Preparation of basic prolineamide derivatives of GE2270 and GE2270-like antibiotics

Abstract

Title compds. [I; R1 = H, alkyl, dialkylaminoalkylene; X = alkylene, alkylenecarbonyl; R2 = amino, 5-6 membered N-heterocyclyl; R1R2 = atoms to form a (substituted) 5-6 membered heterocyclic ring; W1 = Ph; W2 = OH; or W1, W2 both = Me; X1 = H, Me; X2 = H, Me, MeOCH2; when both W1, W2 = Me, then X1 = Me and X2 = H], were prepd. Thus, GE2270 factor A3 was condensed with H-Ser-Pro-NHCH2CH2NEt2 hydrochloride (prepn. given) using Et3N/DPPA in DMF and the condensation product in THF was treated with Burgess reagent in CH2Cl2 followed by Me2CHOH quench and reflux to give I; (R1 = H; XR2 = CH2CH2NEt2; W1 = Ph; W2 = OH; X1 = Me; X2 = MeOCH2). The latter showed a min. inhibitory concn. of 0.06 \u3bcg/mL against Staphylococcus aureus