Exotines A and B, Two Heterodimers of Isopentenyl-Substituted Indole and Coumarin Derivatives from Murraya exotica

Abstract

Exotines A and B (1 and 2), two heterodimers of isopentenyl-substituted indole and coumarin derivatives linked through a new fused heptacyclic ring system, were isolated from the roots of Murraya exotica. Their structures were established by comprehensive NMR and MS spectroscopic data analysis, and the absolute configurations were determined by single-crystal X-ray crystallographic analysis and ECD calculations. Compounds 1 and 2 showed inhibition of nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells with IC50 values of 9.2 and 39.9 μM, respectively.

Highly Diastereo‐ and Enantioselective Synthesis of Cyclohepta[b]indoles by Chiral‐Phosphoric‐Acid‐Catalyzed (4+3) Cycloaddition

“…On the basis of the model proposed by Reid and Goodman, the facial selectivity ( Re face of the indole and Si face of the diene) can be rationalized by the chiral environment provided by the tethering phosphoric acid, as proposed in Scheme . Taking into account the reported conformations of cyclohepta‐1,4‐dienes and that of exotine natural products (solution and solid‐state conformation), we hypothesize that a bent boatlike conformation is adopted in the ring‐closing step to afford the all‐ cis product as the major isomer. In the absence of an R 1 group (products 3 f and 3 g ), facile rotation around the C1−C2 bond would bring the aromatic substituent into a more favorable equatorial position, leading to lower diastereoselectivity (see the Supporting Information).…”

“…The cyclohepta[ b ]indole unit is present in a large number of natural products and pharmaceutical drugs . Examples include exotines A and B isolated from Murraya exotica , actinophyllic acid from the leaves of Alstonia actinophylla , ervitsine from Pandacea boiteau , and a synthetic sirtuin 1 inhibitor (Figure ) . Although their prominence in natural and non‐natural bioactive molecules has stimulated considerable synthetic efforts in this area, the construction of cyclohepta[ b ]indoles in a stereodefined way remains challenging, and very few methods enable the asymmetric formation of such molecules .…”

Natural Products Research in China From 2015 to 2016

“…Two heterodimers of an isopentenyl indole and a coumarin unit by a new fused cycloheptene linker, exotines A ( 309 ) and B ( 310 ), were obtained Murraya exotica roots. Compounds 309 and 310 inhibited the NO production in LPS-induced BV-2 microglial cells with IC 50 values of 9.2 and 39.9 μM (positive control quercetin, 17.4 μM) (Liu et al, 2015a ). One unusual sesterterpenoid ( 311 ) and four new sesquiterpene dimers ( 312 - 315 ) were afforded by Inula britannica .…”

Transient [3,3] Cope rearrangement of 3,3-dicyano-1,5-dienes: computational analysis and 2-step synthesis of arylcycloheptanes

“…Inspired by bioactive aryl-cycloheptanes (Fig. 1) which include terpenes (the frondosins,7 liphagal,8 pharbinilic acid9), resveratrol-derivatives (vitisinol C,10 ampelopsin A11), alkaloids12 (ambiguine,13 actinophyllic acid,14 exotine B15), and marketed drugs (irosustat16) and drug leads (the synthetic SIRT1 inhibitor17) (Scheme 1), we hypothesized that 1,5-dienes A and an allylic electrophile B , could be converted to the aryl-cycloheptane scaffold C over, in theory, a simple procedure involving a Cope rearrangement, deconjugative allylation, and ring-closing metathesis (RCM) (Scheme 1). 6b,c Notably, 1,5-dienes of type A are prepared by a simple and convergent two-step protocol from ketones, malononitrile, and cinnamyl electrophiles: all abundant starting material classes 6 b .…”