Serratinine

Inubushi et al. (30) isolated serratinine from L. serratum var. thunbergii and assigned to it the molecular formula, C16H25NO3. In a paper which 

The quaternary nature of C-12 (partial structure B) was deduced from an examination of the NMR-spectrum of CXX V obtained from CXVII-D by oxidation, bromination, and dehydrobromination. The vinyl proton showed a signal of area one at 6.82 8 comprised of two quartets (Ji = 1.8 cps and J2 = 6.2 cps), the hydrogen geminal to the acetoxy group was a doublet of area one at 4.98 S (J = 6.2 cps), and the vinyl methyl signal of area three at 1.88 8 was a doublet (J = 1.8 cps). Irradiation at 6.82 converted the signals at 4.98 8 and 1.88 8 into singlets. From these data it was concluded that C-12 in partial structure B was quaternary. 

The IR-data show ed that the ketone group of serratinine is present in a five-membered ring. Examination of the IR spectra of the ketones deriv ed from the secondary alcohol functions implied that both are present in six-membered or larger rings. This conclusion was confirmed when CXXVI, obtained by dehydration of CXVIII, was treated with diethylacetylene dicarboxylate and gave in one step 4-methyl-phthalate. Cyclohexadienes are reported to react in this fashion. One 

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 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. 

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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]. 

Inubushi s synthesis of racemic serratinine commences with a Diels-Alder reaction of butadiene with substituted quinone derivative 26 (available in four steps from 25,... 

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]... 

In the laboratory of J. Kobayashi, the biomimetic one-pot transformation of serratinine into serratezomine A was accomplished using the Polonovski-Potier reaction Serratinine was first treated with m-chloroperbenzoic acid to obtain the A/-oxide, and then excess TFAA was added. The iminium ion was formed in the following fashion the C13 hydroxyl group formed a hemiacetal with the C5 carbonyl group and simultaneously with the formation of the C5-C13 lactone the C4-C5 bond was broken. The iminium ion was then reduced with sodium cyanoborohydride to afford the tertiary amine functionality. Besides serratezomine A, another lactone (between the C8 hydroxyl and C5 carbonyl) was formed in 27% yield. 

Morita, H., Kobayashi, J. i. A Biomimetic Transformation of Serratinine into Serratezomine A through a Modified Polonovski Reaction. J. 

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... 

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