Solid-phase synthesis of new saphenamycin analogues with antimicrobial activity.
An array of 12 new saphenamycin analogues modified at the benzoate moiety was synthesized on solid support. Synthesis commenced with a chemoselective anchoring of saphenic acid through the carboxyl group to a 2-chlorotrityl functionalized polystyrene resin. The secondary alcohol was acylated in parallel with a series of differently substituted benzoic acid derivatives. Treatment with TFA-CH(2)Cl(2) (5:995) released the expected saphenamycin analogues into solution. These new analogues were purified, characterized and screened for antimicrobial activity against Bacillus subtilis and Proteus mirabilis. Eight analogues exhibited MIC values against B. subtilis ranging from 0.07 to 3.93 microg/mL, comparable to the activities of previously reported saphenamycin analogues.
Laursen
Jane B
JB
Department of Chemistry, Kemitorvet, Building 207, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
de Visser
Peter C
PC
Nielsen
Henrik K
HK
Jensen
Knud J
KJ
Nielsen
John
J
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010619:Phenazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011513:Proteus mirabilis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D010619:Phenazines; C036716:saphenamycin