Asymmetric Alkylation of Ketones Catalyzed by Engineered TrpB

Abstract

Supporting information for this article is given via a link at the end of the document.

Molecular and Structural Basis for Cγ−C Bond Formation by PLP‐Dependent Enzyme Fub7

“…β‐keto acids or aldehydes) have only one α‐site for deprotonation. In a similar vein, asymmetric alkylation of ketones was recently demonstrated with an engineered variant of TrpB, [15] but the ketone substrates used therein also possessed only a single deprotonation site. Consequently, regioselective α‐alkylation of ketones remains an unexplored area for PLP‐dependent enzymes.…”

Biocatalytic Construction of Chiral Pyrrolidines and Indolines via Intramolecular C(sp3)–H Amination

“…In a preparative-scale reaction, the enzyme afforded α-amino ester 5 as a white solid in 43% yield with identical selectivities. In another demonstration, Thermotoga maritima tryptophan synthase ( Tm TrpB) variant TmE3 from a ketone alkylation lineage coupled 4a and l -serine to provide the N -alkylated noncanonical amino acid 6 in 30% isolated yield with excellent diastereoselectivity (>94:6 dr). These biocatalytic derivatization reactions using engineered enzymes demonstrate how complexity can be built rapidly and under mild conditions for the asymmetric synthesis of N -heterocycle-containing molecules.…”

Engineered Biocatalytic Synthesis of β‐N‐Substituted‐α‐Amino Acids

“…[16,17] More recently, biocatalytic systems have been leveraged to synthesize ncAAs that avoid protecting group manipulations and a variety of CÀ C bond forming transformations have been developed (vida infra). [18][19][20][21][22][23][24][25][26][27] Despite these successes, methods that yield N-containing sidechains have been limited. The potential reversibility of CÀ N bond formation presents a distinct challenge and, if it were overcome, would enable access to new classes of densely functionalized ncAAs.…”

“…Traditional synthetic methods typically rely on protecting group manipulations to attenuate undesired reactions with the amine and carboxylic acid functionalities and must assiduously avoid epimerization of the chiral center [16,17] . More recently, biocatalytic systems have been leveraged to synthesize ncAAs that avoid protecting group manipulations and a variety of C−C bond forming transformations have been developed (vida infra) [18–27] . Despite these successes, methods that yield N ‐containing sidechains have been limited.…”