A Simple Enantioconvergent and Chemoenzymatic Synthesis of Optically Active α‐Substituted Amides

Haloalkane dehalogenases: Biotechnological applications

“… Biotechnological applications of HLDs. Summary of reported applications of DatA [35], DbeA (Prudnikova et al, in preparation), DbjA [45, 47, 57, 61, 63, 125], DhaA [14, 44, 45, 47, 57, 66, 78, 79, 83, 87, 89, 92, 94, 96, 105–115, 125], DhlA [75, 76, 93, 97], DmbA [44, 89], DmlA [47], DpcA [38] and LinB [28, 44, 45, 47, 57, 61, 89, 95]. Abbreviations: BSA, bovine serum albumin; CB, 1‐chlorobutane, DCA; 1,2‐dichloroethane; DKR, dynamic kinetic resolution; KR, kinetic resolution; POI, protein of interest; TCP, 1,2,3‐trichloropropane; TEV, cleavage site for TEV protease.…”

“…The discovery of high enantioselectivity of HLDs (Supporting information, Table S3) has opened up the possibility to utilize HLDs to prepare optically pure ( S )‐β‐bromoalkanes, ( S )‐β‐alcohols, ( S )‐α‐brominated esters, ( S )‐α‐hydroxyesters [45, 57], ( S )‐α‐bromoamides and ( S )‐α‐hydroxyamides [47], useful building blocks in the production of pharmaceuticals. For instance, ( S )‐2‐pentanol is an intermediate in the synthesis of potential anti‐Alzheimer's disease drugs [59], ethyl ( S )‐2‐hydroxypropionate is used for preparation of lofexidine [60], and optically pure amides are precursors of non‐natural peptides, vitamins and antibiotics [61] (Fig. 5).…”

“…> 99%, E > 100), further requirements for the application of enzyme to a biocatalytic process have been proposed: (i) conversion of more than 98%; (ii) substrate loading higher than 100 g L –1 ; (iii) substrate/biocatalyst ratio higher than 50 with maximal biocatalyst loading 5 g L –1 ; and (iv) reaction time less than 24 h [62]. Due to the character of kinetic resolution of racemic substrates, the theoretical yield is limited to 50%, unless an additional chemical or enzymatic process [61] or racemization of the substrate [63] is used. Activation of the hydroxyl group of three different ( S )‐α‐hydroxyamides by methanesulfonyl chloride has enabled the enantioconvergent chemoenzymatic synthesis of optically active N ‐alkyl ( R )‐α‐azidoamides, N ‐alkyl ( R )‐α‐benzylaminoamides, N ‐alkyl ( R )‐α‐phenoxyamides and N ‐alkyl ( R )‐α‐ethylthioamides [61] (Fig.…”

DOTMA-based amides (DOTMAMs) as a platform for the development of PARACEST MRI contrast agents

“…24 With electrophiles 15a-18a in hand we investigated the alkylation of cyclen. Mixtures of di-, tri-and tetrasubstituted cyclens have been obtained, when electrophiles 15a-17a were used.…”

Why Leave a Job Half Done? Recent Progress in Enzymatic Deracemizations

“…[123] In this study, α-bromoamides reacted with high enantioselectivity in the presence of haloalkane dehalogenase from Bradyrhizobium japonicum USDA110 (DbjA), affording a homochiral mixture consisting of the remaining (S)-brominated substrate enantiomer and the (S)-alcohol product coming from the inverting reaction over the (R)-enantiomer (Scheme 21). Then, after mesylation, the α-bromide and the α-mesyloxy amides were finally treated with several nucleophiles in a S N 2 process to achieve the substituted (R)-amides.…”