| In recent years, a variety of steroids with unusual and interesting structures, such as polyhydroxyl sterols, steroidal glucosides, steroidal oximes and sodium sterol sulfates, have been isolated from marine organisms. Many of them have showed interesting biological activities. However, because these compounds’contents are very small in nature we obtain them only by the synthetic methods. Through researching to steroidal compounds, people found that the curative effects of the steroidal compounds can been greatly increased and the adverse effects reduced by the chemical modification of steroidal structure, such as introducing some groups into the side-chain of steroid or leading a O or N atoms into the rings of steroid. Therefore, to investigate relations between the biological activity and the structure of steroids, some steroidal lactams, steroidal oximes and steroidal hydrazones compounds were synthesized in this paper.Using natural and obtainable cholesterol, 7-deoxycholic acid and cholic acid as starting materials, nineteen steroids with different structures were synthesized, including five steroidal hydrazones, six steroidal oximes and thirteen steroidal lactams. The structures of products were identified by IR, 1H NMR and 13C NMR.First, using cholesterol as starting material, 3β-acetoxyl-7-aze-B-homocholest-4-en-6-one (6) were obtained by PCC oxidation, selective reduction, oximation,protection of hydroxy group and Beckmann rearrangement. Then a series of ste-roidal lactams are obtained through the transformation of 3β-acetoxyl group. They are 3β-hydroxyl-7-aze-B-homo-cholest-4-en-6-one (7), 7-aze-B-homo-cholest-4-en-3, 6-dione (8), 3-hydroximino-7-aze-B-homo-cholest-4-en-6-one (9), 7-aze-B-homo-cholest-4-en-6-one-3-semicarbazone (10), 7-aze-B-homo-cholest-4-en-6-one-3-thiosemicarbazone (11).Secondly, using 7-deoxycholic acid as starting material, the hydroxyl and carboxyl in nucleus were transformed into the carbonyl and ester by differentreaction. Methyl 3-aze-A-homo-4,12-dione-7-deoxycholicate (22) were obtainedby oximation and Beckmann rearrangement. Then through the transformation offunctional groups, two new compounds were obtained. They are methyl 12α-hy -droxy-3-aze-A-homo-4-one-7-deoxycholicate (23) and methyl 12-hydroximino-3- aze-A-homo-4-one-7-deoxycholicate (24). In addition, methyl 3-aze-A-homo-4,7,12-trionecholicate (16), methyl 7-hydroximino-3-aze-A-homo-4,12-dionecholicate (17), methyl 3-acetoxyl-12a-aze-C-homo-12-one-7-deoxycholicate (28) and methyl3-hydroxy-12a-aze-C-homo-12-one-7-deoxycholicate (29) were synthesized. Thirdly, based on our research before, six 7-deoxycholic acid methylesters with nitrogen function group have been designed and synthesized. They are methyl 3-hydroximino-12-one-7-deoxycholicate (21), methyl 3, 12-dihydroximino-7-deoxycholicate (31), methyl 3β-hydroxy-12(E)-hydroximino-7-deoxycholicate (30), methyl 3-thiosemicarbazone-12-one-7-deoxycholicate (32), methyl 3,12-dithi-osemicarbazone-7-deoxycholicate (33), methyl 3,12-dihydrazone-7-deoxycholicate (34). In addition, the relationship between the structure and biological activityof these compounds was investigated.In a word, we have prepared a series of steroidal lactams and 7-deoxycholic acid derivatives with nitrogen through the chemical modification of A, B and C ring. By the way, some new methods were adopted in the synthesis of some intermediates. These methods show a lot of excellences, such as gentle reaction, less reaction time and economic reagent. The results of our researches provided some valuable references for the synthesis of these compounds. The biological activity of synthetic compounds needs to be further tested, due to the time and conditions. |
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