- Efficient Total Syntheses of the Oligopeptide Antibiotics Netropsin and Distamycin
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New and efficient total syntheses of the natural oligopeptide antiviral antibiotics netropsin and distamycin are described.These procedures feature a different strategy of introduction of the terminal groups from that used hitherto, high yield coupling steps, improvements in the Pinner reaction for introducing the amidine moiety, and the novel use of N-formylimidazole for introduction of the formyl moiety in distamycin.The methods also avoid column chromatography with the attendant contamination of the oligopeptide hydrochlorides with inorganic salts eluted from adsorbents.The synthetic procedures are general and may be adapted to the synthesis of related oligopeptide structures.
- Lown, J. William,Krowicki, Krzysztof
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p. 3774 - 3779
(2007/10/02)
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- Novel Efficient Total Synthesis of Antiviral Antibiotic Distamycin A
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In connection with an attempt to design a flexible synthesis of analogues of distamycin A (14) for a structure-activity study, by starting from 4-amino>-1-methylpyrrole-2-carboxylic acid (3) and the corresponding formyl derivative (9), the distamycin A precursor 12 was prepared.The versatility of 12 is demonstrated by direct attachment, after activation, of preformed β-aminopropionamidine dihydrobromide to give 14 in fair yield.We conclude that N- and/or ring-substituted derivatives of 3 and 9 may lead to the corresponding analogues of 12 and thus serve as useful precursors, to which the amino amidine or derivatives thereof can be attached.After hydrogenation of the corresponding nitro compound, 3 and 9 were prepared with (tert-butyloxy)carbonyl fluoride and formic anhydride, respectively.Amide bond formations were accomplished with carbodiimides, occasionally via intermediary active esters (8,13).
- Grehn, Leif,Ragnarsson, Ulf
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p. 3492 - 3497
(2007/10/02)
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