The details of the intramolecular 1,3-diyl trapping reactions are being investigated and the results of the investigations are being applied to the total synthesis of natural products. This proposal describes the use of the intramolecular diyl trapping reaction to complete a total synthesis of the very important and potent antiviral and anticancer agent aphidicolin (1). The key steps of the sequence involve (a) a reverse regiochemical mode of addition of a diylophile to a diyl (18 Greater than 19) to first create the CD ring system, including the """"""""troublesome"""""""" pro C9 quaternary carbon, and (b) an intramolecular Diels-Alder reaction (20 Greater than 21) to add rings A and B onto the CD unit. In addition, total syntheses of the anticancer agents diketocoriolin B (2) and hypnophilin (26) are described. The route outlined utilize a regiochemical mode of intramolecular diyl trapping and can be adapted to allow the synthesis of each in chiral form.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA021144-09
Application #
3165473
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1980-12-01
Project End
1986-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Santa Barbara
Department
Type
Schools of Arts and Sciences
DUNS #
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106