Vlasoulamine A, a Neuroprotective [3.2.2]Cyclazine Sesquiterpene Lactone Dimer from the Roots of Vladimiria souliei

Abstract

Vlasoulamine A (1), an unprecedented sesquiterpene lactone dimer featuring a fully hydrogenated pyrrolo[2,1,5-cd]indolizine core, and vlasoulones A and B (2 and 3), a pair of epimeric dimers formed from a proposed Diels−Alder [4 + 2] cycloaddition between a germacrane sesquiterpene lactone and a eudesmane sesquiterpene, were isolated from the roots of Vladimiria souliei. Their structures and absolute configurations were established by NMR, MS, and single-crystal X-ray spectroscopic analysis. Moreover, 1 exhibited neuroprotective activity when evaluated for glutamate-induced cytotoxicity, nuclear Hoechst 33258 staining, and measuring intracellular reactive oxygen species levels, using a rat pheochromocytoma PC12 cell-based model system.

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

“…[46] It is,t herefore, possible that natural product scaffolds exist in nature which resemble the structures of the new NP-inspired compound classes resulting from our approach thereby further validating it. In agreement with this notion, very recently and while we developed the principle,t he isolation of the natural product vlasoulamine Awas reported, [47] whose scaffold is structurally related to pseudo-sesquiterpenoid alkaloids 36.…”

Natural Nitrogenous Sesquiterpenoids and Their Bioactivity: A Review

“…The ED 50 of compound 377 on the production of NO was 5.73, and obviously inhibited LPS-inducediNOS and COX-2 protein expression in a dose-dependent way, and increased HO-1 protein expression at the concentration of 10 µM [92].Three axane sesquiterpenoid isonitrile pictaisonitrile-1 (378), pictaisonitrile-2 (379), and cavernothiocyanate (380) (Figure 11) were extracted from hyllidiapicta collected from Bali, Indonesia [71]. Vlasoulamine A (381) (Figure 11), an unprecedented guaiane sesquiterpene lactone dimerfeaturing a fully hydrogenated pyrrolo[2,1,5-cd] indolizine core, was isolated from the roots of Vladimiria souliei [93]. Moreover, 381 exhibited neuroprotective activity whenevaluated for glutamate-induced cytotoxicity, nuclear Hoechst 33,258 staining, and measuring intracellular reactive oxygen species levels, using a rat pheochromocytoma PC12 cell-based model system [93].…”

“…Vlasoulamine A (381) (Figure 11), an unprecedented guaiane sesquiterpene lactone dimerfeaturing a fully hydrogenated pyrrolo[2,1,5-cd] indolizine core, was isolated from the roots of Vladimiria souliei [93]. Moreover, 381 exhibited neuroprotective activity whenevaluated for glutamate-induced cytotoxicity, nuclear Hoechst 33,258 staining, and measuring intracellular reactive oxygen species levels, using a rat pheochromocytoma PC12 cell-based model system [93]. Clavukoellians A-D (382-385) (Figure 11), highly rearranged nardosinane Sesquiterpenoids with antiangiogenic activity were purified from the marine soft coral Clavularia koellikeri [94].…”

“…intracellular reactive oxygen species levels, using a rat pheochromocytoma PC12 cell-based model system [93]. Clavukoellians A-D (382-385) (Figure 11), highly rearranged nardosinane Sesquiterpenoids with antiangiogenic activity were purified from the marine soft coral Clavulariakoellikeri [94].…”

Vlasoulides A and B, a pair of neuroprotective C32 dimeric sesquiterpenes with a hexacyclic 5/7/5/5/(5)/7 carbon skeleton from the roots of Vladimiria souliei

“…At the same time, we also have separated some rare dimeric sesquiterpenes exhibiting potential neuroprotection activity from Vladimiria souliei in our previous study. 15,16 Therefore, as a continuing investigation on this plant, two C 32 sesquiterpene dimers, vlasoulides A and B (1 and 2), were isolated from the same plant. Herein, we describe the isolation, structural elucidation and neuroprotective activities of two new compounds (Fig.…”