625471-18-3Relevant articles and documents
A Rapid Selection Procedure for Simple Commercial Implementation of ω-Transaminase Reactions
Gundersen, Maria T.,Tufvesson, P?r,Rackham, Emma J.,Lloyd, Richard C.,Woodley, John M.
, p. 602 - 608 (2016)
A stepwise selection procedure is presented to quickly evaluate whether a given ω-transaminase reaction is suitable for a so-called "simple" scale-up for fast industrial implementation. Here "simple" is defined as a system without the need for extensive process development or specialized equipment. The procedure may be used when investment in intensive process development cannot be justified or when rapid execution is paramount, for applications such as small singular batches. The three-step evaluation procedure consists of: (1) thermodynamic assessment, (2) biocatalyst activity screening, and (3) determination of product inhibition. The method is exemplified with experimental work focused on two products: 1-(4-bromophenyl)ethylamine and (S)-(+)-3-amino-1-Boc-piperidine, synthesized from their corresponding pro-chiral ketones each with two alternative amine donors, propan-2-amine, and 1-phenylethylamine. Each step of the method has a threshold value, which must be surpassed to allow "simple" implementation, helping select suitable combinations of substrates, enzymes, and donors. One reaction pair, 1-Boc-3-piperidone with propan-2-amine, met the criteria of the three-step selection procedure and was subsequently run at 25 mL scale synthesizing (S)-(+)-3-amino-1-Boc-piperidine at concentrations up to 75 g/L. However, the highest product yield (70%) was obtained at a lower substrate concentration of 50 g/L.
The identification and use of robust transaminases from a domestic drain metagenome
Leipold, Leona,Dobrijevic, Dragana,Jeffries, Jack W.E.,Bawn, Maria,Moody, Thomas S.,Ward, John M.,Hailes, Helen C.
, p. 75 - 86 (2019/01/11)
Transaminases remain one of the most promising biocatalysts for use in chiral amine synthesis, however their industrial implementation has been hampered by their general instability towards, for example, high amine donor concentrations and organic solvent content. Herein we describe the identification, cloning and screening of 29 novel transaminases from a household drain metagenome. The most promising enzymes were fully characterised and the effects of pH, temperature, amine donor concentration and co-solvent determined. Several enzymes demonstrated good substrate tolerance as well as an unprecedented robustness for a wild-type transaminase. One enzyme in particular readily accepted IPA as an amine donor giving the same conversion with 2-50 equivalents, as well as being tolerant to a number of co-solvents, and operational in up to 50% DMSO-a characteristic as yet unobserved in a wild-type transaminase. This work highlights the value of using metagenomics for biocatalyst discovery from niche environments, and here has led to the identification of one of the most robust native transaminases described to date, with respect to IPA and DMSO tolerance.
3-AMINOPIPERIDINES AND 3-AMINOQUINUCLIDINES AS INHIBITORS OF MONOAMINE UPTAKE
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Page 60, (2010/02/10)
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, which are useful for the inhibition of the uptake of one or more physiologically active monoamines (serotonin, norepinephrine, and dopamine).