Synthesis And Biological Evaluation Of Some Methyl Substituted Steroidal Derivatives

This thesis includes two parts.1. Design and synthesis of a series of3-methoxy-15-beta-methyl-estrogen glycoconjugates and their evaluation on gastric cancer cell line MGC-803.2. Design and synthesis of a series of3α-or7a-methy-diosgenin derivatives and their evaluation on PTP1B.1. Design and synthesis of a series of3-methoxy-15-beta-methyl-estrogen glycoconjugates and their evaluation on gastric cancer cell line MGC-803.a. The synthetic method for3-methoxy-15-beta-methyl-estrogen was optimized in the total yield of38%with estrone as the starting material. The reaction conditions were mild and the reagents were commercially obtainable, compared with reported methods.b. By evalution of a series of synthetic3-methoxy-15-beta-methyl-estrogen glycoconjugates on gastric cancer cell line MGC-803, we found that the inhibitory activity of glycoconjugates was significantly improved while compared to the lead compound3-methoxy-15-beta-methyl-estrogen.2. Design and synthesis of a series of3a-or7a-methy-methy-diosgenin derivatives and their evaluation on PTP1B.a. We synthesized the compounds D-1, D-2and D-3by introducing of3a-methy or7a-methy to diosgenin. The biological evaluation showed that diosgenin had no obvious inhibition on PTP1B, while D-1, D-2and D-3had moderate PTP1B inhibitory activity.b. We synthesized a series of3a-methy diosgenin derivatives, based on D-1and D-2. The biological evaluation on PTP1B showed:a) the inhibition was improved as the carbonyl of3α-methy diosgenin derivatives was reduction to hydroxyl group (D-1vs E-3, D-2vs E-1); b) The inhibitory activity was improved dramatically as the acetoxy and oxime was introduced to C-7position of3a-methy diosgenin derivatives; c) the inhibition was decreased dramatically as the double bond of A or B ring of3a-methy diosgenin derivatives was reduction to single bond.