One-pot cascade reactions for the synthesis of dinitroalkanes in aqueous buffer

Stewart, Kelsey N.; Hawkins, Kendyll G; Andersen, Campbell M.; Domaille, Dylan W.

doi:10.1039/d2re00403h

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…To this end, we recently showed that bio-aldehydes, generated with alcohol oxidase, can undergo a subsequent 3-step organocatalytic cascade to deliver good yields of 1,3-dinitroalkanes in single-flask conditions. 70 We have extended this methodology to include Pictet-Spengler annulation products from either bacterial or yeast-produced bioaldehydes. 71…”

Section: Biocompatible Upgradingmentioning

confidence: 99%

Whole-Cell and Enzymatic Production of Aldehydes

Hawkins

Domaille

2023

Preprint

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Aldehydes are both versatile intermediates in chemical syntheses and used directly as pharmaceuticals, flavors, and fragrances. However, their synthetic preparation with traditional synthetic chemistry often requires harsh operating conditions and/or toxic metals, including osmium or chromium. To improve the sustainability of aldehyde synthesis, emerging efforts have focused on the production of bio-aldehydes via enzymatic oxidation, reduction, or de novo metabolic pathways. Here, we present a practical guide the different ways to synthesize aldehydes with enzymatic and whole-cell systems with an emphasis on circumventing common challenges, including product isolation and avoiding over-reduction or over-oxidation of the desired aldehyde.

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Section: Biocompatible Upgradingmentioning

confidence: 99%

Whole-Cell and Enzymatic Production of Aldehydes

Hawkins

Domaille

2023

Preprint

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“…15,16 Recently, we extended this idea by coupling biocatalysed alcohol oxidation to a three-step Henry-dehydration-Michael cascade to deliver 1,3-dinitroalkanes. 17 Despite this recent progress, there are a dearth of reactions and guiding principles to adapt synthetic transformations to biocompatible conditions.…”

Section: Introductionmentioning

confidence: 99%

Interfacing Whole Cell Biocatalysis with a Biocompatible Pictet-Spengler Reaction for One-Pot Syntheses of Tetrahydroisoquinolines and Tryptolines

Andersen

Domaille

2023

Preprint

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Biocatalytic processes are highly selective and specific. However, their utility is limited by the comparatively narrow scope of enzyme-catalysed transformations. To expand product scope, we are developing biocompatible processes that combine biocatalytic reactions with chemo-catalysis in single-flask processes. Here, we show that a chemocatalysed Pictet-Spengler annulation can be interfaced with biocatalysed alcohol oxidation. This two-step, one-pot cascade reaction converts tyramine and aliphatic alcohols to tetrahydroquinoline alkaloids in aqueous buffer at mild pH. Tryptamine derivatives are also efficiently converted to tryptolines. Optimization of stoichiometry, pH, reaction time, and whole-cell catalyst deliver the tetrahydroisoquinolines and tryptolines in >90% and >40% isolated yield, respectively, with excellent regioselectivity.

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“…revealed that tyramine is a more effective organocatalyst than lysine for biocompatible aldol condensations [17] . We have also expanded the scope of biocompatible reactions by coupling biocatalysed alcohol oxidation to a three‐step Henry‐dehydration‐Michael cascade to deliver 1,3‐dinitroalkanes [18] . Nevertheless, despite this recent progress, there are a dearth of reactions and guiding principles to adapt synthetic transformations to biocompatible conditions.…”

Section: Introductionmentioning

confidence: 99%

Interfacing Whole Cell Biocatalysis with a Biocompatible Pictet‐Spengler Reaction for One‐Pot Syntheses of Tetrahydroisoquinolines and Tryptolines**

Andersen,

Knudson,

Domaille

2023

ChemBioChem

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Biocatalytic processes are highly selective and specific. However, their utility is limited by the comparatively narrow scope of enzyme‐catalysed transformations. To expand product scope, we are developing biocompatible processes that combine biocatalytic reactions with chemo‐catalysis in single‐flask processes. Here, we show that a chemocatalysed Pictet‐Spengler annulation can be interfaced with biocatalysed alcohol oxidation. This two‐step, one‐pot cascade reaction converts tyramine and aliphatic alcohols to tetrahydroisoquinoline alkaloids in aqueous buffer at mild pH. Tryptamine derivatives are also efficiently converted to tryptolines. Optimization of stoichiometry, pH, reaction time, and whole‐cell catalyst deliver the tetrahydroisoquinolines and tryptolines in >90% and >40% isolated yield, respectively, with excellent regioselectivity.

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One-pot cascade reactions for the synthesis of dinitroalkanes in aqueous buffer

Abstract: Dinitroalkanes are powerful synthetic building blocks because of the versatility of the 1,3-dinitro motif. Here, we show that dinitroalkanes can be synthesized from aliphatic aldehydes in a three-step cascade reaction...

Cited by 3 publications

References 31 publications

Whole-Cell and Enzymatic Production of Aldehydes

Whole-Cell and Enzymatic Production of Aldehydes

Interfacing Whole Cell Biocatalysis with a Biocompatible Pictet-Spengler Reaction for One-Pot Syntheses of Tetrahydroisoquinolines and Tryptolines

Interfacing Whole Cell Biocatalysis with a Biocompatible Pictet‐Spengler Reaction for One‐Pot Syntheses of Tetrahydroisoquinolines and Tryptolines**

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