Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio- and Stereoselective Acylation of Alcohols

Abstract

Geminal diacetates have been used as sustainable acyl donors for enzymatic acylation of chiral and nonchiral alcohols. Especially, it was revealed that geminal diacetates showed higher reactivity than vinyl acetate for hydrolases that are sensitive to acetaldehyde. Under optimized conditions for enzymatic acylation, several synthetically relevant saturated and unsaturated acetates of various primary alcohols were obtained in very high yields up to 98% without E/Z isomerization of the double bond. Subsequently, the acyl donor was recreated from the resulting aldehyde and reused constantly in acylation. Therefore, the developed process is characterized by high atomic efficiency. Moreover, it was shown that acylation using geminal diacetates resulted in remarkable regioselectivity by discriminating among the primary and secondary hydroxyl groups in 1-phenyl-1,3-propanediol providing exclusively 3-acetoxy-1-phenyl-propan-1-ol in good yield. Further, enzymatic kinetic resolution (EKR) and chemoenzymatic dynamic kinetic resolution (DKR) protocols were developed using geminal diacetate as an acylating agent, resulting in chiral acetates in high yields up to 94% with enantiomeric excesses exceeding 99%.

Relationship between Structure and Antibacterial Activity of α-Aminophosphonate Derivatives Obtained via Lipase-Catalyzed Kabachnik−Fields Reaction

“…The Kabachnik–Fields reaction is the most efficient method for the formation of carbon−phosphorus bonds using an aldehyde, amine, and H -phosphite. A number of other synthetic approaches have also been reported for the preparation of α-aminophosphonates [ 7 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. These methods are generally conducted in the presence of various organic and inorganic bases [ 56 , 57 , ...…”

“…As a continuation of our research on seeking new catalytic activities of hydrolases [ 74 , 75 , 76 , 77 , 78 , 79 , 80 , 94 , 95 ], we focused our efforts on elaborating a sustainable metal-free method towards desired α-aminophosphonates 1 – 16 ( Figure 2 ).…”

Chirality: An inescapable concept for the pharmaceutical, bio‐pharmaceutical, food, and cosmetic industries

“…The worldwide flavor and fragrance ingredients and finished products market is expected to increase at a compound annual growth rate of 4.0% from $1.4 trillion in 2019 to $1.8 trillion in 2024 [159]. Aroma (plant origin) and musk (animal origin) compounds are the two main types of natural fragrances.…”

Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate–Enzyme Intermediate

“…Nowadays, emphasis is put on the development of protocols giving access to a set of synthetically-relevant products in one-pot processes with great atom efficiency. Therefore, in the course of our studies on the intensification of enantioselective reactions [ 10 , 11 ], we decided to study if it was possible to combine two enantiodivergent steps in one process and to optimize it for preparative purposes.…”