Total synthesis of the marine alkaloids (-)-lepadins a, b, and c based on stereocontrolled intramolecular acylnitroso-Diels-Alder reaction.
The first syntheses of (-)-lepadins A and C, as well as a new synthesis of (-)-lepadin B, have been achieved from commercially available (S)-malic acid. The methodology is based on an intramolecular hetero-Diels--Alder reaction of the acylnitroso compound, affording the bicyclic oxazino lactam with trans selectivity, which was converted to the cis-decahydroquinoline via asymmetric enolate hydroxylation followed by intramolecular aldol cyclization. The total syntheses proceed by employing cis-decahydroquinoline bearing the (E)-iodoalkenyl group as the common key intermediate, which underwent a convergent coupling with the (E)-hexenyl unit via a palladium-catalyzed Suzuki cross-coupling reaction for the elaboration of the octadienyl side chain at the C5 position.
Ozawa
T
T
School of Pharmacy, Tokyo University of Pharmacy & Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Aoyagi
S
S
Kibayashi
C
C
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis / Q000737:chemistry; D008386:Marine Biology; D008968:Molecular Conformation; D011804:Quinolines; D012997:Solvents / Q000494:pharmacology; D013237:Stereoisomerism
D000470:Alkaloids; D000970:Antineoplastic Agents; D006574:Heterocyclic Compounds, 2-Ring; D011804:Quinolines; D012997:Solvents; C432305:lepadin A; C414923:lepadin B; C442360:lepadin C