Serratinine structure

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. 

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]. 

The biosynthetic pathway from a lycopodine derivative to serratinine 4 was proposed previously (a) Inubushi Y, Ishii H, Yasui B, Harayama T (1966) Tetrahedron Lett 7 1551 (b) Inubushi Y, Ishii H, Yasui B, Harayama T (1968) Chem Pharm Bull 16 101 (c) the references in (a) and (b) both have the incorrect stereocenter at C4. This was not established unambiguously until a crystal structure of a derivative was obtained see [4c]... 

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... 

The structure of fawcettidine (10) was indicated from the similarity of its i.r. and n.m.r. spectra and basicity to those of serratinine.2 Transformation of a serratinine derivative (7) into fawcettidine was thus envisaged and ultimately achieved by the sequence outlined in Scheme 3. The required intermediate (8) for the reductive rearrangement to (9) and (10) was obtained in four conventional steps. On the basis of previous studies, the alkaloid fawcettimine had been assigned structure (9). Unfortunately, direct comparison of synthetic (9) with the natural product could not be effected. 

Comparison of structures (17) and (1) clearly shows that the former could serve as a biogenetic model for the first step of the lycodoline to serratinine rearrangement (1)— (2). In point of fact, treatment of (17) with acid gave compound (18), thus lending some credence to the proposed biogenetic route.5... 

Preliminary reports 25, 26) leading to the assignment of the structure and stereochemistry of serratinine were reviewed previously (i). Since then this work has been communicated in full detail 27-30) and an X-ray study of a serratinine derivative has been carried out 31). The X-ray study showed that the structural and stereochemical deductions made from chemical and spectroscopic examination were correct except for the assignment of configuration at C-4. The C-3—C-4 bond should be in the position as shown in revised structure 45 for serratinine. 

The ring system of all four of the title alkaloids is similar and was established by correlation with the structure of serratinine. Early... 

Fawcettidine (57, 38) has been shown to have a CHCH3 group, a trisubstituted double bond, and a carbonyl (rmax 1740 cm ) probably in a five-membered ring and it has been shown to be a weak base (pKj = 6.2). It was noted that the spectroscopic properties of 56 and fawcettidine had many features in common and that their basicities were comparable, indicating that fawcettidine might have structure 61 (55, 39). The preparation of 61 from serratinine was therefore attempted. 

For this purpose serratinine was converted by conventional procedures into 62 which was treated with Zn and acetic acid in a manner similar to 55 and with a similar result. Two products were isolated from the reaction, one a carbinolamine assigned structure 63, the other, an anhydro compound 61, that proved to be identical with natural faw-cettidine by comparison of the natural and synthetic picrates. 

The presence of a cyclopentanone with an exocyclic double bond was evident from the IR and the UV spectra of 67. The single vinyl proton of the exocyclic double bond appeared as a quartet at S 6.82 (J = 6 and 1.5 Hz) and is probably adjacent to a methylene. A broad band at 1410 cm in 67 and 68 indicates that there is a methylene adjacent to the ketone function of the cyclopentanone system. The structural features deduced from the spectroscopic studies may be incorporated into the ring system found in fawcettidine as shown in expression 67. This structure was confirmed through catalytic reduction of 0-acetyl-alolycopine to 56 whose preparation from serratinine has already been described. 

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... 

Nishio K, Fujiwara T, Tomita K, Ishii H, Inubushi Y, Harayama T (1969) The crystal structure of 13-acetyl-8-p-bromo-benzoyl serratinine the revised configuration of C4-N bond of serratinine. Tetrahedron Lett 10 861-864... 

The environment about the nitrogen was established through Hofmann degradation of the methiodide of CXVIII. The first methine, formed by cleavage of the N—C—4 bond, was reduced to the dihydromethine. The latter was converted in successive reactions to a nitrogen-free compound, which from its spectral properties, had two vinyl groups. In serratinine, therefore, the structure about nitrogen is represented in Partial Structure C. 

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. 

Figure 22. Molecular structure of serratinine (83) obtained by X-ray analysis (ORTEP drawing ellipsoids are drawn at the 30% probability level). One molecule of MeOH is contained in the crystal and the hydrogen atoms are omitted for clarity 80).

---