Lycopodium alkaloids serratinine

Based on their unique structures and complicated ring skeletons, the Lycopodium alkaloids have attracted sustained attention from the synthetic community [2e, 17]. Our synthesis of serratezomine A (1) [18] currently stands alone, but the structural similarity between serratezomine A and serratinine (4) compels a discussion of prior work towards the latter. This includes syntheses of the framework [19] of serratinine (4) or similar molecules and one total synthesis [20]. 

Katakawa K, Kitajima M, Aimi N, Seki H, Yamaguchi K, Furihata K, Harayama T, Takayama H (2005) Structure elucidation and synthesis of lycoposerramine-B, a novel oxime-containing Lycopodium alkaloid from Lycopodium serratum Thunb. J Org Chem 70 658-663 Inubushi Y, Ishii H, Yasui B, Hashimoto M, Harayama T (1966) Serratinine a novel skeletal Lycopodium alkaloid. Tetrahedron Lett 7 1537-1549... 

Inubushi Y, Ishii H, Yasui B, Hashimoto M, Harayama T (1968) Serratinine a novel skeletal Lycopodium alkaloid. Chem Pharm Bull 16 82-91... 

Harayama T, Ohtani M, Oki M, Inubushi Y (1975) Total synthesis of the Lycopodium alkaloid dl-serratinine. Chem Pharm Bull 23 1511-1515... 

The degradation studies have accounted for all but two carbon atoms and have established the size of all but one ring. Two structural formulas, CXVII-A and CXXVII, are in accord with the properties and the reactions of serratinine. Structure CXVII-A was favored by Inubushi et al. on mass spectrometric grounds. The fragmentation pattern of CXVII-B and diacetyl- CXVIII are explained more readily if one adopts structure CXVII-A. Structure CXVII-A also has in its favor that it may be formally derived by rearrangement of Lycopodium alkaloids of known structure. 

The structures of all Lycopodium alkaloids isolated thus far may be accommodated within the polyacetate biogenetic hypothesis proposed by Conroy 27) which has been alluded to in earlier sections of this review. His scheme proposes that the alkaloids are formed from two 3,5,7-triketooctanoic acid chains. The manner in which the two chains combine is illustrated by the numbering system proposed b " Wiesner (26) and adopted in this review. The odd-numbered C atoms represent the acetate carboxyl and the even-numbered C atoms the acetate methyl groups. This biogenetic scheme was put forward at a time when the structures of only a few alkaloids were known annotinine, lycopodine, a- and j8-obscurine, and selagine. It is perhaps more than coincidental that it also accommodates the novel structural types found in cernuine and serratinine. 

Lycopodium alkaloids are a class of natural products with unique ring systems, which have attracted great interest from a biogenetic point of view. These unique skeletons have prompted extensive phytochemical work and a project was initiated on the alkaloids of the club moss Lycopodium serratum var. serratum. Three new alkaloids, serratezomines A (40), B (41), and C (42), with a seco-serratinine-type, a serratinine-t)q)e, and a lycodoline-t5rpe skeleton, respectively, were isolated from the club moss L. serratum var. serratum (35). All of the structures are listed in Table I. 

Details of the structural elucidation of two unusual alkaloids, serratinidine (6) from Lycopodium serratum var. serratum f serratum and fawcettidine (10) from L. fawcetti have been reported.2 Following an ingenious proposal for the bio-genetic inter-relationships of the common lycodoline (1), serratinine (2), and serratinidine (3) type structures (Scheme 1), the chemical correlation of the last two alkaloids was achieved as outlined in Scheme 2. The final product (6) was... 

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