N-Acyliminium Ion Chemistry: Improving the Access to Unsaturated γ-Lactams and Their N-α-Methoxylated Derivatives: Application to an Expeditive Synthesis of (±)-Crispine A

Souquet, Florence; Drici, Wassila; Fayssal, Sandra Abi; Lazouni, Imane; Thueillon, Sébastien; Pérard-Viret, Joëlle

doi:10.1055/s-0040-1707886

Cited by 3 publications

(2 citation statements)

References 15 publications

(14 reference statements)

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“…We envisioned that N 5 -benzyloxymethyl (BOM) securamine A ( 14 ) might serve as a common precursor to the three distinct isolates shown in Fig. 1A and that 14 could be derived from the isomeric α,β-unsaturated γ-lactam 15 through a cycloisomerization ( 34 , 35 ). The α,β-unsaturated γ-lactam 15 was prepared by means of acid-mediated chlorination and skeletal remodeling of the 12-membered macrolactam 16 , followed by reduction of the nitroarene.…”

Section: Synthetic Strategymentioning

confidence: 99%

An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids

Alexander,

Bartfield,

Gupta

et al. 2024

Science

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Securines and securamines are cytotoxic alkaloids that contain reactive alkene and heterocyclic residues embedded in skeletons comprising four to six oxidized rings. This structural complexity imparts a rich chemistry to the isolates but has impeded synthetic access to the structures in the nearly three decades since their isolation. We present a flexible route to eight isolates that exemplify the three skeletal classes of metabolites. The route proceeds by the modular assembly of the advanced azides 38 and 49 (13 steps, 6 to 10% yield), sequential oxidative photocyclizations, and late-stage functional group manipulations. With this approach, the targets were obtained in 17 to 19 steps, 12 to 13 purifications, and 0.5 to 3.5% overall yield. The structure of an advanced intermediate was elucidated by microcrystal electron diffraction (MicroED) analysis. The route will support structure-function and target identification studies of the securamines.

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Section: Synthetic Strategymentioning

confidence: 99%

An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids

Alexander,

Bartfield,

Gupta

et al. 2024

Science

View full text Add to dashboard Cite

show abstract

“…We envisioned N 5 -BOM securamine A ( 14) might serve as a common precursor to the three distinct isolates shown in Fig. 1f, and that 14 could be derived from the isomeric α,β-unsaturated γ-lactam 15 by a cycloisomerization (34,35). The α,β-unsaturated γ-lactam 15 was prepared by skeletal remodeling of the 12membered macrolactam 16 by treatment with hydrochloric acid, followed by reduction of the nitroarene.…”

mentioning

confidence: 99%

An oxidative photocyclization approach to the synthesis of skeletally-diverse Securiflustra securifrons alkaloids

Alexander,

Bartfield,

Gupta

et al. 2023

Preprint

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Securines and securamines are alkaloids that contain a cis-enamide, neopentylic alkyl chloride, bromoimidazole, and a pyrroloindoline that is in a reversible equilibrium with an indole. More complex isolates contain an oxidized hexacyclic structure, and varied bromination of the indoline that correlates with their cytotoxicity. Here we present a flexible route that provides access to the three skeletally-distinct classes of isolates and which will support elucidation of their structure–function relationships and biological target. The synthesis features the modular assembly of a macrolactam followed by a hydrochlorination cascade that introduces several critical substructures in a single step. The pyrroloindoline and hexacyclic skeletons were assembled by sequential oxidative photocyclizations of a precursor whose structure was elucidated by MicroED analysis, a burgeoning method for structure determination.

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Synthesis of New Isoquinoline Derivatives from the Condensation Products of Acid Anhydrides and 2-(3,4-Dimethoxyphenyl)ethanamine

et al. 2022

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N-Acyliminium Ion Chemistry: Improving the Access to Unsaturated γ-Lactams and Their N-α-Methoxylated Derivatives: Application to an Expeditive Synthesis of (±)-Crispine A

Cited by 3 publications

References 15 publications

An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids

An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids

An oxidative photocyclization approach to the synthesis of skeletally-diverse Securiflustra securifrons alkaloids

Synthesis of New Isoquinoline Derivatives from the Condensation Products of Acid Anhydrides and 2-(3,4-Dimethoxyphenyl)ethanamine

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