Characterization Of Mibolerone The Synthesis Process And Its Structure

Mibolerone is a high efficiency and low side-effect assimilation hormone, whose physical constants, spectral properties and synthetic method have not been reported in the literature. In this thesis, procedures for mibolerone, methylnorandrost and 6-dehydrogenation compound of methylnorandrost were investigated. Intermediates and titled compound were characterized by the 1H and 13C nuclear magnetic resonance (NMR) and infrared (IR) and mass spectrum(MS). In addition, cleavage mechanism of mass spectral(MS) was proposed.Two routes for Mibolerone were designed on the basis of referrences. The first pathway was selectively and quantitatively protected the 3-keto group with methanol starting from estr-5(10)-en-3,17-dione, then the 17-keto group attacked by methyllithium forming 17-methyl compound i.e methylnorandrost, and then methylnorandrost dehydrogenated with chloranil introducing double bond in the six position; Finally,the target molecule was afforded through the Michael addition with dimethyl cuprous lithium. Compared to the first route, most part of the second pathway were the same as above the route including preparations for methylnorandrost and target molecule except the procedure for the dehydrogenation product of methylnorandrost, whose method was brominated through NBS, then dehydrohaloenated to form double bond in the six position.Procedure for methylnorandrost was carfully studied. In the traditional procedure, estr-4-ene-3,17-dione was treated with ethyl orthoformate, the yield reaching 42%. However, in the new procedure, the 3-keto group of the estr-5(10)-ene-3,17-dione could be selectively and quantitatively protected with methanol, whose yield could hit 100%. Methanol is abundant and very cheap in the industry. In the meanwhile, the reaction condition is mild and easily operated. During the preparation of methylnorandrost, solvents such as anhydrous ether, anhydrous tetrahydrofuran(THF) and mixture of benzene-anhydrous ether and so oh as reaction systems having effect on the yield were investigated, the yield respectively being 32%, 41.3%, 37%. So the THF was a good reaction solvent for this reaction. In addition, methyl lithium took place of theGrignard reagent to react in the 17-keto group, whose yield improved from 37% to 51%.Preparation of 6-dehydrogenation compound was researched. 6-dehydrogenation reaction of methylnorandrost was employed with chloranil to directly dehydrogenate 7-H to form the double bond, the yield giving 64%. In this reaction, the tert-butyl alcohol, ethyl acetate, tetrahydrofuran etc respectively as solvent systems in the presence of hydrochloric acid were investigated, the yield respectively giving 24%, 56%, 64%. At the same time, the method with NBS to introduce double bond of methylnorandrost in the six position was studied. In the course of experimental, yield on the reaction of 3-keto group selectively protected was very low, just giving 42%. Several by-products were shown by TLC in the brominating reaction, and work-up being difficult.Procedure for titled compound was developed. Michael 1,6 conjugation addition reaction between dimethyl cuprous lithium and 6-dehydrogenation compounds in the solvent of THF directly provided mibolerone, the yield being 50%.The reaction condition was optimized and steps decreased in this route, whose yield was 16.3%. After being further inverstigated, it will be expected to be a commercial procedure.