New tigliane diterpenes from Euphorbia grandicornis

Abstract

Phorbol esters are specific acylated polyhydroxy Δ1,6-tigliane diterpenes, which occur in plants of Euphorbiaceae and Thymelaeaceae family. Phorbol derivatives are promising candidates of drug development for HIV therapy, because they reactivate HIV-1 latency by protein kinase C dependent NF-κB activation, and avoid the new infection of CD4+ cells by down-regulating the expression of the HIV 1 receptors [1,2]. Recently we reported the isolation and structure determination of three phorbol analogues from Euphorbia grandicornis Goebel, a succulent cactiform South African plant whose phytochemical investigation has not been reported previously [3]. In continuation of our investigations we report now on the isolation and structural characterization of further six diterpene polyesters. The chloroform-soluble phase of a methanol extract of the fresh aerial parts of E. grandicornis was fractionated by column chromatography on polyamide, then by vacuum liquid chromatography on silica gel. Selected fractions from these separations were further purified by preparative TLC and HPLC to yield six pure compounds, including three new natural products. The structure elucidation was performed by means of HRESIMS and advanced two-dimensional NMR methods, including 1H NMR, JMOD, 1H-1H COSY, NOESY, HSQC, and HMBC experiments. The three known compounds were identified as 12 deoxyphorbol mono- and diesters, acylated with acetic, isobutyric and 2-methylbutyric acids. All of the three new compounds are 12-deoxy-16-hydroxyphorbols; one of them was found to have an unusual parent alcohol with 5-ene-7-ol function.