Sustainable Biocatalytic Synthesis of (S)-β-Nitro Alcohols using a Promiscuous (R)-Selective Hydroxynitrile Lyase

Abstract

A chiral β-nitroalcohol possesses two versatile, functional groups, a nitro and a hydroxyl, attached to vicinal carbon centers of which either one or both are asymmetric. They are essential precursors to many synthetically useful structural motifs and pharmaceuticals. The potential to transform both the nitro and hydroxyl group in a β-nitroalcohol structure could produce a diverse range of synthetic molecules with one or more different functional groups. The nitro group can be altered to amine, carbonyl, nitrile, nitrile oxide, oxime, hydroxylamine, etc.1 Chiral vicinal amino alcohols that are key building blocks of a number of β-blockers used to cure cardiovascular diseases are synthesized by a simple reduction of the nitro group of corresponding chiral β-nitroalcohols.2 The nitro group of a β-nitroalcohol is converted to a carbonyl using Nef reaction to produce α-hydroxy carbonyl.3 It undergoes denitration where the nitro group is replaced by a hydrogen.4 Similarly, the hydroxyl group can be subjected to elimination, Ritter reaction, oxidation, acetylation, etc. Simple elimination in case of a β- nitroalcohol produces nitro alkene.5 In Ritter reaction, the hydroxyl group reacts with a nitrile under acidic conditions and converts it into corresponding N-(β-nitro)amide.6 The hydroxyl group of a β-nitroalcohol can be derivatized, i.e., acetylated to produce acetylated nitroalcohol. A few examples of different drug molecules and natural products for whom (S)-β-nitroalcohols happened to be structural components are, chelonin A7 (antimicrobial), and (S)-tembamide8 (anti-HIV), (S)-toliprolol, (S)-moprolol9, and (S)-propranolol10, (S)-norphenylephrine11 (β- adrenergic receptor blocking agents), (S)-sotalol12 (antiarrhythmic agents), and (S)- miconazole13 (antifungal) (Figure 1.1, upper).