Stereocontrolled semi-syntheses of deguelin and tephrosin

Abstract

We describe stereocontrolled semi-syntheses of deguelin and tephrosin, anti-cancer rotenoids isolated from Tephrosia vogelii.

Stereocontrolled Semisyntheses of Elliptone and 12aβ-Hydroxyelliptone

“…Also described is the preparation of elliptone (5), improving upon the methods of Anzeveno 8 and Singhal 9 in terms of scalability and yield. Dihydroxylation of rotenone (1) followed by oxidative cleavage provided norketone (10), which was susceptible to chemoselective Baeyer-Villiger oxidation with excess Oxone to afford lactol acetate (9). 9 Acid-catalysed elimination according to Singhal's procedure afforded elliptone (5).…”

“…9 A highly diastereoselective Étard-like hydroxylation of elliptone (5) gave 12aβhydroxyelliptone (6), the mechanistic details of which we have discussed previously. 10 With the desired natural products in hand biological investigations are ongoing and the results will be reported in due course. 13 All other solvents and reagents were used as obtained from commercial sources.…”

“…: a) OsO4 (0.4 mol%), NMO, citric acid, acetone: H2O (4:1), rt, 22 h, 92%; b) H5IO6, H2O, rt, 4.5 h, 78%; c) Oxone, MeCN: H2O (10:1), rt, 28 h, 35%; d) PTSA, toluene, 80 o C, 1.5 h, 76%; e) K2Cr2O7, HOAc: H2O (2:1), 60 o C, 0.5 h then rt, 18 h, 63%.The subsequent chemoselective Baeyer-Villiger reaction of the norketone (10) was more challenging. The use of traditional oxidants such as meta-chloroperoxybenzoic acid, 9a peracetic acid, and trifluoroperacetic acid, proved unproductive with reactions suffering variously from the norketone(10) or the formation of complex mixtures of unidentifiable polar by-products. More encouraging results were obtained using Oxone, 12 the potassium peroxymonosulfate-containing triple salt, which afforded the mono-oxygenated lactol acetate(9)as the only identifiable product.…”

The in vivo toxicity evaluation of leaf and root methanolic extracts of Tephrosia vogelii Hook.f using animal model

“…Tephrosia vogelii Hook.f. is a medicinal plant used ethnomedically for the treatment of skin infection diseases, scabs, deworming and ectoparasites [10][11][12][13][14][15][16]. It has also been used traditionally in fishing activities and as traditional pesticides in local agricultural activities for many decades [17][18][19].…”

“…The pharmacological study of methanolic extracts of T. vogelii revealed its antimicrobial activities [16,20]. The pharmacological studies on bioactive compounds such as rotenoids and steroids from T. vogelii revealed the potentiality of such compounds for development of pesticides and insecticide [11][12][13][14][15][16][17][18][19]. Although more bioactive compounds are potential antimicrobial agents that could lead to the development of drugs for treating human ailments, the leaves of T. vogelii have been reported to contain bioactive compounds, tephrosin and rotenone, which had exhibited toxicity in fishes [15][16][17][18].…”