Solid-phase synthesis of new saphenamycin analogues with antimicrobial activity.

Abstract 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 μg/mL, comparable to the activities of previously reported saphenamycin analogues.