- Lipase-catalyzed practical synthesis of (R)-1-benzyl-3-hydroxy-2,5-pyrrolidinedione and its related compounds
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A practical method for preparing (R)-1-benzyl-3-hydroxy-2,5-pyrrolidinedione (1) was investigated by the use of the enzymatic hydrolysis of its acetate (2a). Among several hydrolases examined here, lipase PS from Pseudomonas cepacia gave the best result: In a mixed solvent (1:1 v/v) of dioxane and a phosphate buffer (pH 7), the hydrolysis took place smoothly with a high enantioselectivity (E > 3000). Several 3-alkanoyl derivatives of 1 were subjected to the lipase PS-catalyzed hydrolysis. The chain length of the alkanoyl does not noticeably influence the reaction rate or the enantioselectivity. In contrast, the hydrolysis of the 1-benzoyl derivative proceeded slowly with a low enantioselectivity (E = 19). The syntheses of optically active 3-hydroxypyrrolidines and 3-hydroxypiperidines were also achieved under the reaction conditions similar to the lipase PS-catalyzed hydrolysis of 2a.
- Tomori, Hiroshi,Shibutani, Kuniko,Ogura, Katsuyuki
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- Preparation of enantiomerically pure N-heterocyclic amino alcohols by enzymatic kinetic resolution
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Abstract The synthesis of both enantiomers of N-benzyl-3-hydroxypyrrolidine and N-benzyl-3-hydroxypiperidine via enzymatic kinetic resolution of the corresponding racemic esters is described. Various commercially available hydrolases were studied as biocatalysts in native and immobilized form. The best results were obtained with lipases PS, AK, CAL-B and with protease Alcalase, which were active and selective for the kinetic resolutions of racemic esters (E > 100). Under optimized reaction conditions, highly enantiomerically enriched (up to 99.5% ee) resolution products were obtained. Lipase and protease showed opposite enantiopreference on the esters, allowing the preparation of both enantiomers of the target compounds. Semi-continuous reactions in column reactors with immobilized biocatalysts were also performed with high enantioselectivities. Inversion of the configuration at C(3) of N-benzyl-3-hydroxypyrrolidine was quantitatively effected in a short number of steps.
- Tofani, Giorgio,Petri, Antonella,Piccolo, Oreste
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p. 638 - 643
(2015/08/03)
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