Enantio-Complementary Continuous-Flow Synthesis of 2-Aminobutane Using Covalently Immobilized Transaminases

Heckmann, Christian M.; Dominguez, Beatriz; Paradisi, Francesca (2021). Enantio-Complementary Continuous-Flow Synthesis of 2-Aminobutane Using Covalently Immobilized Transaminases. ACS sustainable chemistry & engineering, 9(11), pp. 4122-4129. American Chemical Society 10.1021/acssuschemeng.0c09075

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Chiral amines are a common feature of many active
pharmaceutical ingredients. The synthesis of very small chiral
amines is particularly challenging, even via biocatalytic routes, as the
level of discrimination between similarly sized R-groups must be
exceptional, yet their synthesis creates attractive building blocks that
may then be used to prepare diverse compounds in further steps.
Herein, the synthesis of one of the smallest chiral amines, 2-
aminobutane, using transaminases, is being investigated. After
screening a panel of mainly wild-type transaminases, two candidates
were identified: an (S)-selective transaminase from Halomonas
elongata (HEwT) and a precommercial (R)-selective transaminase
from Johnson Matthey (*RTA-X43). Notably, a single strategic
point mutation enhanced the enantioselectivity of HEwT from 45
to >99.5% ee. By covalently immobilizing these candidates, both enantiomers of 2-aminobutane were synthesized on a multigram scale, and the feasibility of isolation by distillation without the need for any solvents other than water was demonstrated. The atom economy of the process was calculated to be 56% and the E-factors (including waste generated during enzyme expression and immobilization) were 55 and 48 for the synthesis of (R)-2-aminobutane and (S)-2-aminobutane, respectively.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Paradisi, Francesca

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

2168-0485

Publisher:

American Chemical Society

Language:

English

Submitter:

Francesca Paradisi

Date Deposited:

09 Apr 2021 08:47

Last Modified:

09 Apr 2021 08:56

Publisher DOI:

10.1021/acssuschemeng.0c09075

BORIS DOI:

10.48350/154666

URI:

https://boris.unibe.ch/id/eprint/154666

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