合成路线:The cyclization of tripeptide derivative (XII) (assembled n three steps from the corresponding amino acids) by means of K2CO3/CaCO3 gives the macrocyclic peptide (XIII),which was reduced at its NO2 group with H2 over Pd/C and treated with tert-butyl nitrite,HBF4 and CuCl2 to obtain the corresponding chloro derivative (XIV).The condensation of (XIV) with the boronic acid derivative (XV) by means of a Pd catalyst affords the biphenyl derivative (XVI),which is desilylated with Bu4NF giving the secondary alcohol (XVII).The hydrolysis of the methyl ester of (XVII) with LiOH yields the corresponding carboxylic acid (XVIII).
合成路线:Selective deprotection of the benzyloxycarbonylamino group of (XVIII) with H2 over Pd/C gives the corresponding amino derivative (XIX),which is cyclized by means of EDC and HOBT yielding the bicyclic peptide (XX).Elimination of the Boc protecting group of (XX) with formic acid affords the primary amine (XXI),which is acylated with the previously obtained dipeptide intermediate (XI) by means of DEPBT providing the adduct (XXII).
合成路线:The cyclization of tripeptide derivative (I) (assembled in three steps from the corresponding amino acids) by means of K2CO3/CaCO3 gives the macrocyclic peptide (II),which was reduced at its NO2 group with H2 over Pd/C and treated with tert-butyl nitrite,HBF4 and CuCl2 to obtain the corresponding chloro derivative (III).The condensation of (III) with the boronic acid derivative (IV) by means of a Pd catalyst affords the biphenyl derivative (V),which is desilylated with Bu4NF,giving the secondary alcohol (VI).The hydrolysis of the methyl ester of (VI) with LiOH yields the corresponding carboxylic acid (VII).
合成路线:Selective deprotection of the benzyloxycarbonylamino group of (VII) with H2 over Pd/C gives the corresponding amino derivative (VIII),which is cyclized by means of EDC and HOBT,yielding the bicyclic peptide (IX).Elimination of the Boc protecting group of (IX) with formic acid affords the primary amine (X) ,which is acylated with the tripeptide intermediate (XI) by means of EDC and HOAt,providing the adduct (XII).
合成路线:The cyclization of (XII) by means of CsF in DMSO gives the tris macrocyclic compound (XIII),which is reduced at the NO2 group with H2 over Pd/C,yielding the amino derivative (XIV).The diazotation of (XIV) with t-Bu-ONO and HBF4,followed by reaction with CuCl2/CuCl,affords the corresponding chloro derivative (XV),which is silylated with Tbdms-N(Me)-COCF3 to provide the bis silyl ether (XVI).
合成路线:Elimination of the Mem protecting group of (XVI) by treatment with borane (XVII) gives the primary alcohol (XVIII),which is oxidated to the corresponding acid with DMP and NaClO2 and simultaneously methylated with Tms-CHN2 to yield the methyl ester (XIX).The controlled hydrolysis of the cyano group of (XIX) with H2O2 and K2CO3 affords the corresponding amide (XX),which is finally desilylated with TBAF and demethylated with AlBr3 to furnish the target aglycon.
参考文献标题:Total synthesis of the vancomycin aglycon
文献作者:Boger,D.L.; et al.
参考来源:J Am Chem Soc 1999,121(43),10004
合成路线:Assembly of the target compound: The condensation of the carboxylic acid intermediate (XXI) with the free amino group of the intermediate cyclopeptide (XXII) by means of DEPBT gives the corresponding amide (XXIII),which is cyclized by means of CsF in DMSO yielding the macrocyclic ether (XXIV).The reduction of the nitro group of (XXIV) with H2 over Pd/C affords the corresponding amino derivative (XXV).
合成路线:The cyclization of tripeptide derivative (I) (assembled in three steps from the corresponding amino acids) by means of K2CO3/CaCO3 gives the macrocyclic peptide (II),which was reduced at its NO2 group with H2 over Pd/C and treated with tert-butyl nitrite,HBF4 and CuCl2 to obtain the corresponding chloro derivative (III).The condensation of (III) with the boronic acid derivative (IV) by means of a Pd catalyst affords the biphenyl derivative (V),which is desilylated with Bu4NF,giving the secondary alcohol (VI).The hydrolysis of the methyl ester of (VI) with LiOH yields the corresponding carboxylic acid (VII).
合成路线:Selective deprotection of the benzyloxycarbonylamino group of (VII) with H2 over Pd/C gives the corresponding amino derivative (VIII),which is cyclized by means of EDC and HOBT,yielding the bicyclic peptide (IX).Elimination of the Boc protecting group of (IX) with formic acid affords the primary amine (X) ,which is acylated with the tripeptide intermediate (XI) by means of EDC and HOAt,providing the adduct (XII).
合成路线:The cyclization of (XII) by means of CsF in DMSO gives the tris macrocyclic compound (XIII),which is reduced at the NO2 group with H2 over Pd/C,yielding the amino derivative (XIV).The diazotation of (XIV) with t-Bu-ONO and HBF4,followed by reaction with CuCl2/CuCl,affords the corresponding chloro derivative (XV),which is silylated with Tbdms-N(Me)-COCF3 to provide the bis silyl ether (XVI).
合成路线:Elimination of the Mem protecting group of (XVI) by treatment with borane (XVII) gives the primary alcohol (XVIII),which is oxidated to the corresponding acid with DMP and NaClO2 and simultaneously methylated with Tms-CHN2 to yield the methyl ester (XIX).The controlled hydrolysis of the cyano group of (XIX) with H2O2 and K2CO3 affords the corresponding amide (XX),which is finally desilylated with TBAF and demethylated with AlBr3 to furnish the target aglycon.
参考文献标题:Diasteroselective total synthesis of the vancomycin aglycon with ordered atropisomer equilibrations
文献作者:Boger,D.L.; et al.
参考来源:J Am Chem Soc 1999,121(13),3226
产品链接: CAS No. 1404-93-9›› 产品链接: CAS No.1404-90-6››