This grant will continue development of a major research program to undertake fundamental studies in the chemistry of recently discovered, biologically active antibiotics. The proposed research will investigate preparation of dioxaspiroketal antibiotics which demonstrate a number of valuable biological effects. Examples include: (1) Milbemycin alpha 1; the most potent member of a novel group of macrocyclic lactones with high pesticidal and antihelminthic activity evoked by unprecedented interference of GABA-mediated neurotransmission in invertebrates. (2) Breynolide; the aglycone of the sulfide-containing antibiotic, breynin, demonstrating significant in vivo hypocholesterolemic activity in mammals. (3) Additionally, synthetic approaches will be initiated toward linearol, a hemiketal of the new dolastane family of marine natural products which have displayed antimicrobial and antileukemic activities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017668-07
Application #
3127359
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1980-06-01
Project End
1989-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
7
Fiscal Year
1986
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
47402