Rubriflordilactones A and B, Two Novel Bisnortriterpenoids from Schisandra rubriflora and Their Biological Activities

Abstract

Rubriflordilactones A (1) and B (2), two novel highly unsaturated rearranged bisnortriterpenoids possessing a biosynthetically modified aromatic D-ring, were isolated from the leaves and stems of Schisandra rubriflora. Their structures were established on the basis of extensive spectroscopic methods, including two-dimensional NMR techniques, and confirmed by X-ray crystallographic analysis. Compound 1 showed weak anti-HIV-1 activity, and compound 2 exhibited an EC50 value of 9.75 microg/mL (SI=12.39) against HIV-1 replication with low cytotoxicity.

Total Synthesis of Rubriflordilactone A

“…Thes pectroscopic data for the synthetic rubriflordilactone Awere found to be identical to those for the natural product, with the exception of the specific rotation, which showed an equal and opposite value, thus indicating that 1 is the unnatural enantiomer ( a ½ .1 (c = 0.114, MeOH)). [5,26] In conclusion, we have developed two synthetic strategies that achieve enantioselective syntheses of rubriflordilactone A. These employ palladium or cobalt catalysis to assemble the ABCDE ring system as the key frameworkconstruction step.T he routes are strategically highly convergent because their common late-stage intermediate is just four steps from the end of the synthesis.T he modular nature of the coupling between af unctionalized diyne and AB-ring aldehydes to assemble the cyclization substrates enables aunified approach to other members of this fascinating family of natural products,and offers ahigh degree of flexibility for the synthesis of rubriflordilactone analogues.…”

“…[2] This landmark achievement has recently been complemented by an elegant asymmetric synthesis of rubriflordilactone A( 1,S cheme 1) by Li et al,w here a6 pelectrocyclization was used to assemble the challenging pentasubstituted D-ring arene; [3] and syntheses of the related family members schilancitrilactones Ba nd C, and propindilactone G. [4] Herein, we describe two convergent enantioselective total syntheses of rubriflordilactone A, [5] which are distinct from previous work in that the CDE ring system at the heart of the natural product framework is formed in asingle tricyclization step. [6,7] Thetwo syntheses differ in the method used to construct this CDE framework, which is achieved under either palladium or cobalt catalysis;t he products of these key cyclizations converge on ac ommon late-stage intermediate.…”

Inhibition of cell proliferation in gastric cancer cell lines on exposure to rubriflordilactone A

“…It exhibits promising anti-HIV activity and antitumor activity (Xiao et al, 2006). In the present study, the effect of rubriflordilactone A on the viability and induction of apoptosis in the gastric cancer cells is for the first time investigated.…”

“…Rubriflordilactones A (Figure 1) from isolated from the Schisandra rubriflora that has been widely used in Chinese herbal medicine (Xiao et al, 2006). It exhibits promising anti-HIV activity and antitumor activity (Xiao et al, 2006).…”

Totalsynthese von (+)‐Rubriflordilacton A

“…[4] Hier präsentieren wir zwei konvergente enantioselektive Totalsynthesen von Rubriflordilacton A, [5] bei denen im Unterschied zu bisherigen Studien das CDE-Ringsystem in einer einzigen Tr icyclisierungsstufe gebildet wird. [6, 7] Die beiden Synthesen unterscheiden sich in der Methode,mithilfe derer das CDE-Gerüst aufgebaut wird: entweder durch Palladium-oder durch Cobalt-Katalyse.D ie Produkte dieser Schlüsselschritte werden darauffolgend zu einem gemeinsamen Intermediat umgesetzt.…”