Chemoenzymatic Approaches to Izidine Alkaloids: An Efficient Total Synthesis of (+)-Absouline and Laburnamine

Liu, Shaonan; Hai, Yang

doi:10.1021/acscatal.3c03917

Cited by 4 publications

(3 citation statements)

References 33 publications

(25 reference statements)

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“…Our focus hence shifted to the recently discovered PLP-dependent cyclase, LolT, involved in the biosynthesis of loline alkaloids . LolT was previously demonstrated by us to catalyze intramolecular Mannich-type reaction (Figure a), and its activity has been harnessed to produce a variety of heterobicyclic α, α-disubstituted amino acids and amino-izidines. , We envision that its native-function renders LolT an ideal candidate for engineering a PLP-dependent enzyme to catalyze direct asymmetric Mannich reactions between free amino acids and enolizable imines.…”

Section: Resultsmentioning

confidence: 99%

Enzymatic Synthesis of Unprotected α,β-Diamino Acids via Direct Asymmetric Mannich Reactions

Liu,

Gao,

Zou

et al. 2024

J. Am. Chem. Soc.

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Diamino acids are important structural motifs and building blocks for numerous bioactive natural products, peptidomimetics, and pharmaceuticals, yet efficient asymmetric synthesis to access these stereoarrays remains a challenge. Herein, we report the development of a pyridoxal 5′-phosphate (PLP)dependent enzyme that is engineered to catalyze stereoselective Mannich-type reactions between free α-amino acids and enolizable cyclic imines. This biocatalyst enabled one-step asymmetric enzymatic synthesis of the unusual pyrrolidine-containing amino acid L-tambroline at gram-scale with high enantio-and diastereocontrol. Furthermore, this enzymatic platform is capable of utilizing a diverse range of α-amino acids as the Mannich donor and various cyclic imines as the acceptor. By coupling with different imine-generating enzymes, we established versatile biocatalytic cascades and demonstrated a general, concise, versatile, and atom-economic approach to access unprotected α,β-diamino acids, including structurally complex α,α-disubstituted α,β-diamino acids with contiguous stereocenters.

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Section: Resultsmentioning

confidence: 99%

Enzymatic Synthesis of Unprotected α,β-Diamino Acids via Direct Asymmetric Mannich Reactions

Liu,

Gao,

Zou

et al. 2024

J. Am. Chem. Soc.

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“…Recent experimental verification by Gao et al demonstrated that LolD can decarboxylate pyrrolizidine α-quaternary amino acid . In a subsequent study, Liu et al demonstrated the substrate versatility of LolD, enabling rapid generation of diverse enantiopure amino-izidine motifs …”

Section: Plp-dependent Decarboxylasesmentioning

confidence: 99%

Decarboxylation in Natural Products Biosynthesis

Nguyen,

Forstater,

McIntosh

2024

JACS Au

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Decarboxylation reactions are frequently found in the biosynthesis of primary and secondary metabolites. Decarboxylase enzymes responsible for these transformations operate via diverse mechanisms and act on a large variety of substrates, making them appealing in terms of biotechnological applications. This Perspective focuses on the occurrence of decarboxylation reactions in natural product biosynthesis and provides a perspective on their applications in biocatalysis for fine chemicals and pharmaceuticals.

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“…The total synthesis of 1-aminopyrrolizidine alkaloids has been reported using a biocatalytic cascade process involving enzymes from the loline biosynthetic pathway. 32 Acid mediated deprotection, stereoselective 5- endo-trig cyclisation by the Mannich cyclase LoIT and a stereoretentive decarboxylation catalysed by LolD, allowed the efficient one-pot synthesis of the 1-aminopyrrolizidine core (Scheme 2). Subsequent acylation yielded natural products such as (+)-absouline and the first asymmetric synthesis of laburnamine.…”

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confidence: 99%