合成路线:The ozonolysis of cylcoheptene (I) with O3 in dichloromethane,followed by a treatment with methanol and p-toluenesulfonic acid gives 7,7-dimethoxyheptanal (II),which is condensed with methoxycarbonyl-methylenetriphenylphosphorane (III) in methanol yielding methyl 9,9-dimethoxy-2-nonenoate (IV).The condensation of (IV) with 2(S)-(tetrahydropyranyloxy)propanal (V) by means of LDA in THF/HMPA affords the beta-hydroxyester (VI),which is cyclized by means of p-toluenesulfonic acid and mesyl chloride affording the furanone (VII).The hydrolysis of the acetal group of (VII) with Amberlyst 15 gives the aldehyde (VIII),which is condensed with the phosphorane (IX) yielding the unsaturated thioester (X).The cyclization of (XV) by means of Et2AlCl in toluene affords the tricyclic thioester (XI),which is reduced with RaNi in ethanol/ethyl ether affording the carbinol (XII).The reaction of (XII) with tosyl chloride and thiophenol provides the pheylsulfanyl derivative (XIII),which is reduced at the lactone group with iBu2AlH in ethyl ether giving the lactol (XIV).The methylation of the lactol (XIV) with BF3/Et2O and methanol yields the cyclic ketal (XV),which is finally oxidized with meta-chloroperbenzoic acid (MCPBA) in dichloromethane to afford the desired tricyclic sulfone intermediate (XVI).
合成路线:The reduction of piperidine-2(R)-carboxylic acid (XVII) with BH3/Me2S and BF3/Et2O in THF gives the carbinol (XVIII),which is treated with Boc2O and NaOH in THF yielding the carbamate (XIX).The silylation of the carbinol group of (XIX) with TBDMS-Cl and imidazole in DMF affords the silyl ether (XX),which is methylated with BuLi and methyl iodide providing the 2-methyl derivative (XXI).The desilylation of (XXI) with TBAF in THF affords the free carbinol (XXII),which is oxidized to the corresponding aldehyde (XXIII) with RuO4NPr4.The condensation of aldehyde (XXII) with the tricyclic sulfone intermediate (XVI) by means of BuLi in DME and sodium amalgam in methanol yields the vinylpiperidine intermediate (XVII),which is oxidized at the lactol group with Jones reagent (CrO3,H2SO4) giving the tricyclic lactone (XVIII).The deprotection of the piperidine ring of (XVIII) with TFA in dichloromethane yields the intermediate (XIX),which is finally methylated with formaldehyde and sodium cyanoborohydride in acetonitrile/water.
参考文献标题:Total syntheses of (+)-Himbacine and (-)-Himbeline
文献作者:Hart,D.J.and Wu,W.-L.
参考来源:J Am Chem Soc 1995,1179369
合成路线:The ozonolysis of cylcoheptene (I) with O3 in dichloromethane,followed by a treatment with methanol and p-toluenesulfonic acid gives 7,7-dimethoxyheptanal (II),which is condensed with methoxycarbonyl-methylenetriphenylphosphorane (III) in methanol yielding methyl 9,9-dimethoxy-2-nonenoate (IV).The condensation of (IV) with 2(S)-(tetrahydropyranyloxy)propanal (V) by means of LDA in THF/HMPA affords the beta-hydroxyester (VI),which is cyclized by means of p-toluenesulfonic acid and mesyl chloride affording the furanone (VII).The hydrolysis of the acetal group of (VII) with Amberlyst 15 gives the aldehyde (VIII),which is condensed with the phosphorane (IX) yielding the unsaturated thioester (X).The cyclization of (XV) by means of Et2AlCl in toluene affords the tricyclic thioester (XI),which is reduced with RaNi in ethanol/ethyl ether affording the carbinol (XII).The reaction of (XII) with tosyl chloride and thiophenol provides the pheylsulfanyl derivative (XIII),which is reduced at the lactone group with iBu2AlH in ethyl ether giving the lactol (XIV).The methylation of the lactol (XIV) with BF3/Et2O and methanol yields the cyclic ketal (XV),which is finally oxidized with meta-chloroperbenzoic acid (MCPBA) in dichloromethane to afford the desired tricyclic sulfone intermediate (XVI).
合成路线:The reduction of piperidine-2(R)-carboxylic acid (XVII) with BH3/Me2S and BF3/Et2O in THF gives the carbinol (XVIII),which is treated with Boc2O and NaOH in THF yielding the carbamate (XIX).The silylation of the carbinol group of (XIX) with TBDMS-Cl and imidazole in DMF affords the silyl ether (XX),which is methylated with BuLi and methyl iodide providing the 2-methyl derivative (XXI).The desilylation of (XXI) with TBAF in THF affords the free carbinol (XXII),which is oxidized to the corresponding aldehyde (XXIII) with RuO4NPr4.The condensation of aldehyde (XXII) with the tricyclic sulfone intermediate (XVI) by means of BuLi in DME and sodium amalgam in methanol yields the vinylpiperidine intermediate (XVII),which is oxidized at the lactol group with Jones reagent (CrO3,H2SO4) giving the tricyclic lactone (XVIII).The deprotection of the piperidine ring of (XVIII) with TFA in dichloromethane yields the intermediate (XIX),which is finally methylated with formaldehyde and sodium cyanoborohydride in acetonitrile/water.
参考文献标题:Applications of Organosulfur Chemistry to Organic Synthesis: Total Synthesis of (+)-Himbeline and (-)-Himbacine
文献作者:Wu,W.-L.; Hart,D.J.; Li,J.
参考来源:J Org Chem 1997,625023
产品链接: CAS No. 6879-74-9››