1. Effects of a trimethylsilyl substituent on the photochemical rearrangement of 2,5-cyclohexadienones. 2. Development and implementation of novel electron density-derived molecular surface descriptors.

摘要

The first section of the present work details the preparation and photochemistry of 3-trimethylsilyl-2,5-cyclohexadienones; in addition, an acid catalyzed rearrangement to yield 4-alkylidene-cyclopentenones was investigated. The trimethylsilyl group has been found to be a very effective control agent of the photochemistry of 2,5-cyclohexadienones. Noteworthy discoveries include (i) the regiospecificity and high chemical efficiencies for the type A photorearrangements of 3-trimethylsilyl-2,5-cyclohexadienones 42 to give the bicyclohexenones 44, (ii) the generality and high chemical efficiencies for the acid-catalyzed rearrangements of the bicyclohexenones 44 to 4-alkylidene-2.cyclopentenones 47 and (iii) the effect of the 3-trimethylsilyl substituent on the intramolecular 2+2 photocycloaddition of 4-(3′-butenyl)-2,5-cyclohexadienones. The purpose of the next section in this dissertation is to explore two novel electron density-derived descriptor methodologies in the context of QSAR models for a blood-brain barrier data set (Lombardo), a human intestinal absorption data set (HIA) and two sets of HIV reverse transcriptase inhibitors (HIV-1 and HIV-2). The investigation has reduced to practice the WCD and hybrid shape/property methodologies as novel electron density-derived descriptors.{09}The investigation has established the utility of the WCDs and hybrid shape/property descriptors in generating predictive QSAR models for the four data sets listed above. The application of sensitivity analysis as a new method for feature selection in QSAR was also very successful, the Stripminer program outperformed the GA/PLS feature selection algorithm in every case.