Synthesis of Natural Products and Synthetic Methodologies
Research in the Magnus Lab is focused on the total synthesis of natural products. Alkaloids, terepenoids, ketolides, and other classes of natural products have all been completed in our labs. All of the current projects involve the development of new concise strategies and this, in course, frequently leads to the discovery of new reactions. These projects are summarized below.
Total Synthesis of Platensimycin: Discovered in 2006 by scientists in the Merck Research Laboratories, platensimycin is the first member of a new class of antibiotics. Platensimycin exhibits potent antibiotic properties toward gram-positive pathogens, working by inhibition of bacterial fatty acid biosynthesis.
Total Synthesis of Morphine: Morphine is an opiate alkaloid extracted from the unripe poppy seed capsule, and one of the most widely used drugs to alleviate severe post-operative and chronic pain. The presence of 5 rings, 5 contiguous stereocenters and a compact array of functionality makes the synthesis challenging. The first landmark synthesis was by Gates in 1953. Since then, at least 20 formal and total syntheses have been published; yet, no route seems promising for the industrial production of the opiate alkaloids.
Total Synthesis of Silvestrol: Isolated in 2004 from the twigs and fruits of Aglaia foveolata (Pannell), Silvestrol shows cytotoxic activity comparable to Taxol. No total synthesis of silvestrol has been published to date, but there have been numerous syntheses of the parent rocaglamide and the 1,4-dioxanyloxy fragment. Our strategy uses a Nazarov cyclization to form the cyclopenta[b]benzofuran skeleton.
Total Synthesis of Secu’amamine A: Secu’amamine A is a novel indolizidine alkaloid that belongs to the Securinega alkaloids. In 2003 Ohsaki and Kobayashi reported the structure of Secu’amamine isolated from Securinega suffruticosa var. amamiensis. Efforts towards the synthesis of Secu’amamine A are currently under way.
Total Synthesis of Cortistatin A: Cortistatin A is one of eleven anti-angiogenic steroidal alkaloids which were recently isolated from the marine sponge Corticium simplex. In preliminary screenings, cortistatin A exhibited highly selective anti-proliferative activity against human umbilical vein endothelial cells (HUVECs), and is thus a promising anti-tumor drug candidate.
Daphnicyclidin A: Isolated from extracts of Daphniphylum Humile, Daphnicyclidin shows cytotoxic activity against murine lymphoma L1210 (IC50, 0.8 μg/mL) and human epidermoid carcinoma KB (IC50, 6.0 μg/mL) cell lines in vitro. No syntheses have been published, to date.
