Total Synthesis of Talatisamine.
Angew Chem Int Ed Engl
; 59(1): 479-486, 2020 01 02.
Article
em En
| MEDLINE
| ID: mdl-31677324
ABSTRACT
Talatisamine (1) is a member of the C19 -diterpenoid alkaloid family, and exhibits K+ channel inhibitory and antiarrhythmic activities. The formidable synthetic challenge that 1 presents is due to its highly oxidized and intricately fused hexacyclic 6/7/5/6/6/5-membered-ring structure (ABCDEF-ring) with 12 contiguous stereocenters. Here we report an efficient synthetic route to 1 by the assembly of two structurally simple fragments, chiral 6/6-membered AE-ring 7 and aromatic 6-membered D-ring 6. AE-ring 7 was constructed from 2-cyclohexenone (8) through fusing an N-ethylpiperidine ring by a double Mannich reaction. After coupling 6 with 7, an oxidative dearomatization/Diels-Alder reaction sequence generated fused pentacycle 4 b. The newly formed 6/6-membered ring system was then stereospecifically reorganized into the 7/5-membered BC-ring of 3 via a Wagner-Meerwein rearrangement. Finally, Hg(OAc)2 induced an oxidative aza-Prins cyclization of 2, thereby forging the remaining 5-membered F-ring. The total synthesis of 1 was thus accomplished by optimizing and orchestrating 33 transformations from 8.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aconitina
/
Aconitum
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article