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 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.
Staake
Michael
M
Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Chauhan
Jay
J
Zhou
Ding
D
Shanker
Aaron
A
De Chatterjee
Atasi
A
Das
Siddhartha
S
Patterson
Steven E
SE
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016829:Giardia lamblia / Q000187:drug effects*; D015394:Molecular Structure; D063065:Organophosphonates; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D000935:Antifungal Agents; D063065:Organophosphonates; D011741:Pyrimidine Nucleosides; C002457:polyoxin