Chemical transformation and biological studies of marine sesquiterpene (S)-(+)-curcuphenol and its analogs

Abstract

Chemical transformation studies of the marine sesquiterpene phenol (S)-(+)-curcuphenol (1) isolated from the Jamaican sponges, Didiscus oxeata and Myrmekioderma styx, were accomplished. In order to optimize the activity and better understand the SAR of (S)-(+)-curcuphenol, nineteen semisynthetic analogs were prepared and evaluated for activity against infectious diseases. A number of analogs showed significant activity against Mtb and Leishmania donovani, while showing good to moderate activities in antibacterial and antifungal assays as well as against P. falciparium (D6 clone) and (W2 clone). The analogs a, c, h, and r exhibited Mtb activity with MICs of 24.6, 41.2, 6.90, and 50.5 μM, respectively. Analog f shows enhanced activity against L. donovani with an IC 50 of 0.6 μM and IC 90 of 40 μM respectively.

Marine Sponges: Potential Sources of New Antimicrobial Drugs

“…Some studies adressed chemical transformation of the marine sesquiterpene phenol (S)-(+)-curcuphenol, isolated from the Jamaican sponges Myrmekioderma styx. A number of analogs showed significant activity against L. donovani, among which analog f showed enhanced activity against L. donovani with an IC50 of 0.6 M and an IC90 of 40 M, respectively [89]. Dube and colleagues [178] reported a study on antileishmanial activity of the marine sponge Haliclona exigua.…”

“…The analogs a, c, h, and r exhibited M. tuberculosis activity with MICs of 24.6, 41.2, 6.90, and 50.5 μg/ml, respectively [89]. The meroditerpenes, isojaspic acid, cacospongin D and jaspaquinol have been isolated from a sponge of the genus Cacospongia.…”

“…The ability of this parasite to complete its sporogonic cycle at a temperature as low as 16 ºC, compared with 21 ºC for P. falciparum, has substantially contributed to its success in establishing stable foci of transmission in temperate zones [185]. Since removal of the vector of transmission (the Anopheles mosquito) is almost impossible, new antimalarial [198] (S)-(+)-curcuphenol Sesquiterpene Phenol Myrmekioderma styx L. donovani [89] 1,8a;8b,3a-didehydro-8 -hydroxyptilocaulin and 1,8a;8b,3a-didehydro-8 -hydroxyptilocaulin…”

An Entry to Curcuphenol/Elvirol Core Structures via a retro‐Aldol Reaction

“…Elvirol 3 , which was isolated from the plant Elvira biflora (Compositae), is a structural isomer of curcuphenol whose structure does not obey the isoprene rule [7] [8]. Several synthetic pathways for these compounds have been reported in the literature [9-11]. On the biogenetic origin of bisabolene natural products, a hypothesis suggests that the phenolic sesquiterpenes could be formed by aromatization of its cyclic ketone precursors [12].…”

Palladium-Catalyzed Regioselective 2-Carbethoxyethylation of 1H– Indoles By C-H Activation: One-Step Synthesis of Ethyl 2-(1H-Indol-2-Yl) Acetates

“…Among them, 2-(1H-indol-2-yl)acetic acids constitute a valuable class of building blocks for natural product and natural product analogue syntheses ( Figure 1) [4][5][6][7], combinatorial [8], diversity-oriented syntheses [9,10], and medicinal chemistry [11][12][13][14][15][16][17][18]. In addition, they can serve as highly attractive precursors for various chemical transformations, such as diazomethylation to 1-diazo-3-(2-indolyl)-2-propanone [19] and reduction to 2-(2-hydroxyethyl) indole [20].…”