One-Carbon Insertion and Polarity Inversion Enabled a Pyrrole Strategy to the Total Syntheses of Pyridine-Containing Lycopodium Alkaloids: Complanadine A and Lycodine

Autor:	Brandon S. Martin, Mingji Dai, Donghui Ma, Katelyn S. Gallagher, Takeru Saito
Rok vydání:	2021
Předmět:	Lycopodium Polarity (international relations) biology Persistent pain chemistry.chemical_element General Chemistry biology.organism_classification Biochemistry Combinatorial chemistry Catalysis chemistry.chemical_compound Colloid and Surface Chemistry chemistry Pyridine Carbon Pyrrole
Zdroj:	Journal of the American Chemical Society. 143:16383-16387
ISSN:	1520-5126 0002-7863
Popis:	Complanadine A and lycodine are representative members of the Lycopodium alkaloids with a characteristic pyridine-containing tetracyclic skeleton. Complanadine A has demonstrated promising neurotrophic activity and potential for persistent pain management. Herein we report a pyrrole strategy enabled by one-carbon insertion and polarity inversion for concise total syntheses of complanadine A and lycodine. The use of a pyrrole as the pyridine precursor allowed the rapid construction of their tetracyclic skeleton via a one-pot Staudinger reduction, amine-ketone condensation, and Mannich-type cyclization. The pyrrole group was then converted to the desired pyridine by the Ciamician-Dennstedt rearrangement via a one-carbon insertion process, which also simultaneously introduced a chloride at C3 for the next C-H arylation. Other key steps include a direct anti-Markovnikov hydroazidation, a Mukaiyama-Michael addition, and a Paal-Knorr pyrrole synthesis. Lycodine and complanadine A were prepared in 8 and 11 steps, respectively, from a readily available known compound.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::1392b9e5a554c730a81a18fa02c92ff6 https://doi.org/10.1021/jacs.1c08626 Zobrazit plný text záznamu