This proposal focuses on the synthesis of antineoplastic agents. In the quassinoid area major emphasis will be placed on completing syntheses of quassimarin, bruceantin, and glaucarubinone. As a result of the lower toxicity in in vivo systems of 4beta-hydroxy withanolide E relative to cardenolides and bufadienolides, a synthetic program centered around 4beta-hydroxy withanolide E has been initiated in an effort to uncover an analog possessing a reasonable therapeutic index. Part III of this proposal focuses on a convergent total synthesis of the potent cytotoxic cyclodepsidpeptide, jaspamide. In addition a number of analogs will be prepared in order to examine the structural requirements for biological activity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA028865-12
Application #
3482131
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1980-06-01
Project End
1993-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
12
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Indiana University Bloomington
Department
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
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