Natural product synthesis and development of synthetic methodology

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The research proposal deals with (1) plans for the total synthesis of several biologically important and complex natural products and with the development of new synthetic methodology to deal with the constructional problems posed by these compounds, and (2) the development of general synthetic methods that should have wide applicability to a range of target substances. The main natural products are (1) CP-225,917, an anticancer and cholesterol-lowering substance; (2) marinopyrrole B, an unprecedented class of antibiotic; (3) coleophomone B, an inhibitor of an enzyme involved in bacterial cell wall synthesis; (4) sorbicillactone A, which shows selective anti-leukemic activity, and also has antiviral (HIV) and neuroprotective properties; and (5) MPC1001, which exhibits very powerful activity against a prostate cancer cell line. These natural products, besides having biological properties that identify them as important synthetic targets, also pose constructional problems that are of general occurrence and the solution to these problems will fill gaps in current technology. In relation to these target molecules, new routes to pyrroles, macrolactams and tricarbonyl compounds will be studied.