Synthesis of Sterically Rigid Cystamine Derivatives.
Abstract
The possibility exists that the cystamine class of radiation protection drugs may be active only in certain conformations. If this should prove to be the cse then cystamine derivatives that are rigidly held in the required conformation may be much more effective radiation protection agents than the freely-rotating cystamine. This investigation has been directed toward the synthesis of bicyclic disulfides that can be converted into sterically rigid cystamine derivatives. The specific synthetic goals of this project are the syntheses of the syn and anti isomers of 8-amino-2,3-dithiabicyclo(3.2.1) octane. Towards this objective a single isomer of 2,3-dithiabicyclo(3-2-1)octan-8-ol was prepared. The synthesis of this alcohol has been improved during the pastyear through the application of high dilution and depolymerization procedures. The stereochemistry of the hydroxyl group in this bicyclic alcohol has been determined to be syn to the disulfide linkage. A potential precursor for the anti isomer has been obtained in the form of trans-2,trans-6-dithioacetylcyclohex-r-l-yl acetate. The preparations of the p-toluenesulfonate and trifluoromethane-sulfonate esters of syn-2,3-dithiabicyclo(3-2-1)octan-8-ol are described. An extensive investigation of the nucleophilic displacement of these esters indicates that they are either inert or that the disulfide linkage cleaves more easily than the desired displacement of the sulfonate ester. (Author)
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 31, 1971
- Accession Number
- AD0732509
Entities
People
- Douglas N. Buchanan
- R. Marshall Wilson
Organizations
- University of Cincinnati