Marvin J. Núñez

Studies of naturally occurring friedelane triterpenoids as insulin sensitizers in the treatment type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a rapidly expanding public epidemic and frequently results in severe vascular complications. In an attempt to find anti-diabetic agents, we report herein on the isolation, structural elucidation and bioactivity of nine friedelane-type triterpenes (1-9) and twenty two known ones (10-31) from the root barks of Celastrus vulcanicola and Maytenus jelskii. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. Two compounds from this series (1 and 3) exhibited increased insulin-mediated signalling, which suggests these friedelane triterpenes have potential therapeutic use in insulin resistant states.

ent-Rosane and abietane diterpenoids as cancer chemopreventive agents

Two ent-rosane- (cuzcol, 1 and 6-dehydroxycuzcol, 2) and a abietatriene- (salvadoriol, 3) type diterpenoids have been isolated from Maytenus cuzcoina and Crossopetalum uragoga, respectively, along with five known diterpene compounds (4-8). Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, and computational data. The absolute configuration of cuzcol was determined by application of Riguera ester procedure. This is the first instance of isolation of ent-rosane diterpenoids from species of the Celastraceae. The isolated diterpenes were found to be potent anti-tumour-promoter agents, and carnosol (7) also showed a remarkable chemopreventive effect in an in vivo two-stage carcinogenesis model.

Diels–Alder adducts from Celastraceae species

Celastraceae species are a rich source of adducts whose biosynthesis has been hypothesized as involving a Diels–Alder reaction. The co-occurrence of these natural terpenoids adducts with their corresponding precursors, and the reported regio- and stereoisomers support that their biosynthesis may occur via a Diels–Alderase. Triterpene dimers, composed of a quinonemethide and a phenolic nor-triterpene, are the most numerous group of adducts and are all restricted to the Celastraceae family. This review covers natural Diels–Alder adducts from Celastraceae species, providing an overview of the reported terpenoid adducts classified by their monomer nature. In addition, synthetic efforts on the chemical feasibility of the biosynthetic Diels–Alder reactions involved and the biological activities of these metabolites are discussed.

Bioactive diterpenoids from Celastraceae species

Celastraceae species have a long tradition of use in folk medicine and agriculture. Intensive research into this family has resulted in the isolation of a large number of secondary metabolites with a wide range of bioactivity, with the most characteristic being the dihydro-β-agarofuran sesquiterpenes and the quinomethide triterpenoids. Despite diterpenoids not often being found in Celastraceae species, the novelty of their structures and their biological activities has stimulated their research. There are several reviews covering studies on Tripterigium wilfordii, a traditional Chinese medicine, and their metabolites, but none focusing on bioactive diterpenoids isolated from other Celastraceae species. This review focuses on diterpenes isolated from Celastraceae species, and their skeleton diversity, species sources, and tested biological activities are discussed. The literature from January 2000 to October 2016 is reviewed, and 64 references are cited. A total of 118 isolated diterpenoids possessing twelve different skeletons are included and classified by the following tested biological activity: cytotoxicity, anti-inflammatory, antitumour-promotion, anti-HIV, immunosuppressant, reversal multi-drug resistance, and antifeedant. This compliance information will be helpful in further research into diterpene Celastraceae isolation, biological activity determination and structure specific modifications.

Distinct sesquiterpene pyridine alkaloids from in Salvadoran and Peruvian Celastraceae species

As part of a bioprospecting program aimed at the discovery of undescribed natural products from Salvadoran and Peruvian flora, the phytochemical investigations of four Celastraceae species, Celastrus vulcanicola, Maytenus segoviarum, Maytenus jeslkii, and Maytenus cuzcoina, were performed. The current study reports the isolation and structural characterization of five previously undescribed macrolide sesquiterpene pyridine alkaloids, named vulcanicoline-A, cuzcoinine, vulcanicoline-B, jelskiine, and vulcanicoline-C, along with sixteen known alkaloids. The structures of the alkaloids were established by spectrometric and extensive 1D and 2D NMR spectroscopic analysis, including COSY, HSQC, HMBC, and ROESY experiments. The absolute configurations of alkaloids were proposed based on optical rotation sign, and biogenetic considerations. This study represents the first phytochemical analysis of Maytenus segoviarum.