Bifunctional Imine Reductase Cascades for the Synthesis of Saturated -Heterocycles

Overview

Journal ACS Catal

Publisher American Chemical Society

Date 2024 Oct 10

PMID 39386922

Authors

Jeremy I Ramsden

Bruna Zucoloto da Costa

Rachel S Heath

James R Marshall

Sasha R Derrington

Juan Mangas-Sanchez

Sarah L Montgomery

Keith R Mulholland

Sebastian C Cosgrove

Nicholas J Turner

Affiliations

Soon will be listed here.

Abstract

Saturated -heterocycles constitute a vital scaffold for pharmaceutical chemistry but are challenging to access synthetically, particularly asymmetrically. Here, we demonstrate how imine reductases can achieve annulation through tandem inter- and intramolecular reductive amination processes. Imine reductases were used in combination with further enzymes to access unsubstituted, α-substituted, and α,α'-disubstituted -heterocycles from simple starting materials in one pot and under benign conditions. This work shows the remarkable flexibility of these enzymes to have broad activity against numerous substrates derived from singlular starting materials.

Citing Articles

Stereoselective Chemoenzymatic Cascades for the Synthesis of Densely Functionalized Iminosugars.

Swanson C, Gourbeyre L, Ford G, Clapes P, Flitsch S J Am Chem Soc. 2025; 147(7):6067-6075.

PMID: 39925122 PMC: 11848910. DOI: 10.1021/jacs.4c16732.

References

Martin C, Trajkovic M, Fraaije M . Production of Hydroxy Acids: Selective Double Oxidation of Diols by Flavoprotein Alcohol Oxidase. Angew Chem Int Ed Engl. 2020; 59(12):4869-4872. PMC: 7079103. DOI: 10.1002/anie.201914877. View

Cabrero-Antonino J, Adam R, Beller M . Catalytic Reductive N-Alkylations Using CO and Carboxylic Acid Derivatives: Recent Progress and Developments. Angew Chem Int Ed Engl. 2018; 58(37):12820-12838. DOI: 10.1002/anie.201810121. View

Chen W, Ma L, Paul A, Seidel D . Direct α-C-H bond functionalization of unprotected cyclic amines. Nat Chem. 2018; 10(2):165-169. PMC: 5942596. DOI: 10.1038/nchem.2871. View

Yan T, Feringa B, Barta K . Iron catalysed direct alkylation of amines with alcohols. Nat Commun. 2014; 5:5602. DOI: 10.1038/ncomms6602. View

Vitaku E, Smith D, Njardarson J . Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J Med Chem. 2014; 57(24):10257-74. DOI: 10.1021/jm501100b. View

Campos K, Klapars A, Waldman J, Dormer P, Chen C . Enantioselective, palladium-catalyzed alpha-arylation of N-Boc-pyrrolidine. J Am Chem Soc. 2006; 128(11):3538-9. DOI: 10.1021/ja0605265. View

Mangas-Sanchez J, France S, Montgomery S, Aleku G, Man H, Sharma M . Imine reductases (IREDs). Curr Opin Chem Biol. 2016; 37:19-25. DOI: 10.1016/j.cbpa.2016.11.022. View

Kuwano R, Kashiwabara M, Ohsumi M, Kusano H . Catalytic asymmetric hydrogenation of 2,3,5-trisubstituted pyrroles. J Am Chem Soc. 2007; 130(3):808-9. DOI: 10.1021/ja7102422. View

Thorpe T, Marshall J, Harawa V, Ruscoe R, Cuetos A, Finnigan J . Multifunctional biocatalyst for conjugate reduction and reductive amination. Nature. 2022; 604(7904):86-91. DOI: 10.1038/s41586-022-04458-x. View

10.

Zawodny W, Montgomery S, Marshall J, Finnigan J, Turner N, Clayden J . Chemoenzymatic Synthesis of Substituted Azepanes by Sequential Biocatalytic Reduction and Organolithium-Mediated Rearrangement. J Am Chem Soc. 2018; 140(51):17872-17877. DOI: 10.1021/jacs.8b11891. View

11.

Ramsden J, Heath R, Derrington S, Montgomery S, Mangas-Sanchez J, Mulholland K . Biocatalytic N-Alkylation of Amines Using Either Primary Alcohols or Carboxylic Acids via Reductive Aminase Cascades. J Am Chem Soc. 2019; 141(3):1201-1206. DOI: 10.1021/jacs.8b11561. View

12.

Bright J, Byrom D, Danson M, Hough D, Towner P . Cloning, sequencing and expression of the gene encoding glucose dehydrogenase from the thermophilic archaeon Thermoplasma acidophilum. Eur J Biochem. 1993; 211(3):549-54. DOI: 10.1111/j.1432-1033.1993.tb17581.x. View

13.

Irrgang T, Kempe R . 3d-Metal Catalyzed N- and C-Alkylation Reactions via Borrowing Hydrogen or Hydrogen Autotransfer. Chem Rev. 2018; 119(4):2524-2549. DOI: 10.1021/acs.chemrev.8b00306. View

14.

Peschiulli A, Smout V, Storr T, Mitchell E, Elias Z, Herrebout W . Ruthenium-catalyzed α-(hetero)arylation of saturated cyclic amines: reaction scope and mechanism. Chemistry. 2013; 19(31):10378-87. DOI: 10.1002/chem.201204438. View

15.

Savile C, Janey J, Mundorff E, Moore J, Tam S, Jarvis W . Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture. Science. 2010; 329(5989):305-9. DOI: 10.1126/science.1188934. View

16.

Heath R, Birmingham W, Thompson M, Taglieber A, Daviet L, Turner N . An Engineered Alcohol Oxidase for the Oxidation of Primary Alcohols. Chembiochem. 2018; 20(2):276-281. DOI: 10.1002/cbic.201800556. View

17.

Montgomery S, Mangas-Sanchez J, Thompson M, Aleku G, Dominguez B, Turner N . Direct Alkylation of Amines with Primary and Secondary Alcohols through Biocatalytic Hydrogen Borrowing. Angew Chem Int Ed Engl. 2017; 56(35):10491-10494. DOI: 10.1002/anie.201705848. View

18.

Hamid M, Allen C, Lamb G, Maxwell A, Maytum H, Watson A . Ruthenium-catalyzed N-alkylation of amines and sulfonamides using borrowing hydrogen methodology. J Am Chem Soc. 2009; 131(5):1766-74. DOI: 10.1021/ja807323a. View

19.

Wahart A, Staniland J, Miller G, Cosgrove S . Oxidase enzymes as sustainable oxidation catalysts. R Soc Open Sci. 2022; 9(1):211572. PMC: 8753158. DOI: 10.1098/rsos.211572. View

20.

Yang P, Zhang C, Gao W, Ma Y, Wang X, Zhang L . Nickel-catalyzed borrowing hydrogen annulations: access to diversified N-heterocycles. Chem Commun (Camb). 2019; 55(54):7844-7847. DOI: 10.1039/c9cc03975a. View