Design And Synthesis Of Anti-tubercular Sterols-parguesterol And Their Analogues

The aim of this dissertation is to efficiently synthesize novel anti-tubercular sterols-parguesterol A and parguesterol B and their analogues.1. Synthesis of parguesterol A and parguesterol BThe target molecules parguesterol A and parguesterol B were synthesized in 11 steps including methyl etherification, p-tolylsulfonyl etherification and SN2-E1, ozonization, intramolecular Aldol reaction, protecting, Grignard isopropylation, methylenation, deprotecting and intramolecular dehydration in the total yield of 29~35% using hyodeoxycholic acid 41 as the starting material, methyl 3β-tert-butydimethylsilyoxyl -5β-hydroxy-6β-dimethoxylmethyl-B-norcholestane 46 as the key intermediate, and Grignard isopropylation as the key step.2. Synthesis of the analogues of parguesterol A and parguesterol B1) 6β-formyl-3β,5β-dihydroxyl-B-norcholestane-24-one 79 andΔ5(6)-6β-formyl-3β-hydroxyl- B-norcholestane-24-one 80 were synthesized in 9~10 steps from hyodeoxycholic acid 41 in the yield of 42 and 35%.2)Δ5(6)-6β-formyl-3β-hydroxyl-B-norcholanic acid 81 and methylΔ5(6)-6β-formyl-3β-hydroxyl-B-norcholestane 82 were respectively synthesized from hyodeoxycholic acid 41 in the yield of 61% and 29% by 6 steps.3) 3β-tert-butydimethylsilyoxyl-5β,24-dihydroxy-6β-dimethoxylmethyl-24-ethyl-B,25 -dinorcholestane 83 and 3β-tert-butydimethylsilyoxyl-5β-hydroxy-6β-dimethoxylmethyl- B,25-dinorcholestane-24-one 84 were respectively synthesiszed from hyodeoxycholic acid 41 using Grignard ethylation in the yield of 22% and 12% by 8 steps.In summary, anti-tubercular sterols-parguesterol A and parguesterol B and their analogues were efficiently synthesized. The method was characterized by easily available and cheap starting material, concise synthetic route, high yields, atom-economic, and laid the foundation for further development of novel antituberculous drugs.