The overall objectives of this proposal are to advance the art and science of organic synthesis in the context of the synthesis of biologically active natural products. The chemical targets outlined in this proposal possess anticancer, antibiotic, antioxidative, antiviral, and antifungal activity, and they include carbazomycin A and B, carazostatin, hyellazole, trp-P-1 and P-2, tabernaemontanine, dregamine, cis- and trans-trikentrin A, 5,6-dibromotryptamine, 2,3,5,6- tetrabromoindole, antiostatin A1, minovincine, and morphine pyrolysate compounds. The syntheses of these natural products involves the construction and novel cycloaddition chemistry of these fused heterocyclic ring systems: furo[3,4-b]indoles, furo[3,4-b]pyrroles, and pyrrolo[3,4b]indoles, the second of which is an unknown ring system. Two new one-step syntheses of pyrrolo[3,4b]indoles are described. New chemistry is proposed for the synthesis of indoles, carbazoles, and carbolines, and new applications of the use of the mesoionic """"""""munchnones"""""""" (1,3-oxazolium-5-olates) in synthesis are described. The important carbazole antioxidant antiostatins are 100 times more potent than Vitamin E, and such free radical inhibitors are important in the prevention of cancer, stroke, cataracts, brain dysfunction, immune system decline, and aging. Several natural products are synthesized for the first time, including tabernaemontanine, 5,6-dibromotryptamine, 2,3,5,6-tetrabromoindole, and two morphine pyrolysate indoles. A simple route to the as yet unisolable indole-2,3-quinodimethane is proposed that will lead to the isolation of this diene for the first time.
| Liu, Yanbing; Gribble, Gordon W (2002) Syntheses of polybrominated indoles from the red alga Laurencia brongniartii and the brittle star Ophiocoma erinaceus. J Nat Prod 65:748-9 |
| Gribble, Gordon W; Jiang, Jun; Liu, Yanbing (2002) An efficient synthesis of 4-(phenylsulfonyl)-4H-furo[3,4-b]indoles. J Org Chem 67:1001-3 |
