This proposal focuses on the total synthesis of antineoplastic quassinoids. Specific targets include quasimarin, bruceantin, and glaucarubinone. In addition, we plan to prepare a variety of C(15) esters related to A-norquasimarin in order to examine the structural requirements for biological activity. The hypothesis that membrane cholesterol build up constitutes an early phase in tumorigenesis, led us to concentrate on developing an efficient route to compactin, which has been shown to be a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis. As an extension of earlier studies employing bicyclo[2.2.1]heptane chemistry, we plan to prepare stereospecifically, in optically active form, thienamycin and three C(10) analogs [10Beta-fluoro, 10Beta-methyl, and 10Beta-methoxythienamycin.
| Hunt, K W; Grieco, P A (2000) Baeyer-Villiger oxidation promoted by reaction of peracids with cyclic oxocarbenium ions generated in situ from internal hemiketals. Org Lett 2:1717-9 |
| Grieco, P A; Haddad, J; Pineiro-Nunez, M M et al. (1999) Quassinoids from the twigs and thorns of Castela polyandra. Phytochemistry 50:637-45 |
| Grieco, P A; Haddad, J; Pineiro-Nunez, M M et al. (1999) Non-quassinoid constituents from the twigs and thorns of Castela polyandra. Phytochemistry 51:575-8 |
| Valeriote, F A; Corbett, T H; Grieco, P A et al. (1998) Anticancer activity of glaucarubinone analogues. Oncol Res 10:201-8 |
| Grieco, P A; Vander Roest, J M; Pineiro-Nunez, M M et al. (1995) Polyandrol, a C19 quassinoid from Castela polyandra. Phytochemistry 38:1463-5 |
