Phlegmarine-Type Alkaloids

Phlegmarine-type alkaloids possess a C16N2 skeleton that consists of a piperidine ring and a (decahydro)quinoline ring that are connected via a methylene group (Scheme 10). They might be the biogenetic intermediates of lycodine (49) We next describe the structure elucidation of this new class of alkaloids based on asymmetric total syntheses. 

New alkaloids lycoposerramines-X (74) and -Z (75) are phlegmarine-type alkaloids consisting of a piperidine ring with a novel nitrone residue and a decahydroquino-line ring with four stereogenic centers [43] (Fig. 6). From spectroscopic analyses, 74 and 75 were found to be diastereomers at the C-13 position, but their absolute configuration could not established. Then we planned the asymmetric total syntheses of 74 and 75 to confirm their structures, including the absolute stereochemistry. 

As described above, we have achieved the asymmetric total syntheses of lyco-poserramines-V (50), -W (68), -X (74), and -Z (75) using cyclohexanol 59 as the common intermediate, which has enabled us to determine unambiguously the structures, including the absolute configurations, of the four new phlegmarine-type alkaloids (Fig. 7). 

Shigeyama T, Katakawa K, Kogure N, Kitajima M, Takayama H (2007) Asymmetric total syntheses of two phlegmarine-type alkaloids, lycoposerramines-V and -W, newly isolated from Lycopodium serratum. Org Lett 9 4069 072... 

Katakawa K, Kitajima M, Yamaguchi K, Takayama H (2006) Three new phlegmarine-type Lycopodium alkaloids, lycoposerramines-X, -Y and -Z, having a nitrone residue, from Lycopodium serratum. Heterocycles 69 223-229... 

Lyconadin A (44) is a novel type of alkaloid consisting of five fused rings (one 5-membered and four 6-membered rings), while alkaloid 45 is the first lycodine analog with a hydroxy group at C-11 (37). A plausible biogenetic path for 44 and 45 is shown in Scheme 9 (37). Both alkaloids may be derived from L-lysine via pelletierine, followed by further cyclization of the phlegmarine skeleton (74,77). 

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