Fritz Theil

Enzymes in organic synthesis. Part 3. Synthesis of enantiomerically pure prostaglandin intermediates by enzyme-catalyzed transesterification of (1SR,2RS,5SR,6RS)-bicyclo[3.3.0]octane-2,6-diol with trichloroethyl acetate in an organic solvent

Since the pancreatin-catalyzed esterification of the diol (1) with 2,2,2-trichloroethyl acetate in tetrahydrofuran is significantly slower than the esterification of the enantiomer ent-(1), the diacetate ent-(3) can be obtained from the racemic diol rac-(1) in a chemical yield of 30–35% and an enantiomeric excess (e.e.) of 97– > 99%. When the remaining enantiomerically enriched diol (1) with an e.e. in the order of 55–68% was subjected once more to the pancreatin-catalyzed esterification its e.e. could be enhanced to 90%. Then acetylation and recrystallization afforded the diacetate (3) in a chemical overall yield of 37% and an e.e. of > 99%.

A three-step procedure for the conversion of γ-lactones into δ-lactones

γ-Lactones with a wide range of functional groups are transformed by a three-step procedure into the corresponding δ-lactones in an overall yield of up to 55%. The novel methodology involves the reduction of a γ-lactone to a γ-lactol followed by a Horner olefination with an excess of lithiated diethyl α-cyano-α-xdimethylaminomethylphosphonate to yield a mixture of E/Z-isomeric α-cyano enamines. Acidic hydrolysis of these intermediates affords the desired δ-lactones. By the same reaction sequence δ-lactones can be transformed into the corresponding Iµ-hydroxy carboxylic acids.