Lepadins

Perhydropyrido[l,2-A][l,2]oxazines are applied as key intermediates in a stereospecific total syntheses of (-)-pumiliotoxin C and 5-e/ /-pumiliotoxin C(96JCS(P1)1113), and the marine alkaloid)—)-lepadins A, B, C (OOOL2955). (2-Pyridyl)propionic acids 13 can be regioselectively prepared via 2,3,4, 4fl,7,8-hexahydropyrido[l,2-A][l,2]oxazin-2-ones 12 (00OL4007). 

Synthesis of Heterocyclic Natural Products (-)-Ephedradine A, (-)-a-Tocopherol, (-)-Lepadin D, and (-)-Phenserine... 

Lactacystin synthesis 196 Lasubine synthesis 134 Lepadin synthesis 142... 

A stereospecific route to enantiopure all-cis-2,3,6-trisubstituted piperidines relies on a cyclization step that is dependent upon temperature, and choice and quantity of base (Scheme 42) <2003TL3963>. Further intramolecular alkylation reactions reported include that of the chiral enaminone to the bicylic structure 35, a key intermediate toward the synthesis of lepadin alkaloids (Equation 80) <2004AGE4222>. 

Kibayashi and coworkers described the stannane-mediated reduction of xanthate (70) in their work towards the preparation the marine alkaloid (—)-lepadin B (equation 42)272, while Danishefsky and his associates provide an elegant, fully synthetic route to the neurotrophic tricycloilliconone (71) involving the reduction of xanthate (72) (equation 43)277. 

A number of a, a -disubstituted 3-piperidinol alkaloids have been found in Cassia or Prosopis species,[1] and, quite recently, alkaloids including this structural unit have also been isolated from ascidian.[2] Many of these alkaloids showed interesting pharmacological activities such as anesthetic, analgestic, and antibiotic activities. Clavepictines A and B, and pictamine, isolated from tunicate, by Cardellina, II[3] or Faulkner[4] and co-workers, possess 3-piperidinol structure. Lepadins A, B, and C, isolated from tunicate, by Steffan[5] and Andersen[6] and coworkers, also have this structural unit. We designed lactam 1 as a useful... 

On the other hand, Steffan isolated lepadin B from the tunicate Clavelina lepadiformis, and, four years later, Andersen and co-workers isolated lepadin B, and C along with lepadin A from the same tunicate. Professor Andersen also reported lepadin A and B showed significant cytotoxic activity toward a variety of murine and human cancer cell lines. The absolute stereochemistry of these alkaloids was also unknown. 

Here, we achieved the first enantioselective total synthesis of clavepictines A and B, pictamine, and lepadin B starting from the... 

Kibayashi s group also completed the total synthesis of lepadins A, B, and C[20]. 

We are grateful to Dr. John H. Cardellina, II, National Cancer Institute, Prof. D. John Faulkner, University of California, San Diego, and Prof. Raymond J. Andersen, University of British Columbia, for kindly providing us with H, l3C NMR spectra of natural clavepictines A, B, Pictamine, and lepadin B. We are also indebted to Dr. Thomas F. Spande, National Institute of Health, for measurement of the GC analysis of synthetic, racemic, and natural quinolizidine 2071 with (3-dextrin chiral column, and to Prof. Andre Rassat, Ecole Normale Superieure, for kindly providing us with racemic quinolizidine 2071. 

Ozawa, T., Aoyagi, S., Kibayashi, C. Totai Synthesis of the Marine Aikaioids (-)-Lepadins A, B, and C Based on Stereocontrolled intramoiecuiar Acyinitroso-Dieis-Aider Reaction. J. Org. Chem. 2001, 66, 3338-3347. 

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