.1. Male Sterane 7 Beta-(hydroxymethyl) Stereoselective Introduction Of The Study. Samarium Diiodide-mediated 7 Substituted Androstane -5 - Derivatives Synthesis,

The thesis is consisted of two parts as following.1. Stereoselective introduction of 7β-hydroxymethyl unit into androst-5-ene.Stereoselective synthesis of a 7β-hydroxymethyl substituent in steroids wasrarely reported. We suppose that the 7β-hydroxymethyl unit, if it is induced byRfSO2F, can be converted into 6β,7β-cyclopropane unit under tandem homoallylicalcohol rearragement. Androstanes which have the 6β,7β-cyclopropane unit in theirmolecules often exibit important biological activities. For example, Drospirenone,which has the 6β,7β-cyclopropane unit in its structure, has been developded as anovel oral contraceptive drug.Chloromethyldimethylisopropoxysilane was converted into the correspondingGrignard reagent 20. The addition of 20 to the 7-carbonyl group of 32c gave, afteroxidative cleavage of the corresponding carbon-silicon bond of 54,7α-hydromethyl-7β-hydroxyl substituted compound 55, which was stereoselectivelydeoxygenated by means of an ionic hydrogenation to afford 7β-hydromethylsubstituted compound 50. Stereochemical assignment of the 7-substituent incompound 50 was made on the basis of NMR using ROESY experiments. In addition,we have designed a novel route to determine the structural assignments of the7-substituent in compound 54 and 55.This method will make 7β-hydromethyl substituted steroids more easilyobtainable than before. Otherwise, this method will also provide the foundation forthe stereoselective introduction of the 6β,7β-cyclopropane unit into steroids and thepossibility to develop potent new drugs for clinical use.2. Synthesis of 7-substituted androst-5-ene derivatives promoted by samariumiodide (SmI2).Synthesis of some 7-substituted androst-5-ene derivatives has been carried outby SmI2-mediated Barbier-type or Reformatsky-type coupling reactions on3β,17β-di(tert-butyldimethylsilyloxo)-5-androsten-7-one 32c with different organichalides. The resulting 7α-OH and 7β-OH isomers were separated carefully bycolumn chromatography. Their stereochemical assignments at C-7 have been madeon the basis of 13C NMR studies. Although compound 32c has a α,β-unsaturatedketone unit in its structure, it is suitable for the coupling reactions mediated by SmI2and only the 1,2-addition products of 32c were obtained. This method will make7-substituted derivatives of androstene more widely available than before andprovide the opportunities to study their stucture-activity relationship. Mild conditions,homogeneous reactions and simple operations make this method attractive.