合成路线:In a related procedure,aminoethylguanidine (IV) was treated with 1-methyl-4-nitropyrrole-2-carbonyl chloride (XII) producing amide (XIII).Catalytic hydrogenation of the nitro group of (XIII) gave amine (XIV),which was again coupled with acid chloride (XII).The resulting adduct (XV) was then subjected to a new hydrogenation-coupling cycle providing the tripyrrole derivative (X).
参考文献标题:Cytotoxic alpha-bromoacrylic derivatives of distamycin analogues modified at the amidino moiety
文献作者:Cozzi,P.; Beria,I.; Caldarelli,M.; Geroni,C.; Mongelli,N.; Pennella,G.
参考来源:Bioorg Med Chem Lett 2000,10(11),1273
合成路线:The reaction of Distamycin A (I) with succinic anhydride and Na2CO3 in hot DMF gives the nitrile (II),which is treated with Boc2O and DMAP in dichloromethane to yield the monocarbamate (III).The reaction of (III) with Boc2O and DMAP in DMF affords the bis carbamate (IV),which is hydrolyzed with LiOH in THF/water to provide the carboxylic acid (V).The condensation of (V) with N-(2-aminoethyl)guanidine (VI) by means of by means of TBTU in DMF gives the guanidinoethyl amide (VII),which is deprotected by means of TFA in dichloromethane to yield the aminopyrrole derivative (VIII).Finally,this compound is condensed with the acid chloride (IX) by means of NaHCO3 in dioxane/water to provide the target brostallicin.
合成路线:The hydrolysis of Distamycin A (I) with NaOH in refluxing methanol gives the aminoacid (II),which is treated with Boc2O and TEA in DMF to yield the carbamate (III).The Curtius rearrangement of (III) by means of DPPA and TEA in hot DMF affords the imidazolidinone (IV),which is hydrolyzed with NaOH in DMF to provide the 2-aminoethyl amide (V).The reaction of (V) with the protected guanidine (VI) by means of TEA in hot DMF gives the protected 2-guanidinoethyl amide (VII),which is treated with 6N HCl in methanol to eliminate the carbamoyl and trityl protecting group and yield the precursor (VIII).Finally,this compound is condensed with the acyl chloride (IX) by means of NaHCO3 in dioxane/water to afford the target brostallicin.
参考文献标题:Syntheses of brostallicin starting from distamycin A
文献作者:Nesi,M.; Beria,I.
参考来源:Tetrahedron Lett 2002,43(41),7323
合成路线:The reaction of ethylenediamine (I) with Boc2O in dioxane gives the monocarbamate (II),which is condensed with O-methylisourea (III) to yield the aminoguanidine carbamate (IV).The cleavage of the carbamate group of (IV) by means of HCl in methanol affords the aminoguanidine (V),which is condensed with 1-methyl-4-nitropyrrole-2-carbonyl chloride (VI) by means of NaHCO3 in dioxane/water to provide the amide (VII).The reduction of the nitro group of (VII) by means of H2 over Pd/C in 1N HCl affords the 4-aminopyrrole-2-carboxamide (VIII),which is condensed with the acid chloride (VI) as before to give the diamide (IX).Reduction of the nitro group of (IX) under the same conditions described above yields the amino diamide (X),which is condensed with the 14-labeled acid chloride (XI) as described above to afford the triamide (XII).Further reduction of the nitro group of (XII) gives the amino triamide (XIII),which is finally condensed with 4-(2-bromopropenamido)-1-methylpyrrole-2-carbonyl chloride (XIV) by means of NaHCO3 in dioxane/water to yield the target 14C labeled pentaamide compound.
合成路线:The reaction of deuterium labeled ethylenediamine (I) with Boc2O in dioxane gives the monocarbamate (II),which is condensed with O-methylisourea (III) to yield the labeled aminoguanidine carbamate (IV).The cleavage of the carbamate group of (IV) by means of HCl in methanol affords the aminoguanidine (V),which is condensed with 1-methyl-4-nitropyrrole-2-carbonyl chloride (VI) by means of NaHCO3 in dioxane/water to provide the amide (VII).The reduction of the nitro group of (VII) by means of H2 over Pd/C in 1N HCl affords the 4-aminopyrrole-2-carboxamide (VIII),which is condensed with the acid chloride (VI) as before to give the diamide (IX).Reduction of the nitro group of (IX) under the same conditions described above yields the amino diamide (X),which is condensed with acid chloride (VI) as described above to afford the triamide (XI).Further reduction of the nitro group of (XI) gives the amino triamide (XII),which is finally condensed with 4-(2-bromopropenamido)-1-methylpyrrole-2-carbonyl chloride (XIII) by means of NaHCO3 in dioxane/water to yield the target deuterium labeled pentaamide compound.
参考文献标题:Synthesis of brostallicin (PNU-166196A) labelled with 2H and 14C
文献作者:Fontana,E.; Pignatti,A.
参考来源:Label.Cop.& Radiopharm.2002,45(11),899
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