- A convenient synthesis of racemic and optically active 1-aza-1,3-dienes derived from γ-amino esters: Reduction to α,β-unsaturated and saturated γ-amino acid derivatives
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A simple synthesis of racemic and optically active 1-azadienes derived from γ-amino esters by olefination reaction of alkyl glyoxylates and functionalized phosphonium salts or phosphine oxides is reported. Selective reduction of these 1-azadienes with hydrides yields (E)-γ-amino-α,β-unsaturated esters. A simple procedure for the preparation of saturated γ-amino acids and γ-amino esters from the previously synthesized vinylogous amino esters is also described.
- Palacios, Francisco,Aparicio, Domitila,García, Jesús,Rodríguez, Encina,Fernández-Acebes, Alvaro
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p. 3131 - 3141
(2007/10/03)
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- Man-designed bleomycin with altered sequence specificity in DNA cleavage
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The synthetic approach to the concerted antitumor mechanism of bleomycin is studied by introducing a dynamic change into the O2-activation moiety and DNA-binding site. A model PYML(6)-bleomycin previously reported, possessing an oxygen-activating methoxypyridine moiety and a DNA-binding bithiazole moiety, exhibits a nucleotide cleavage mode virtually identical with that of bleomycin. Herein reported is a newly designed bleomycin analogue, PYML(6)-(4R-APA)-distamycin, wherein the 4-methoxypyridine moiety and a DNA-binding distamycin component are connected through an (R)-4-aminopentanoic acid linker moiety. Synthesis of PYML(6)-(4R-APA)-distamycin is carried out by condensation of the hydroxyhistidine-pentatoic acid fragment with the methoxypyridien moiety, followed by introducing of the distamycin moiety. PYML(6)-(4R-APA)-distamycin cleaves a G4 phage DNA fragment (100 base pairs) at 1 μM concentration in the presence of Fe(II), oxygen, and dithiothreitol and induces dramatically altered adenine/thymine specificity. It is indicated that the specific recognition of base sequences for the cleavage is mainly controlled by the DNA affinity site and that the (R)-4-aminopentanoic acid linker seems to determine the proper arrangement of the iron-oxygen site and the distamycin moiety on DNA.
- Otsuka,Masuda,Haupt,Ohno,Shiraki,Sugiura,Maeda
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p. 838 - 845
(2007/10/02)
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