Diastereoselective Hydrolysis of Branched Malonate Diesters by Porcine Liver Esterase: Synthesis of 5-Benzyl-Substituted C^α-Methyl-β-proline and Catalytic Evaluation

Authors

Hari Kiran Kotapati, University of Southern MississippiFollow
Jamarii D. Robinson, University of Southern Mississippi
Daniel R. Lawrence, University of Southern Mississippi
Kimberly R. Fortner, University of Southern Mississippi
Caleb W. Stanford, University of Southern Mississippi
Douglas R. Powell, University of OklahomaFollow
Rainer Wardenga, Enzymicals AG
Uwe T. Bornscheur, University of GreifswaldFollow
Douglas S. Masterson, University of Southern MississippiFollow

Document Type

Article

Publication Date

5-26-2017

Department

Chemistry and Biochemistry

School

Mathematics and Natural Sciences

Abstract

Malonate diesters with highly branched side chains containing a preexisting chiral center were prepared from optically pure amino alcohols and subjected to asymmetric enzymatic hydrolysis by Porcine Liver Esterase (PLE). Recombinant PLE isoenzymes have been utilized in this work to synthesize diastereomerically enriched malonate half‐esters from enantiopure malonate diesters. The diastereomeric excess of the product half‐esters was further improved in the later steps of synthesis either by simple recrystallization or flash column chromatography. The diastereomerically enriched half‐ester was transformed into a novel 5‐substituted C^α‐methyl‐β‐proline analogue (3R,5S)‐1c, in high optical purity employing a stereoselective cyclization methodology. This β‐proline analogue was tested for activity as a catalyst of the Mannich reaction. The β‐proline analogue derived from the hydrolysis reaction by the crude PLE appeared to catalyze the Mannich reaction between an α‐imino ester and an aldehyde providing decent to good diastereoselectivities. However, the enantioselectivities in the reaction was low. The second diastereomer of the 5‐benzyl‐substituted C^α‐methyl‐β‐proline, (3S,5S)‐1c was prepared by enzymatic hydrolysis using PLE isoenzyme 3 and tested for its catalytic activity in the Mannich reaction. Amino acid, (3S,5S)‐1c catalyzed the Mannich reaction between isovaleraldehyde and an α‐imino ester yielding the “anti” selective product with an optical purity of 99 %ee.

Publication Title

European Journal of Organic Chemistry

Volume

2017

Issue

20

First Page

3009

Last Page

3016

Recommended Citation

Kotapati, H. K., Robinson, J. D., Lawrence, D. R., Fortner, K. R., Stanford, C. W., Powell, D. R., Wardenga, R., Bornscheur, U. T., Masterson, D. S. (2017). Diastereoselective Hydrolysis of Branched Malonate Diesters by Porcine Liver Esterase: Synthesis of 5-Benzyl-Substituted C^α-Methyl-β-proline and Catalytic Evaluation. European Journal of Organic Chemistry, 2017(20), 3009-3016.
Available at: https://aquila.usm.edu/fac_pubs/14957