Numerous medicinally important compounds are chiral. However, often only one enantiomer of a chiral drug evokes the desired physiological response. Syntheses which provide racemic drugs are wasteful and potentially dangerous. Also, compounds which are chiral by virtue of hydrogen-deuterium substitution, or hydrogen-deuterium-tritium substitution (chrial methyl group), have played important roles in the elucidation of biochemical mechanisms. There is a distinct need for better general methods for the asymmetric synthesis of medicinal agents and isotopically labeled compounds. We propose to investigate the utility of chiral pseudotetrahedral organorhenium complexes (Pi5-C5H5)Re(NO)(PPh3)(X) as chiral auxiliaries in asymmetric organic synthesis. These compounds are easy to synthesize and obtain optically pure. Many reactions have been discovered in which the rhenium-centered chirality is stereospecifically transferred to a new ligand-based chiral center. Through labeling experiments, X-ray crystallography, and MO calculations, we seek to define the mechanistic basis for this asymmetric induction. Among many objectives, we intend to (a) develop new routes to optically active (Pi5-C5H5)Re(NO)(PPh3)(X) complexes; (b) effect 1,2-, 1,3-, 1,4-, and 1,5-asymmetric induction via Diels-Alder reactions of rhenium dienyl and related complexes; (c) effect 1,2-, 1,3-, and 1,4-asymmetric induction via reactions of alkyl ligand carbanions that are Alpha-, Beta-, and Gamma- to the rhenium; (d) develop diastereoselective syntheses and reactions of aldehyde, alkene, and ketone complexes; (e) develop metal-carbon bond cleavage reactions that are stereospecific at carbon; (f) develop enantioselective syntheses of compounds with chiral methyl groups; and (g) develop applications of chiral rhenium complexes in catalysis. From this program of fundamental research, improved syntheses of several types of medicinally important compounds will be realized.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031280-08
Application #
3279241
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1982-07-01
Project End
1991-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Arts and Sciences
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112