Toward the design, synthesis and evaluation of Protein Kinase C inhibitors

Protein Kinase C (PKC) represents an important regulatory element in the signal transduction pathways of mammalian cells. Research interest has increased enormously since the discovery that PKC plays critical roles in cell differentiation, tumor promotion, oncogenesis and cell regulatory processes. The primary driving force of this project was the study and development of enantioselective PKC inhibitors. To accomplish this objective the four stereoisomers, (2S/4S)-, (2RI4S)-, (2R14R)-, and (2S/4R)-6-N,N-dimethyl-2-methyl-2-oxo-l,3-dioxa- 4-pentadecyl-6-aza-2-phosphacyclooctane bromides (la-d) were synthesized and evaluated. Long-alkyl chain optically pure epoxides, the key intermediates for the synthesis, were prepared from relatively inexpensive glyceraldehyde surrogates. Several other intermediates exhibited other biological responses including spermicidal, anti-HIV, mycobactericidal, and anti-cancer activities.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Department dc:contributor.department

Chemistry

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

1996

Author dc:creator

• Hubieki, Marina Patricia

Chair dc:contributor.committeechair

• Gandour, Richard D.

Committee members dc:contributor.committeemember

• Hudlicky, Tomas
• Brewer, Karen J.
• Castagnoli, Neal Jr.
• Tanko, James M.

• regulatory elements

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

etd-11102005-141121

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/40315