1. Synthesis of 1-Boc-3-fluoroazetidine-3-carboxylic acid
Eva Van Hende, Guido Verniest, Frederik Deroose, Jan-Willem Thuring, Gregor Macdonald, Norbert De Kimpe J Org Chem. 2009 Mar 6;74(5):2250-3. doi: 10.1021/jo802791r.
Synthetic strategies toward 3-fluoroazetidine-3-carboxylic acid, a new cyclic fluorinated beta-amino acid with high potential as building block in medicinal chemistry, were evaluated. The successful pathway includes the bromofluorination of N-(diphenylmethylidene)-2-(4-methoxyphenoxymethyl)-2-propenylamine, yielding 1-diphenylmethyl-3-hydroxymethyl-3-fluoroazetidine after reduction of the imino bond, ring closure, and removal of the 4-methoxybenzyl group. Changing the N-protecting group to a Boc-group allows further oxidation to 1-Boc-3-fluoroazetidine-3-carboxylic acid, a new fluorinated heterocyclic amino acid.
2. Carboxylic acid reductases in metabolic engineering
Neil Butler, Aditya M Kunjapur J Biotechnol. 2020 Jan 10;307:1-14. doi: 10.1016/j.jbiotec.2019.10.002. Epub 2019 Oct 16.
Carboxylic acid reductases (CARs) catalyze the conversion of carboxylic acids to aldehydes, which are a valuable class of chemicals for many consumer and industrial applications. CARs generally exhibit broad substrate specificity that encompasses aromatic, aliphatic, and di/tri-carboxylic acids, enabling the development of biosynthetic pathways to a wide array of potential aldehyde products. De novo synthetic pathways implementing CARs have enabled the production of sustainable aldehyde products or utilized highly reactive aldehydes as intermediates in the production of chemicals including amines, alcohols, and alkanes. Recent determination of crystal structures of the domains of three CARs has provided insight into the substrate binding and domain dynamics of CARs, which could enable future engineering efforts to both alter the specificity of CAR and expand its potential in future synthetic pathways. In this review, we summarize the current structural and mechanistic understanding of CARs including substrate and catalytic scope, their potential for future engineering, and the advantages and challenges of their application in de novo synthesis.
3. Directing carboxylic acid dehydrogenation
Yoshiharu Iwabuchi Science. 2021 Dec 3;374(6572):1199. doi: 10.1126/science.abm4457. Epub 2021 Dec 2.
A palladium ligand can activate carbon-hydrogen bonds yet avoid product olefin reactions.