Synthesis And Structures Of New Aromatic Esters Based On 3β-Hydroxy-Pregnadiene-Dione Skeleton

Synthesis and characterization of two series of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton and 5,16-pregnadiene-20-dione skeleton was reviewed.We mainly synthesized the objective compounds through two different derived routes based on the intermediate compound called 16-DPA,which was first synthesized from diosgenin.These compounds may show potential reactivities in the fieds of inhabitor of 5a-reductase,antiandrogenic,antioxidant and lower blood lipid and so on,and could be also used for the biological selection. The structures of the steroids were characterized by 1H-NMR, C-NMR, IR and mass spectrum. Single crystal X-ray diffraction measurement on one of the new compounds, (3β)-(p- methoxybenzoyloxy)-4,16-pregnadiene-6,20-dione revealed that the A, B, C, and D ring adopted half chair, distorted chair, distorted chair, and distorted envelope conformation, respectively. The molecules in the crystal were packed face-to-face at the normal van der Waals distances. This dissertation mainly contains the following aspects:l.We synthesized the intermediate compound 16-DPA by a two-step synthetic sequence: ring-opening reaction and oxidation reaction,using the inexpensive diosgenin as the start material.The reactive temperature,time and N/P(molar ratio) conditions were studied respectively to find the optimal reaction conditions. Experimental results showed that the highest yield was obtained under 10～15℃,5h and 1:1(N/P) conditions.We also find that pulling the result solution of the E-ring-opening reaction into ice-water with stirring can reduce the viscosity of the solid effectively.2. Synthesis and characterization of two series of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton and 5,16-pregnadiene-20-dione skeleton.The target compounds were synthesized by structural modifation of 16-DPA through two different routes.They may be used for the biological selection.The first serial derivatives called aromatic esters based on 4,16-Pregnadiene-6,20-dione skeleton was synthesized via a five-step reaction:epoxidation reaction of double bond,ring-opening reaction,elimination reaction hydrolysis reaction and esterification.We tried two methods for the epoxidation reaction in H2O2/HCOOH and m-CPBA/CHCl3 reaction system respectively. Experimental results showed that it's convenient and with high yield an single stucture in m-CPBA/CHCl3 reaction system.We got high yied respectively when using the anhydrous pyridine in the elimination reaction and extraction instead of filtration in the post-treatment of hydrolysis reaction. Because esterification is essentially a nucleophilic substitution reaction,so the strong electropositive and small stereo-hindrance effect is favorable.The result indicated that the yields of o-furoic acid ester and p- methoxybenzoyloxy ester were higher,77% and 71% respectively, compared to 45% yield of 3,5-dinitrobenzoic acid ester,whose structure includes more substituent groups with strongly absorb-electron effect.The second serial derivatives called aromatic esters based on 5,16-pregnadiene-20-dione skeleton was synthesized via a two-step reaction:hydrolysis reaction and esterification at C3.After compared the two hydrolysis conditions between NaOH/CH30H and KOH/t-BuOH systems,we find that the former need long reaction time but higher yield than the latter,which is coincidence with the mechanism of hydrolysis reaction. The strong basicity of KOH enhances the nucleophilic attack,but the stereo-hindrance effect of t-BuOH decreases the yield.3.Characterization of the serial derivatives.All the first serial products including 10 compounds were characterized by IR spectra,1H NMR spectra,13C NMR spectra and LC-MS,while the second serial ones including 8 compounds were characterized by IR spectra,1H NMR spectra,13C NMR spectra.4.Characterization of (3β)-(p-methoxybenzoyloxy)-4,16-pregnadiene-6,20-dione via single crystal X-ray diffraction measurement.