| The overall dissertation objective was to synthesize various N-benzoyl analogs of enaminones from cyclohexane-1,3-diones in an effort to discover novel antiasthmatic compounds. Traditional methods to such synthons are problematic, thus limiting the potential for applying high throughput synthetic techniques, like parallel synthesis. As a result, we developed a much improved general procedure for the preparation of N-(3-oxocyclohex-1-enyl)benzamides in connection with our ongoing research interest. Described herein are the first base catalyzed N-benzoylation of primary enaminones of cyclohexane-1,3-diones, employing NaH, which provided significantly higher yields (71--79%) for a variety of compounds 7--9 (Figure 2.1.) than reported previously in literature (15--25%). Furthermore, the twelve targeted N-benzoyl vinylogous imides 21--32 (Figure 3.1.) were synthesized, via this novel method, using solution-phase parallel synthesis techniques in (63--90%) yields. Rolipram (35, Figure 5.1.) was needed as an internal standard for the asthma study and therefore was synthesized (35.2%). Existing compounds synthesized were characterized by comparison with the spectroscopic data and/or melting points of compounds previously reported in literature. The novel imides 21--32 were characterized by (1H NMR, 13C NMR and FTIR) spectral analysis and elemental analysis. Finally, three of the targeted imides (22, 29 and 30) were analyzed by X-ray diffraction. The PDE4 bioactivity analyses of imides 21--32 are shortly underway at the Asthma Center in Johns Hopkins University, and therefore will not be discussed. |
