The chemistry of pseudomonic acid. Part 8. Electrophilic substitutions at C-2 and C-15 of the pseudomonic acid nucleus by means of lithium dienolates

Abstract

The regiochemistry of substitution at C-2 (α) and C-15 (γ) of lithium dienolates (2) derived from esters of manic acid (1d) depends on the nature of the electrophile. Substitution at C-2 affords diastereoisomeric mixtures of the deconjugated esters (3). The stereochemistry of reconjugation can be controlled. The ester (3d) when heated with hindered bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) favours formation of methyl 2-methylisomonate (4f) whilst, in contrast, use of potassium t-butoxide favours the biologically active methyl 2-methylmonate (1 m).