Synthesis of Phosphorus Based Haptens for Monoclonal Catalytic Antibody Production. Phase 2.
Abstract
Our objective in this Phase II project is to synthesize haptens for production of monoclonal antibodies which will catalyse the hydrolysis of phosphorus-based nerve agents. Our syntheses followed three strategies. The first is synthesis of stable pentacoordinate unsymmetrical oxyphosphoranes as haptens for monoclonal catalytic antibodies based on a transition state for phosphonate hydrolysis: 2-(2'- pyridyldithio)propionylamino-2-methyl-3-(S)-(L-(-)-MENTHOXY) (1",3"-DIOXA-4",6 " -DI-TERT-BUTYLBENZO- methyiphosphorane (29) is typical of this approach. In the second approach, the "bait and switch" concept is pursued and methyl 2%(2'-PYRIDYLDITHIO)PROPIONYLAMINOMETHYL-4-(S)-N,N-:dibenzylamino- 2-methyl-3-(S).hydroxypentane)-methylphosphonate (51) and its enantiomer (60), and 2-(3',5'- DINITROBENZOYL)AMINOMETHYL-2-METHYL-3- (S)-hydroxybutane-aminophosphonate (64) are typical of suitable haptens. The third approach is based upon the potential addition of water to the phosphorus atom of a tetracoordinate phosphate to yield an intermediary pentacoordinate system. The typical examples are methyl 2-(p.nitrobenwyl)aminomethyl-2-methyl-3-(S)-(methoxy)(trifluoromethyl)- hydroxybutane phosphonate (69), (2'-pyridyldithio)ethyl diethyl-3 ,3.diiIuoro-3-phosphonopropionic acid ester (70) and diethyl-4,4difluoro-4-phosphonobutyl (2'.pyridyldithio)propionic acid ester (72). The syntheses and structures of various representatives as well as conjugation of 29 with BSA, KLH and PTG are presented in this report.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 22, 1995
- Accession Number
- ADB202797
Entities
People
- Kaiming Liu
- Sudersan T. Tuladhar