Photooxygenation of Furylalkylamines: Easy Access to Pyrrolizidine and Indolizidine Scaffolds

Kalaitzakis, Dimitris; Triantafyllakis, Myron; Sofiadis, Manolis; Noutsias, Dimitris; Vassilikogiannakis, Georgios

doi:10.1002/ange.201600988

Angewandte Chemie

2016

DOI: 10.1002/ange.201600988

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Photooxygenation of Furylalkylamines: Easy Access to Pyrrolizidine and Indolizidine Scaffolds

Dimitris Kalaitzakis

Myron Triantafyllakis

Manolis Sofiadis

et al.

Abstract: Ahighly adaptable method targeting the ubiquitous and very important pyrrolizidine and indolizidine scaffolds is presented. The general synthetic utility of the method is underscored by its application to the rapid and easy synthesis of five natural products starting from readily accessible alkylfuran precursors.T hese unprotected primary furylalkylamines are subjected to photooxygenation conditions,w hich initiate ac omplex cascade reaction sequence concluding with the production of high value motifs.T his se… Show more

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Cited by 14 publications

(1 citation statement)

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“…1A). Motivated by the observation, many groups have developed approaches to expand the chemical space of this family of alkaloids with an intention of hitting more prominent molecules (5,(8)(9)(10). Meanwhile, the diversity landscape of natural polyketide alkaloids suggests the biosynthetic versatility by the species belonging to different kingdoms (3,4,11).…”

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confidence: 99%

Pyridoxal-5′-phosphate–dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi

Dai

Han

Mei

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Indolizidine alkaloids such as anticancer drugs vinblastine and vincristine are exceptionally attractive due to their widespread occurrence, prominent bioactivity, complex structure, and sophisticated involvement in the chemical defense for the producing organisms. However, the versatility of the indolizidine alkaloid biosynthesis remains incompletely addressed since the knowledge about such biosynthetic machineries is only limited to several representatives. Herein, we describe the biosynthetic gene cluster (BGC) for the biosynthesis of curvulamine, a skeletally unprecedented antibacterial indolizidine alkaloid from Curvularia sp. IFB-Z10. The molecular architecture of curvulamine results from the functional collaboration of a highly reducing polyketide synthase (CuaA), a pyridoxal-5′-phosphate (PLP)-dependent aminotransferase (CuaB), an NADPH-dependent dehydrogenase (CuaC), and a FAD-dependent monooxygenase (CuaD), with its transportation and abundance regulated by a major facilitator superfamily permease (CuaE) and a Zn(II)Cys6 transcription factor (CuaF), respectively. In contrast to expectations, CuaB is bifunctional and capable of catalyzing the Claisen condensation to form a new C–C bond and the α-hydroxylation of the alanine moiety in exposure to dioxygen. Inspired and guided by the distinct function of CuaB, our genome mining effort discovers bipolamines A−I (bipolamine G is more antibacterial than curvulamine), which represent a collection of previously undescribed polyketide alkaloids from a silent BGC in Bipolaris maydis ATCC48331. The work provides insight into nature’s arsenal for the indolizidine-coined skeletal formation and adds evidence in support of the functional versatility of PLP-dependent enzymes in fungi.

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mentioning

confidence: 99%

Pyridoxal-5′-phosphate–dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi

Dai

Han

Mei

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Synthesis of Saturated N‐Heterocycles via a Catalytic Hydrogenation Cascade

et al. 2022

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Regioselective Nitrosocarbonyl Aldol Reaction of Deconjugated Butyrolactams: Synthesis of γ‐Heterosubstituted α,β‐Unsaturated γ‐Lactams

2021

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The nitrosocarbonyl aldol reaction of deconjugated butyrolactams is developed employing quinidine as organocatalyst. The nitrosocarbonyl species generated in situ from hydroxamic acids react with a variety of deconjugated butyrolactams at room temperature, offering valuable α,β-unsaturated γ-lactams bearing heterosubstituted quaternary carbon center in very high yields. This nitrosocarbonyl aldol reaction is O-selective and proceeds exclusively at the γ-center of deconjugated butyrolactams. The reaction is scalable, accommodates diverse functional groups, and is also effective with azodicarboxylates.γ-Lactams and derivatives thereof, particularly those encompass unsaturation in the ring framework and quaternary carbon center at the γ-position, constitute an important class of heterocycles with eminence in medicinal and pharmaceutical chemistry. [1,2] They represent the core structure of many natural products and biologically significant molecules (Figure 1). [2] They are also widely used as versatile building blocks in organic synthesis towards complex targets. [3] Consequently, devising straightforward strategies to access functionally rich unsaturated γ-lactams remains in the limelight of organic synthesis. [4] In this scenario, among the diverse synthetic endeavours, exploration of nucleophilic reactivity of γ-monosubstituted deconjugated butyrolactams have fetched considerable impetus as they are accessible in diverse substitution patterns from readily available precursors. [5] However, this strategy results in dienolate intermediate which could react with electrophile either through the αor γ-position, leading to a mixture of regioisomeric products (Scheme 1a). Further, such reactivity of deconjugated butyrolactams has majorly been investigated for carbon-carbon bond forming reactions and exploration in carbon-heteroatom bond forming reactions are scarce. In 2017, Mukherjee et al. reported sulfenylation and selenylation of γ-monosubstituted deconjugated butyrolac-[a

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Photooxygenation of Furylalkylamines: Easy Access to Pyrrolizidine and Indolizidine Scaffolds

Cited by 14 publications

References 51 publications

Pyridoxal-5′-phosphate–dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi

Pyridoxal-5′-phosphate–dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi

Synthesis of Saturated N‐Heterocycles via a Catalytic Hydrogenation Cascade

Regioselective Nitrosocarbonyl Aldol Reaction of Deconjugated Butyrolactams: Synthesis of γ‐Heterosubstituted α,β‐Unsaturated γ‐Lactams

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