Marine alkaloids lepadine

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). 

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. 

Toyooka N, Okumura M, Takahata H. Enantioselective total synthesis of the marine alkaloid lepadin B. J. Org. Chem. 1999 64(7) 2182-2183. 

Ozawa T, Aoyagi S, Kibayashi C. Total synthesis of the marine alkaloid (—)-lepadin B. Org. Lett. 2000 2(19) 2955-2958. 

Ozawa, T, Aoyagi, S., and Kibayashi, C. (2001) Total synthesis of the marine alkaloids (-)-lepadine A, B, and C based on stereocontrolled intramolecular acylnitroso Diels-Alder reaction. J. Org. Chem., 66, 3338-3347. 

Lepadins constitute a class of recently discovered antimalarial marine alkaloids. These molecules are decahydroquinoline derivatives bearing a linear eight-carbon chain isolated from two marine invertebrates of Australian origin, Clavelina lepadiformis [49] and Didemnum sp. [50]. 

In 2008, Blechert et al. reported the total synthesis of e/jt-lepadin F (89) and G (90) by a tandem ene-yne-ene RCM [74]. Lepadins are members of marine alkaloids with decahydroquinoline framework. As a key step in their synthesis (Fig. 26) they planned to construct the decahydroquinoline core skeleton by a selective tandem ene-yne-ene RCM of the dienyne precursor (91). Craiceivably, two different reaction pathways could be expected (1) initiation of metathesis may occur at the terminal double bond followed by two consecutive RCMs to afford the desired 6/6 bicycle (92) or (2) initiation may occur on the disubstituted alkene followed by tandem RCMs to produce the undesired 5/7 bicycle (93). Considering the preference of initiation on monosubstituted double bond as well as the directing effect of free hydroxyl group, pathway (1) may be more favored. Gratilyingly, treatment of dienyne (91) with 10 mol% Gmbbs I catalyst smoothly provided the desired 6/6 bicycle (92) in 90% yield. 

Tsuneki H, You Y, Toyooka N, Sasaoka T, Nemoto H, Dani JA, Kimura I. Marine alkaloids (—)-pictamine and (—)-lepadin B block neuronal nicotinic acetylcholine receptors. Biol. Pharm. Bull. 2005 28(4) 611-614. 

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