Synthetic studies utilizing podocarpic acid

Abstract

The ketoester, 3-ethoxycarbonyl-12-methoxy-5βH-18,19-bisnor-podocarpa-8,11,13-trien-4-one(80). The numbering used throughout this thesis is that proposed by J.W. Rowe (personal communication to Dr. R. C. Cambie) in 'The Common and Systematic Nomenclature of Cyclic Diterpenes', 3rd Revision, Oct. 1968, to be submitted to the IUPAC Commission on Organic Nomenclature has been prepared from 12-hydroxypodocarpa-8,11,13-trien-19-oic acid (1), via the C4 ketones (76) and (77). Both of these isomers were obtained from the methoxyalkene (11), which was isolated in a pure form during selective epoxidation of the methoxyalkene mixture (11 - 13) obtained from the decarboxylation of 12-methoxypodocarpa-8,11,13-trien-19-oic acid (2) with lead tetraacetate. This reaction has been investigated, and a mechanism accounting for the formation of nondecarboxylation products is proposed. The unsaturated ketoester (102) was prepared in low yield via the saturated C12 ketone (24), obtained from 12-hydroxypodocarpa-8,11,13-trien-19-oic acid (1) by Birch reduction of the aromatic ring. A number of ring A epoxide derivatives of the acid(1) were prepared and cleaved by a variety of reagents to give the 3-oxygenated derivatives (145), (146), and (152), together with compounds possessing a contracted ring A. Some ring B lactone derivatives of the acid (1) were prepared, and their stereochemistry and conformation were determined by n.m.r. spectroscopy. The conformation of some ring B-substituted derivatives was also determined by n.m.r. methods. The bromination of some 7-ketopodocarpa-8,11,13-triene derivatives was investigated, and reasons are advanced for the non-stereospecific reactions observed in some cases.