| Dehydroepiandrosterone is an important raw material for the synthesis of steroid drugs. With the dehydroepiandrosterone as the raw material in this paper, several kinds of aldol condensation products were synthesized by means of aldol reactions with different aromatic formaldehydes. These products were used to react with selected aromatic acyl chlorides and aliphatic acyl chlorides to finally obtain our targets—two new series of derivatives. All these esterification products may have broad application prospect in the fields of anti-cancer metastasis and AIDS prevention. The structures of these derivatives were characterized and eventually confirmed by1H NMR,13C NMR, FTIR, UV and MS.In this dissertation synthesis of17β-hydroxy-17α-methyl-2-aza-5α-androstane-3-one was also explored by a synthetic protocol consisting of four steps, namely oxidation, decarboxylation, oximation and Beckmann rearrangement. But only the product from the first step was obtained. Synthesis of17β-hydroxy-17α-methyl-2-aza-5α-androstane-3-one was eventually achieved by another method, namely oxidation of mestanolone with IBX as oxidant.The following research contents are contained in this dissertation:1. A target2,3-seco-17β-hydroxyl-17a-methyl-5a-androstane-2,3-dicarboxylic acid was synthesized from mestanolone after trying different oxidizing conditions. It was found that the dicarboxylic acid could not be obtained because several by-products were formed at90℃by using chromium trioxide and concentrated sulfuric acid as oxidants. However, we discovered that the target product could be achieved by two steps. The2,17β-dihydroxy-17α-methyl-5a-androstane-l-ene-3-one was first achieved under the condition of tertiary butanol, potassium tert-butoxide and oxygen. Subsequently by the reaction of the intermediate with hydrogen peroxide and potassium hydroxide, the target was obtained, avoiding the elimination reaction of the raw material as a tertiary alcohol. The structure of the dicarboxylic acid was confirmed by1H NMR and13C NMR spectrum.2. Reaction conditions for synthesizing17β-hydroxy-17α-methyl-5α-androstane-l-ene-3-one was investigated. Oxidation of mestanolone with two different oxidants, IBX and DDQ, was studied and the advantage of IBX was confirmed by comparison of reaction temperature, reaction time, and the complexity of by-products. Due to the poor solubility of IBX, this dissertation tries to change the solvent constituents and explores their influence. It was found that solvent consisting of fluorobenzene and DMSO could improve reaction rate to some extent. The oxidation reaction using IBX usually took a long time and could not complete even after5days. Therefore, attempt to speed the reaction by microwave was explored, though it almost had no effect.3. A series of aldol condensation products were obtained by the reaction of dehydroepiandrosterone with different aromatic formaldehydes. The structures of the used aromatic formaldehydes had impact on reaction rate and yield. A series of new ester compounds were obtained through esterification of the aldol condensation products with acyl chlorides. The structures of these derivatives were characterized and eventually confirmed by1H NMR,13C NMR, FTIR, UV and MS. |
