Unified total synthesis of the limonoid alkaloids: Strategies for the de novo synthesis of highly substituted pyridine scaffolds

Schuppe, Alexander W.; Liu, Yannan; Gonzalez-Hurtado, Elsie; Zhao, Yizhou; Jiang, Xuefeng; Ibarraran, Sebastian; Huang, David; Wang, Xiaoyuan; Lee, Jaehoo; Loria, J. Patrick; Dixit, Vishwa Deep; Li, Xin; Newhouse, Timothy R.

doi:10.1016/j.chempr.2022.09.012

“…The second most widely used approach to prepare silyl enols is Mukaiyama-Michael addition. [42][43][44][45] For this purpose, preparation of Michael acceptor 10 was required (Scheme 4). Direct Mannich reaction of the ketone 7 was accompanied with a number of side processes, such as protective group cleavage, hydroxymethylation, etc.…”

Section: Paper Synthesismentioning

confidence: 99%

Examination of Diels–Alder/Tsuji–Trost Route towards Kopsia Alkaloids

Mikhaylov,

Zhigileva,

Molchanova

et al. 2023

Synthesis

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A reaction sequence of Diels-Alder cycloaddition and Tsuji-Trost allylation was examined in terms of its application to synthesis of kopsinine and the related Kopsia alkaloids. Results of the studies in two synthetic directions are presented herein: 1) synthesis of the properly substituted diene, required for the Diels-Alder step; 2) model studies and optimization of the key reaction sequence in the absence of side-chain. Details on the challenging introduction of the side-chain into tetrahydrocarboline ketone and its silylation, resulting in rare but unproductive vinylogous Claisen cyclization, and the successful Mannich/Mukaiyama aldol sequence are disclosed for the first direction. For the second direction endo-selective Diels-Alder reaction with allyl acrylate and Tsuji-Trost allylation providing incorrect stereochemistry are discovered. Interaction of both dienes with an alkyne provides carbazoles via Alder-Rickert reaction.

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“…Over the past decade, we have developed an electrocyclization-aromatization strategy for the synthesis of polycyclic natural products containing densely substituted arenes. [16] Our experience with arene synthesis, [16,17] coupled with inspiring examples from other groups, [18][19][20][21][22][23][24][25][26] suggested an opportunity for the expeditious preparation of this pyridinecontaining molecule through an aza-6π electrocyclization strategy. Herein, we report the first total synthesis of 2 on a gram scale.…”

mentioning

confidence: 99%

Scalable Total Synthesis of Acremolactone B

Ba,

He,

Ren

et al. 2024

Angewandte Chemie

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Acremolactone B is a pyridine‐containing azaphilone‐type polyketide with herbicidal activity. We developed an aza‐6π electrocyclization−aromatization strategy to construct the tetrasubstituted pyridine ring and achieved the first total synthesis of this molecule on a gram scale. A bicyclic intermediate was expeditiously prepared by using [2 + 2] photocycloaddition and chemoselective Baeyer−Villiger oxidation, which was further elaborated to a densely substituted aza‐triene. An electrocyclization−aromatization cascade was exploited to forge the tetracyclic core of the natural product, and the side chain was introduced through diastereoselective acylation and reduction.

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Scalable Total Synthesis of Acremolactone B

Ba,

He,

Ren

et al. 2024

View full text Add to dashboard Cite

Acremolactone B is a pyridine‐containing azaphilone‐type polyketide with herbicidal activity. We developed an aza‐6π electrocyclization−aromatization strategy to construct the tetrasubstituted pyridine ring and achieved the first total synthesis of this molecule on a gram scale. A bicyclic intermediate was expeditiously prepared by using [2 + 2] photocycloaddition and chemoselective Baeyer−Villiger oxidation, which was further elaborated to a densely substituted aza‐triene. An electrocyclization−aromatization cascade was exploited to forge the tetracyclic core of the natural product, and the side chain was introduced through diastereoselective acylation and reduction.

show abstract

Unified total synthesis of the limonoid alkaloids: Strategies for the de novo synthesis of highly substituted pyridine scaffolds

Cited by 5 publications

References 161 publications

Examination of Diels–Alder/Tsuji–Trost Route towards Kopsia Alkaloids

Examination of Diels–Alder/Tsuji–Trost Route towards Kopsia Alkaloids

Scalable Total Synthesis of Acremolactone B

Scalable Total Synthesis of Acremolactone B

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