The synthesis and enantiomer separation of a number of polycyclic ketones

Drugs possessing chiroptical properties have always posed certain problems to both the pharmacologist and the toxicologist in terms of decreased effectiveness or enhanced toxicity of racemates of certain of these agents. Resolution of racemates thus remains an important facet in the whole context of rational guantitative drug design. The objectives of this study was firstly to find a common, chiroptically pure prescursor to a wide range of known, pharmacologically active polycyclic amines related to pentacyclo[5.4.0.0 sup (2,6).0 sup (3,10).0 sup (5.9)] undecane and (D3)-trishomocubane. Secondly it was also within the scope of this study to determine the absolute configuration of this resolved precursor. In this dissertation the synthesis and resolution of oxazolidines derived from two diketones i.e. pentacyclo[5.4.0.0 sup(2,6).0 sup(3,10).0 sup (5,9)] undecane-8,11-dione and 1-methylpentacyclo[5.4.0.0 sup (2,6).0 sup (3,10). 0 sup (5.9)] undecane-8,11-dione were performed using L-ephedrine and L-PSI-ephedrine as diastereomer formers. Resolution was performed by recrystallising the diastereomeric mixtures for methanol. Specific reactions aimed at transformation of the remaining carbonyl group, failed to yield the desired products. Huang-Minlon reduction afforded the hydrocarbon pentacyclo[5.4.0.0 sup (2,6).0 sup (3,10).0 sup (5,9)]undecane, while LiAlH4 not only reduced the carbonyl moiety, but also reductively split the C-O bond of the oxazolidine ring. Resolution could, however, be performed on the methylsubstituted diketone to yield the enantiomer (1R)-methylpentacyclo[5.4.0 sup (2,6).0 sup (3.10).0 sup (5.9]undecane-8,11-dione. The stereochemistry of this enantiomer was confirmed by X-ray crystallography and application of a noval octant rule to the diketone