合成路线:1) The cyclization of meso-2,6-bis(benzyloxycarbonylamino)heptanedioic acid (I) with PCl5 gives the corresponding bis oxazolidinedione (II),which is treated with tert-butyl carbazate (III) yielding the bis hydrazide (IV).Enzymatic hydrolysis of (IV) with Streptomyces sapporonensis affords the (S)-monoacid (V),which is selectively protected with benzyl chloroformate and copper chelate (VI).A second protection reaction of (VI) with tert-butoxycarbonyl anhydride gives the amino protected acid (VII) ,which is condensed with D-alanine benzyl ester (VIII) by means of isobutyl chloroformate to afford the acylated D-alanine (IX).Elimination of the benzyloxycarbonyl groups of (IX) by hydrogenolysis yields compound (X) with a free amino group,which is condensed with N-heptanoyl-D-glutamic acid 1-benzyl monoester (XI) to give the protected FK-565 precursor (XII).Finally,this compound is deprotected with trifluoroacetic acid and sodium periodate.
参考文献标题:Synthesis and RES-stimulating activity of bacterial cell-wall peptidoglycan peptides related to FK-156
文献作者:Kitaura,Y.; Takeno,H.; Aratani,M.; Okada,S.; Yonishi,S.; Hemmi,K.; Nakaguchi,O.; Hashimoto,M.
参考来源:Experientia 1982,381101-3
合成路线:1) The cyclization of meso-2,6-bis(benzyloxycarbonylamino)heptanedioic acid (I) with PCl5 gives the corresponding bis oxazolidinedione (II),which is treated with tert-butyl carbazate (III) yielding the bis hydrazide (IV).Enzymatic hydrolysis of (IV) with Streptomyces sapporonensis affords the (S)-monoacid (V),which is selectively protected with benzyl chloroformate and copper chelate (VI).A second protection reaction of (VI) with tert-butoxycarbonyl anhydride gives the amino protected acid (VII) ,which is condensed with D-alanine benzyl ester (VIII) by means of isobutyl chloroformate to afford the acylated D-alanine (IX).Elimination of the benzyloxycarbonyl groups of (IX) by hydrogenolysis yields compound (X) with a free amino group,which is condensed with N-heptanoyl-D-glutamic acid 1-benzyl monoester (XI) to give the protected FK-565 precursor (XII).Finally,this compound is deprotected with trifluoroacetic acid and sodium periodate.
参考文献标题:Total synthesis of FK-156 isolated from a Streptomyces as an immunostimulating peptide: Application of a novel copper chelate amino protection
文献作者:Takeno,H.; Kitaura,Y.; Hashimoto,M.; Hemmi,K.; Nakaguchi,O.; Okada,S.
参考来源:J Am Chem Soc 1981,103(23),7026-8
合成路线:2) The methylation of meso-2,6-bis(benzyloxycarbonylamino)heptanedioic acid (I) with diazomethane gives the corresponding dimethyl ester (XIII),which is submitted to a selective hydrolysis with a protease type VIII enzyme yielding the monoester (XIV).The cyclization of (XIV) with PCl5 affords the oxazolidinedione (XV),which is condensed with D-alanine 4-nitrobenzyl ester (XVI) to give compound (XVII) with a free amino group that is condensed with D-glutamic acid monoester (XI) affording the fully protected FK-565 derivative (XVIII),which is first debenzylated by hydrogenolysis to methyl ester (XIX),and finally hydrolyzed with NaOH.
参考文献标题:New convenient synthesis of immunostimulating peptides containing meso-diaminopimelic acid.Syntheses of FK-565 and FK-156
文献作者:Kolodziejczyk,A.M.; Stoev,S.; Kolodziejczyk,A.S.
参考来源:Int J Pept Protein Res 1992,39282-7
产品链接: CAS No. 79335-75-4››