Synthesis and characterization of an oxazine and a library of amide derivatives of podocarpic acid

ORGN 422

Nicole John, njjohn24@yahoo.com1, Oladapo Bakare, obakare@howard.edu1, and Raymond J. Butcher, rbutcher@howard.edu2. (1) Department of Chemistry, Howard University, 525 Collge Street, Washington DC, DC 20059, (2) Chemistry Department, Howard University, 525 College St. NW, Washington, DC 20059
Podocarpic acid possesses the ring system common to most tricyclic diterpenoids and it is an attractive scaffold for chemical transformation into compounds with interesting biological activities. Some podocarpic acid analogs have been reported as cytokine release inhibitors and consequently as leads to the discovery of novel anti-inflammatory drugs. Structurally related abietane diterpenes have recently been reported to possess strong inhibitory activities against certain human tumors. We have designed the synthesis of several podocarpic acid derivatives for bioactivity studies. The reaction of podocarpic acid with dimethyl sulfate furnished 12-methoxy derivative which was subsequently converted to the acid chloride. Reaction of the acid chloride with several structurally diverse amines furnished the amide derivatives. Formation of the (3-bromopropyl) amide derivative was followed by an intramolecular cyclization leading to a novel oxazine derivative of podocarpic acid. The synthesis, infrared (IR), 1H-NMR and 13C-NMR spectroscopy, GC/MS and X-ray diffraction studies of these compounds are reported.
 

Bioorganic, Metal-Mediated Reactions, and Molecular Recognition
8:00 PM-10:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005