Casuarinines A–J, Lycodine-Type Alkaloids from Lycopodiastrum casuarinoides

Abstract

Ten new lycodine-type alkaloids, named casuarinines A-J (1-10), along with eight known analogues (11-18), were isolated from the whole plant of Lycopodiastrum casuarinoides . The new structures were established by spectroscopic methods and chemical transformations. Casuarinines A-D (1-4) and J (10) are common lycodine alkaloids possessing four connected six-membered rings, while tricyclic casuarinines E-H (5-8) are the piperidine ring cleavage products. In particular, casuarinine I (9) has an unprecedented five-membered tetrahydropyrrole ring instead of the piperidine ring. A plausible biosynthetic pathway to 9 is proposed. Among the compounds reported, casuarinine H (8) exhibited significant neuroprotective effect against hydrogen peroxide (H₂O₂)-induced neuronal cell damage in human neuroblastoma SH-SY5Y cells, while casuarinines C (3) and I (9) showed moderate inhibitory activity against acetylcholinesterase (AChE).

Salicifoxazines A and B, new cytotoxic tetrahydro-1,2-oxazine-containing tryptamine-derived alkaloids from the leaves of Chimonanthus salicifolius

“…Chimonanthus plants are characteristic for yielding tryptamine-derived alkaloids, 2,8 however, there has been so far no report regarding any alkaloids from C. salicifolius. As a continuing research toward the discovery of bioactive alkaloids from higher plants, 2,9 the leaves of the title plant were reinvestigated. Reported herein are the isolation and structure elucidation of two (1, 2) new and six (3-8) known dimeric tryptamine-derived alkaloids, as well as their cytotoxic effects.…”

Phlefargesiine A, a C16N2 Lycopodium alkaloid with an unprecedented [6/7/6/6]-tetracyclic skeleton from Phlegmariurus fargesii

“…The absolute configuration of 1 was finally determined by electronic circular dichroism (ECD) calculation. 6,8,16 The lowest energy conformations of 1 and 12-epi-1 were optimized at the B3PW91-D3/ pcSeg-1 level with the C-PCM solvent model. The optimized structures were then used for the time-dependent density functional theory (TDDFT) calculation.…”

“…4), displaying a positive Cotton effect at 243 nm and a negative one at 320 nm, resembled those of (13R)-a-pyridone-containing alkaloids (e.g., casuarinines A-C). 5 Biosynthetic pathways for the known lycodine-and phlegmarine-type alkaloids have been well-documented. [1][2][3] Herein, the plausible biogenetic pathways of phlefargesiine A (1) featuring an unprecedented [6/7/6/6]-tetracyclic framework are proposed in Scheme 1.…”

“…Phlefargesiine A (1) was evaluated for its inhibitory effect against acetylcholinesterase (AChE), [5][6][7][8] and only weak activity was observed by showing an inhibitory ratio of 36.2% at 40 lM. Huperzine A (inhibitory ratio of 56.86% at 0.17 lM) was used as the positive control.…”

“…Huperzine A (inhibitory ratio of 56.86% at 0.17 lM) was used as the positive control. 5,7 In addition, the neuroprotective effects of 1 against H 2 O 2 -, oxygen glucose deprivation (OGD)-, and b-amyloid 25-35 (Ab 25-35 )-induced cell damage in human SH-SY5Y neuroblastoma cells 5 were also tested, but no activity was found.…”