Enantioselective Synthesis of a Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 5 (mGluR5) Receptor via Dynamic Kinetic Resolution of α‐Amino Ketones. Issue 13 (16th June 2016)

• Record Type: Journal Article
• Authors: González‐Bobes, Francisco; Hanson, Ronald; Strotman, Neil; Guo, Zhiwei; Goswami, Animesh
• Is Part Of: Advanced synthesis & catalysis. Volume 358:Issue 13(2016)
• Page Start: 2077
• Page End: 2082
• Publication Date: 2016-06-16
• Subjects: asymmetric synthesis -- biotransformations -- homogenous catalysis -- regioselectivity -- umpolung; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201600329
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: The concise synthesis of a pharmaceutical candidate is described. The chiral core of the molecule is assembled using an aza‐benzoin condensation and a dynamic kinetic resolution (DKR) as the key reactions. This enables superb control of the regio‐, diastereo‐ and enantioselectivity of the synthesis. Both biocatalysts and transition metal catalysts are remarkably effective in the key asymmetric reduction step. Similar approaches could be considered in the synthesis of other 1, 2‐amino alcohols where traditional approaches based on functionalization of alkenes, epoxides or aziridines may suffer from selectivity issues. Abstract :