Phosphonoxins III: Synthesis of α-Aminophosphonate Analogs of Antifungal Polyoxins with Anti-Giardia Activity

A synthesis of α-aminophosphonate analogs of polyoxins, termed phosphonoxin C1, C2, and C3, has been achieved. The key step was the addition of lithium dimethyl phosphite to the aldehyde of a protected threose derivative. α-Hydroxyphosphonate analogs C4 and C5 were also obtained by taking advantage...

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Bibliographic Details
Published in:Organic letters 2010-10, Vol.12 (20), p.4596-4599
Main Authors: Staake, Michael, Chauhan, Jay, Zhou, Ding, Shanker, Aaron, Chatterjee, Atasi De, Das, Siddhartha, Patterson, Steven E
Format: Article
Language:English
Subjects:
Antifungal Agents - chemical synthesis
Antifungal Agents - pharmacology
Giardia lamblia - drug effects
Molecular Structure
Organophosphonates
Pyrimidine Nucleosides - chemical synthesis
Pyrimidine Nucleosides - chemistry
Pyrimidine Nucleosides - pharmacology
Stereoisomerism
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Summary:A synthesis of α-aminophosphonate analogs of polyoxins, termed phosphonoxin C1, C2, and C3, has been achieved. The key step was the addition of lithium dimethyl phosphite to the aldehyde of a protected threose derivative. α-Hydroxyphosphonate analogs C4 and C5 were also obtained by taking advantage of an unprecedented conversion of an azide to hydroxyl during treatment with hydrogen on palladium on carbon. The resulting phosphonoxin C5 inhibited the growth of an intestinal protozoan, Giardia lamblia, at low micromolar concentration.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol101913t