Total synthesis and stereochemical reassignment of the indole alkaloid vinoxine

Bosch, Joan; Bennasar, M.‐Lluïsa; Zulaica, Ester; Feliz, Miguel

doi:10.1016/0040-4039(84)80023-4

Cited by 14 publications

(4 citation statements)

References 23 publications

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“…Complementary to the work of Wenkert, Bosch, Bennasar, and co-workers independently reported a class of stabilized nucleophiles that incorporated an indole moiety in its structure rather than being tethered to the alkyl substituent of the pyridinium ring. ,,, The first example of this process involved the addition of the anion of methyl 1-indoleacetate to N -alkyl pyridinium salt 104 as the key step in the rapid total synthesis of (±)-vinoxine and (±)-2,7-dihydropleiocarpamine (Scheme ). ,− Moreover, in a revised synthesis of (±)-vinoxine, it was determined that an acetyl group substituent at the C-3 position of the pyridinium salt was optimal for the introduction of the ( E )-ethylene substituent stereoselectively.…”

Section: Nucleophilic Addition To N-alkyl Pyridinium Salts and Their ...mentioning

confidence: 99%

Synthesis of Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselective Addition toN-Activated Pyridines

et al. 2012

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Introduction 2643 2. Nucleophilic Addition of Organometallic Reagents to N-Acyl Pyridinium Salts 2644 2.1. Regioselective Additions to N-Acyl Pyridinium Species and Their Derivatives 2644 2.1.1. Influence of Pyridine Ring Substituents on Regioselectivity of Addition 2646 2.1.2. Control of Regio-and Diastereoselectivity by the Introduction of Removable Blocking Groups 2648 2.2. Synthesis of 4-Pyridones: 1,2-Addition to 4-Methoxypyridines 2649 2.2.1. Diastereoselective Addition to 3-Trialkylsilyl-4-methoxypyridines 2651 2.2.2. Application in the Synthesis of Natural Products Containing Chiral Piperidine Units 2652 2.3. Diastereoselective 1,2-Addition to N-Imidoyl Pyridinium Salts 2652 2.4. Enantioselective 1,2-Addition Controlled by a Chiral Catalyst 2657 2.5. Diastereoselective 1,4-Addition Controlled by Pyridine 3-Substituents 2657 3. Nucleophilic Addition to N-Alkyl Pyridinium Salts and Their Derivatives 2659 3.1. Regioselective Additions to N-Alkyl Pyridinium SaltsNature of the Nucleophile 2659 3.1.1. Organometallic Reagents as Nucleophiles 2659 3.1.2. Cyanide as Nucleophile 2663 3.2. Diastereoselective Additions of Organometallic Reagents to N-Alkyl Pyridinium Salts 2663 3.3. Regioselective Additions of Enolates to N-Alkyl Pyridinium Salts 2666 3.3.1. Wenkert Procedure: Seminal Work 2667 3.3.2. Wenkert Procedure: Addition of Nucleophiles Positioned at the Nitrogen of Indole Derivatives 2670 3.3.3. Wenkert Procedure: Addition of Enolates Located at the C-2/C-3 Position of Indoles 2671 3.3.4. Addition of Miscellaneous Nucleophiles to N-Alkyl Pyridinium Species 2674 4. Nucleophilic Additions to N-Heteroatom Pyridinium Species 2676 4.1. Nucleophilic Additions to Pyridine N-Oxides and N−O Salts 4.1.1. Properties, Synthesis, and Deprotection of Pyridine N-Oxides 4.1.2. Addition of Grignard Reagents to Pyridine N-Oxides 4.1.3. Addition of Cyanide Nucleophiles via Reissert-Type Reactions 4.1.4. Addition of Hetero Nucleophiles to Pyridine N-Oxides and N−O Salts 4.

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Section: Nucleophilic Addition To N-alkyl Pyridinium Salts and Their ...mentioning

confidence: 99%

Synthesis of Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselective Addition toN-Activated Pyridines

et al. 2012

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“…To address the inherent instability of N -alkyl-1,4 dihydropyridines, the enamine was engaged in further bond-forming chemistry in situ, often via tautomerization to an iminium ion and subsequent trapping. Examples of this approach include the synthesis of vinoxine ( 30 ), 28 wherein the coupling of pyridinium salt 32 and enolate 33 is immediately followed by the protonation of the resulting dihydropyridine to induce a Pictet–Spengler cyclization and generate tetracycle 35 by way of iminium ion 34 . Similarly, the azabicyclo[4.3.1]nonane core of ervitsine ( 31 ) 29 was assembled by reacting the dihydropyridine formed from 36 and 37 with Eschenmoser’s salt to form iminium ion 38 which cyclized to 39 .…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of Altemicidin: A Surprise Ending for a Monoterpene Alkaloid

Harmange Magnani,

Hernández-Meléndez,

Tantillo

et al. 2023

JACS Au

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Monoterpene alkaloids encompass distinct chemical diversity and wide-ranging bioactivity. Their compact complexity has made them popular as synthetic targets and has inspired many distinct strategies and tactics in the field of heterocyclic chemistry. This article documents the evolution of a synthetic program aimed at accessing the unusual sulfonamidecontaining natural product altemicidin, which was generally believed to be a monoterpene alkaloid throughout our entire synthetic investigations but has recently been found to originate through an unexpected and quite disparate biosynthetic pathway. By leveraging a pyridine dearomatization/cycloaddition strategy, we developed a concise pathway to the 5,6-fused bicyclic azaindane core and, after significant experimentation, an ultimate synthesis of altemicidin itself. Tactics to productively manipulate the multiple functional groups present on this highly polar scaffold proved challenging but were eventually realized via several carefully orchestrated and chemoselective transformations−investments that paid dividends in the form of significantly shorter chemical synthesis. Surprisingly, the bond-forming logic between our presumed abiotic synthetic strategy to this alkaloid class and its subsequently identified biosynthetic pathway is eerily similar.

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“…The first total synthesis of (±)-vinoxine (38) was reported by Bosch and co-workers in 1984. 56 The strategy in place relied on the formation of the C15-C16 and C2-C3 bonds of the E ring via an annulation reaction between pyridinium salt 107 and indolylacetate 106 (Scheme 28). This approach could also lead to pleiocarpamine (3) via closing of the D ring from (±)-vinoxine (38) through the C6-C7 bond formation.…”

Section: Scheme 26 Total Synthesis Of (±)-16-epi-pleiocarpamine (±)-16-epi-pleiocarpamine-n-oxide (±)-Normavacurine and (±)-Cmavacurinementioning

confidence: 99%