Synthesis And Anti-microbial Activity Of Chemical Modified Cholesterol And DHEA

Steroids are widely used in the field of medicinal chemistry, and their various bioactivitieshave attracted extensive attentions of many scientists. New researches also indicate thatdehydroepiandrosterone (DHEA) and cholesterol have antimicrobial or anticancer activities.To improve the pharmacological activities, some preliminary chemical modifications to DHEAand cholesterol were carried out following rules of medicinal design.This dissertation contents of four sections as follows: i. The configuration inversion studyon the C-3of3β-DHEA. ii. The epoxidation, polyhydroxylation, lactonization andesterification of DHEA and cholesterol. iii. Chemical modifications of DHEA by introducingC-13side chain. iv. Antimicrobial evaluations of steroid derivatives.1. Using an SN2reaction, the configuration inversion of the C-3of3β-DHEA werecarried out and3α-DHEA acetate were obtained with a total yield of64%. The3α-DHEAacetate and3α-DHEA benzoate were synthesized by an improved “one pot two step”Mitsunobu reaction with a total yield of94%,91%, respectively.2. Twelve5,6-epoxy-3-benzoate/acetate-steriods, Six5,6-diol-3-benzoate/acetate-steriods,five polyhydroxyl6-benzoate-steriods were synthesized.3. Two steriod derivatives with a benzoyloxyl on C-3and a C-13side chain of Taxol onC-6of DHEA and its lactone were designed and synthesized.4. The antimicrobial activities of some target compounds in1and2against Escherichiacoli, Staphylococcus aureus, Bacillus subtilis, Enterobacter aerogenes and Candida albicanswree studied. Five compounds showed moderate inhibitory effection on Staphylococcus aureus,nine compounds inhibit Bacillus subtilis more strongly, and seven compounds showed weakinhibitory effection on Candida albicans.In summary, an efficient synthetic route to configuration inversion of C-3of3β-DHEAwas developed in the thesis,25steriod derivatives were synthesized and15of them showedantimicrobial activites on various levels.