Study On The Synthesis Of Several Highly Abundant Deuterium Labeled Steroidal Compounds

Deuterium-labeled steroidal compounds are an important part of isotope labeling research which have very important applications in analytical chemistry,synthetic chemistry,biomedicine,food residue detection and other fields.At present,the sales market of high-abundance deuterium-labeled steroidal compounds is monopolized by foreign reagent companies,and it is still in the initial stage in China.Based on the rare reports of the preparation methods upon high-abundance deuterated steroidal compounds,it is urgent to explore effective synthesis methods.This thesis is divided into two parts:1.Base/acid catalyzed hydrogen-deuterium exchange method was developed using androstenol,testosterone,4-androstene-3,17-dione and progesterone as substrates.KOt Bu,CF₃COOD or DCl were used as catalysts and D₂O was used as a source of deuterium,and the hydrogen-deuterium exchange reactions were carried out under heating conditions to obtain deuterated androsteroids and progesterones.The reaction reduces costs by using solvents（such as 1,4-dioxane,etc.）and D₂O to form a mixed solvent.This method enables efficient and convenient preparation of stable isotope-labeled steroid compounds with abundance greater than 96%.2.Using estrone as substrate,the selective method for synthesis of estradiol with different deuterium-labeled quantities was developed by hydrogen-deuterium exchange using CF₃COOD as a catalyst,D₂O as a source of deuterium.By selection of reaction conditions such as the type and amount of reaction solvent,acid and base,reaction temperature and time,the abundance of the product reaches more than 95%.This method can be applied to other estrogen compounds through substrate extension.The successful synthesis of these compounds fills the gap in this field and also provides a reference for the synthesis of other similar deuterium-labeled drugs.