Lycojaponicumins A–C, Three Alkaloids with an Unprecedented Skeleton from Lycopodium japonicum

Abstract

Lycojaponicumins A-C (1-3), three trace alkaloids isolated from Lycopodium japonicum, represent a unique heterocyclic skeleton formed by the new linkage C4-C9. Notably, lycojaponicumins A and B (1 and 2) are the first examples of natural products possessing a 5/5/5/5/6 pentacyclic ring system with a 1-aza-7-oxabicyclo[2.2.1]heptane moiety. These structures were elucidated by spectroscopic methods and X-ray diffraction analysis. A plausible biogenetic pathway was proposed.

Carinatines A and B, Lycopodium Alkaloids from Phlegmariurus carinatus

“…At last, the HMBCs from H-3 and H-7 to C-5 combining with the HMBCs of H-2, H-3, H-6, H-7, and H-10 to C-4 ( δ C 62.4) constructed the linkage of C-5 ( δ C 220.5) and C-6 ( δ C 47.0) and the connections of C-3, C-5, C-9, and C-12 through C-4. Therefore, the planar structure of 2 was established as a new C 16 N-type Lycopodium alkaloid with a 5/5/6/6 tetracyclic ring system, the first derivative of lycojaponicumins C [16].

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“…Carinatine A ( 1 ) was a C 16 N 2 -type Lycopodium alkaloid possessing a 5/6/6/6 ring system formed by a new C-4/C-12 bond. Carinatine B ( 2 ), a new C 16 N-type Lycopodium alkaloid with a 5/5/6/6 tetracyclic ring system, was the first derivative of lycojaponicumin C [16]. Herein, we report the isolation and structure elucidation of these isolates (Fig.…”

Divergent and Efficient Syntheses of the Lycopodium Alkaloids (−)‐Lycojaponicumin C, (−)‐8‐Deoxyserratinine, (+)‐Fawcettimine, and (+)‐Fawcettidine

“…The fawcettimine class of Lycopodium alkaloids are a class of structurally unique natural molecules with more than 80 members,1 among which lycojaponicumin C ( 1 ),2 8‐deoxyserratinine ( 2 ),3 fawcettimine ( 3 ),4 and fawcettidine ( 4 )5 are representative ones (Figure 1). In particular, the alkaloid 1 isolated by Yu and co‐workers from the traditional Chinese medicine ( L. japonicum THUNB) possesses biological activity 2. The structures of the alkaloids of the fawcettimine class feature the fused tetracyclic ABCD frameworks including two common AB rings and two differently‐sized CD rings together with highly crowded quaternary stereocenters.…”

“…Our retrosynthetic analysis was illustrated in Scheme . Based on the reported biogenetic pathway,2 the target molecules 1 and 2 – 4 could be derived from 5 and 6 , respectively. According to our hypothesis above, both 5 and 6 would be expected to be assembled from the key advanced 6/5/5 tricyclic intermediate 8 through intramolecular aza‐Wittig reaction and Schmidt N insertion, respectively.…”

Fawcettimine‐Type Lycopodium Alkaloids as a Driving Force for Discoveries in Organic Synthesis

“…So far, more than 300 Lycopodium alkaloids have been identified . As shown in Scheme , the Lycopodium alkaloids present significant biological activities including inhibition of acetylcholinesterase (AchE), cytotoxicity, anti‐HIV, anti‐inflammatory, etc. Of special note, huperzine A ( 1 ) shows promise for the treatment of Alzheimer's disease by inhibiting AChE …”