treat cancer or infection. Amino sugars are often found in their structures and play an important role in biological activities. C-H amination is one of valuable methods to streamline the synthesis of C-N bond. Regio-, stereoselective C-H amination has been studied to produce useful amino sugars from glycals and alkynol carbamates. Part II. Edaxadiene was considered as a new diterpene that had biological activities to inhibit the infection process of Mycobacterium tuberculosis. We describe a design to access a bicyclic backbone, which is the core structure of this compound by an intramolecular Diels-Alder (IMDA) reaction. Part III. Progress toward the synthesis of a key moiety of alchivemycin A, which was isolated from a plant-derived actinomycete Streptomyces sp and displayed selective and potent antibiotic activity against Micrococcus luteus, has been focused on the construction of a bicyclic structure by the IMDA reaction. Part IV. (-)-Englerin A is a natural product from phyllathus engleri, a plant common in east Africa. It showed an interesting biological activity in its ability to inhibit the growth of kidney cancer cell lines in the NCI-60 screen. The useful bioactivity and unique structure of (-)-englerin A have inspired many scientists to develop synthetic approaches to understand the structure-activity relationship (SAR). We reported the formal synthesis of (-)-englerin A and established an efficient synthetic route by a relay ring closing metathesis (RRCM) reaction and etherification. This study includes the efficient opening of the epoxide ring of a Β-substituted Α-epoxy alcohol under the lithium acetylide reagent, the relay ene-yne-ene metathesis method for the preparation of a diene that is disubstituted on both ends, and the transannular stereo- and regio-specific oxymercuration of the C-6, C-7 olefin in the guaiane ring system.
370 pg.