Diastereoselective Hydrolysis of Branched Malonate Diesters by Porcine Liver Esterase: Synthesis of 5‐Benzyl‐Substituted Cα‐Methyl‐β‐proline and Catalytic Evaluation. Issue 20 (31st May 2017)

• Record Type: Journal Article
• Authors: Kotapati, Hari Kiran; Robinson, Jamarii D.; Lawrence, Daniel R.; Fortner, Kimberly R.; Stanford, Caleb W.; Powell, Douglas R.; Wardenga, Rainer; Bornscheuer, Uwe T.; Masterson, Douglas S.
• Is Part Of: European journal of organic chemistry. Issue 20(2017)
• Page Start: 3009
• Page End: 3016
• Publication Date: 2017-05-31
• Subjects: Enzyme catalysis -- Diastereoselectivity -- Organocatalysis -- Porcine Liver Esterase -- Hydrolysis; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201700605
• Languages: English
• ISSNs: 1434-193X

Abstract

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 (3 R, 5 S )‐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, (3 S, 5 S )‐1c was prepared by enzymatic hydrolysis using PLE isoenzyme 3 and tested for its catalytic activity in the Mannich reaction. Amino acid, (3 S, 5 S )‐1c catalyzed the Mannich reaction between isovaleraldehyde and an α‐imino ester yielding the " anti " selective product with an optical purity of 99 % ee . Abstract : Recombinant Porcine Liver Esterase (PLE) hydrolyses optically pure chiral malonate diesters to provide diastereoenriched half‐esters (isoenzymes PLE1–6, 5:1 dr ; PLE isoenzyme 3, 4:1 dr ). Stereoselective cyclization then gives novel proline analogues, which are excellent catalysts in the Mannich reaction between aldehydes and α‐imino esters to provide anti ‐selective products in 23:1 dr and 99 % yield.