RESUMO
An 11-step enantioselective total synthesis of (+)-sieboldine A (1) has been accomplished from (5R)-methylcyclohex-2-en-1-one (16), in which an intramolecular ketone/ester reductive coupling followed by one-pot acidic treatment to quickly construct the unique oxa-spiroacetal and a TsOH-catalyzed displacement to directly form the characteristic N-hydroxyazacyclononane ring successfully served as the key methodologies. Moreover, several full-skeleton analogues of 1 were also synthesized on the basis of the advanced intermediates, and their inhibitory effects on electric eel acetylcholinesterase were examined.
Assuntos
Acetilcolinesterase , Cetonas , Estereoisomerismo , ÉsteresRESUMO
A unified route for the total synthesis of three tetracyclic diquinane Lycopodium alkaloids (+)-paniculatine, (-)-magellanine, and (+)-magellaninone has been accomplished in 13-14 overall steps based on late-stage diverse transformations from an advanced tetracyclic common intermediate. In the established synthesis, quick formation of the two five-membered rings was efficiently achieved by an intramolecular reductive coupling of ketone-carbonyl and ester-carbonyl and an organocatalytic intramolecular Michael addition of aldehyde-derived enamine to an internal enone functionality with satisfactory redox and step economies and excellent stereoselectivities, providing the requisite tricyclic carbo-framework possessing multiple dense stereogenic centers, and an intramolecular reductive amination finally furnished the essential piperidine ring.
Assuntos
Alcaloides , Lycopodium , Compostos Heterocíclicos de 4 ou mais Anéis , Estrutura Molecular , EstereoisomerismoRESUMO
A short, scalable, and collective total synthesis of four fawcettimine-type Lycopodium alkaloids in eight or nine steps is disclosed. A dense multi-small-ring spiro-α-aminocyclopentanone successfully served as the key intermediate, which was directly accessed by a LiDBB-mediated intramolecular reductive coupling of the aliphatic imine and an ester-carbonyl. Compared to those that employ classical Heathcock intermediate(s) containing a nine-membered ring, the new strategy shows the significant improvement of the synthetic step and redox economies as well as excellent stereochemical control.
RESUMO
A new enantioselective total synthesis of phlegmarine-type Lycopodium alkaloid lycoposerramine-Z (1) has been accomplished, using one-pot chemoselective sequential additions of two different Grignard reagents to the bis-Weinreb-amide intermediate and an efficient construction of the fully fuctionalized cyclohexanone intermediate with a chiral phosphoric acid catalyzed enantioselective intramolecular Michael addition.