Synthesis of (aryl or arylalkyl)-3-hydroxy propionic acids and a

Details Synthesis of (aryl or arylalkyl)-3-hydroxy propionic acids and a Synthesis of (aryl or arylalkyl)-3-hydroxy propionic acids and a

1989-09-25

1990-05-01

Lilling, Herbert J.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Preparing oxygen-containing organic compound

435156, 435197, 435280, 435876, C12P 742, C12R 139, C07P 4100

Patent

active

049217984

ABSTRACT:
R- and S-1-Phenyl-1,3-propanediol, each of high optical purity, were prepared by a chemoenzymatic sequence starting with ethyl benzoylacetate. The first step was a catalytic hydrogenation of the .beta.-ketoester conducted at room temperature. The enzymatic hydrolysis of the resulting hydroxyester proceeded in a facile manner using a commercial preparation of the lipase from Pseudomonas fluorescens. The enzymatic hydrolysis proceeded at a moderate rate (350 mg lipase/0.10 mol of racemic ester required a 20-hour reaction time with an enantiomeric rate ratio (E value) of 36). The hydrolysis was run to 45-50% conversion to afford isolated S-3-phenyl-3-hydroxypropionic acid of 85-90% ee after separation from the residual ester (aqueous base extraction). The optical purity of the hydroxy acid was determined by conversion to the methyl ester (CH.sub.3 I, KHCO.sub.3, acetone), and derivatization with S-MTPA-Cl, and .sup.1 H NMR analysis. A single recrystallization of the isolated acid afforded optically pure (>98% ee) S-3-phenyl-3-hydroxypropionic acid in an overall 36% yield from the racemic ester. The acid was reduced with borane in THF to afford optically purs S-diol in 97% yield after crystallization. The overall sequence proceeded in 34% total yield from racemic ester with an additional 45-55% recovered as the antipodal ester. This antipodal ester is obtained in 85-95% ee, and the corresponding hydroxy-acid was readily obtained (NaOH), CH.sub.3 OH/H.sub.2 O) and recrystallized to optical purity. Reduction then afforded R-1-phenyl-1,3-propanediol in 30% to overall yield from racemic ester.

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