219 catalyzed by Pseudomonas fluorescence lipase was followed by protection of
the free alcohol to provide intermediate 220. After a series of protective group
transformations, alkene 221 was subjected to ozonolysis, and subsequent treatment
with Zn/AcOH gave hemiacetal 222 as a 1:1 diastereomeric mixture at the C2
position. Protection of hemiacetal 222 gave the protected hemiacetal as the sole
diastereomer with the defined stereochemistry. Reduction of the aldehyde and
subsequent iodination of the resulting alcohol gave iodide 223 as a synthetic
equivalent for the δ-lactone in mevinic acid analogues, 224.
A couple of template-directed approaches have been developed for the synthesis
of mevalonolactone [90]. In the first approach, the spiro-fused lactone 225
constructed from diacetone-D-glucose was subjected to a stereoselective epoxidation and then reduction to provide diol 226 (Scheme 46). Cleavage of the acetals
followed by exhaustive oxidation allowed the cleavage of the carbon skeleton from
the template, providing (R)-mevalonolactone 10 in moderate yield.
In another approach, ketone 228 was obtained in optically pure form by an
enzymatic desymmetrization and a stereoselective epoxidation [91] (Scheme 47). A
sequential reduction of epoxide and the carbonyl group gave diol 229, which was
Scheme 44 Synthesis of Prelog–Djerassi lactonic acid
Scheme 45 Preparation of a synthetic equivalent for the δ-lactone in mevinic acids
Synthesis of Saturated Six-Membered Ring Lactones
121
the free alcohol to provide intermediate 220. After a series of protective group
transformations, alkene 221 was subjected to ozonolysis, and subsequent treatment
with Zn/AcOH gave hemiacetal 222 as a 1:1 diastereomeric mixture at the C2
position. Protection of hemiacetal 222 gave the protected hemiacetal as the sole
diastereomer with the defined stereochemistry. Reduction of the aldehyde and
subsequent iodination of the resulting alcohol gave iodide 223 as a synthetic
equivalent for the δ-lactone in mevinic acid analogues, 224.
A couple of template-directed approaches have been developed for the synthesis
of mevalonolactone [90]. In the first approach, the spiro-fused lactone 225
constructed from diacetone-D-glucose was subjected to a stereoselective epoxidation and then reduction to provide diol 226 (Scheme 46). Cleavage of the acetals
followed by exhaustive oxidation allowed the cleavage of the carbon skeleton from
the template, providing (R)-mevalonolactone 10 in moderate yield.
In another approach, ketone 228 was obtained in optically pure form by an
enzymatic desymmetrization and a stereoselective epoxidation [91] (Scheme 47). A
sequential reduction of epoxide and the carbonyl group gave diol 229, which was
Scheme 44 Synthesis of Prelog–Djerassi lactonic acid
Scheme 45 Preparation of a synthetic equivalent for the δ-lactone in mevinic acids
Synthesis of Saturated Six-Membered Ring Lactones
121