The transformation of levopimaric acid into warburganal

Abstract

The chiral resin acid levopimaric acid (1), isolated from pine oleoresin, is used as a starting material for the synthesis of (−)-warburganal (2). The synthesis proceeds via the endoperoxide of methyl levopimarate, which after ozonolysis, protection of the resulting aldehyde function, reduction, and treatment with sodium methoxide provides the tetranorditerpenoid 12a. The hemiacetal 12a is then transformed to a mixture of hemithioacetals. At this point the carbomethoxyl group at C-4 is reduced to a methyl group, and then a C-11, C-12 double bond is introduced. Ozonolysis followed by elimination of formic acid provides a mixture of olefins (27) that is hydroxylated at C-9. Removal of the protecting group then gives (−)-warburganal (2). The sequence requires 15 steps and the overall yield from levopimaric acid to warburganal is 2.7%.