Steroidal Compound Synthesis And Structural Analysis

Steroids are widely used in the field of medicine.Especially,steroid hormone,including adrenocortical hormone and sex hormone,is a group of drugs of very considerable clinical medical importance.Some steroid drugs are reported having anti-human immunodeficiency virus(anti-HIV) and anticancer activity.At present,the medical field where Steroid drugs are used is becoming more and more widely.For example,they are employed in birth control and treating rheumatism,angiocardiopathy, dermatonosis,alopecia,acne and endocrine dyscrasia and so on.What is more,some of them can accelerate the reproduction and growth of fowl and plants' growth.Up to now,the amount of steroid drugs is only smaller than that of antibiotics all over the world.The main work of this dissertation comprises three parts:1)Dianabol(17α-methyl-17β-hydroxy-androst-1,4-dien-3-one)were characterized by UV,IR,MS,¹H and ¹³C-NMR.In addition,the signal of ¹H and ¹³C-NMR was adscribed,the relation of the signal of IR spectrum and the functional groups was studied,cleavage mechanism of MS was proposed,the TG-DTA of dianabol was also investigated.2)A simple two steps for preparing 4-chloro-testosterone from testosterone undergoing hydrogen peroxide epoxidation and concentrated hydrochloric acid ring-opening reaction with total yield 82.6%was reported.The second reaction was employed with no purification of the obtained product.The reaction had several adventage factors,such as,no pollution,simplicity and high yield and so on.The reaction conditions were optimized.4-Chloro-testosterone was characterized by ¹H-NMR, ¹³C-NMR,IR and MS,cleavage mechanism of MS was proposed.The optimum conditions were,the mole ratio of H₂O₂:NaOH:testosterone and concentrated hydrochloric acid:testosterone were 5:1.24:1 and 1:1 respecticely,the reaction temperature were 0℃and the room temperature, the react time were 20h and 3h in sequence.The purity of the recrystallized crude produce was more than 98.6%.The reaction had good reproducibility.3)A simple synthetic pathway for 4-chloro-Δ¹-17α-methyltestosterone was performed from 4-chloro-17α-methyltestosterone through dehydrogenation by use of 2,3-dichloro-5,6-dicyanobenzoquinone(DDQ)with yield 81.0%without the normol by-product 6-position dehydrogenated ketones.However,It was surprisingly found that the unexpected 4-chloro-17α-methyl-androst-1,4,16-trien-3-one generated from 17-dehydration. The probable mechanism of dehydrogenation was investigated and the reaction conditions were optimized.Products were characterized by ¹H and ¹³C-NMR,IR and MS,cleavage mechanism of MS was proposed.The different major product was obtained in the presence of different acidic catalyst.1,2-Dehydrogenation product 4-chloro-Δ¹-17α-methyltestosterone can be eliminated the 17-OH to introduce double in 16-position obtaining 4-chloro-17α-methyl-androst-1,4,16-trien-3-one in strong acid condition or through prolonging the reaction time or though increasing the reaction temperature.4-Chloro-Δ¹-17α-methyltestosterone was the major product in the presence of p-toluene sulfonic acid(PTS). The conversion of 4-chloro-17α-methyltestosterone and the yield of 4-chloro-Δ¹-17α-methyltestosterone were 94.6%and 81.0%respectively under the optimum conditions:8.90mmol 4-chloro-17α-methyltestosterone was dehydrogenated by DDQ(mole fraction 1.6 to 4-chloro-17α-methyltestosterone) under the catalysis of PTS(mole fraction 1.9%to 4-chloro-17α-methyltestosterone)in benzene(130mL)for 72h at 60℃. The reaction had good reproducibility.