NONIONIC TRIMODULAR BIOACTIVE SURFACTANTS CONTAINING A BETA-LACTAME RING AND A SUGAR

A synthetic methodology for surfactant molecules containing a beta-lac tame ring and a glycosamine has been developed. From 3-hydroxy-2-hydro xymethyl-2-methyl-propionic acid we prepared a hydrophobic 1,3-diol mo dule A by selective amidation using a fatty amine. One of the primary alcohol functions of this product A is selectively activated in the fo rm of the ATDP sit B. The cyclization of B into the beta-lactame C is then effected by reaction in a basic medium (K2CO3). These derivatives C: constitute an interesting bimodular surfactant. By esterification of C with succinic anhydride we obtained products D. The carboxy[ic fu nction introduced by the succinyl group was activated by BOP and coupl ed to the glucosamine giving the trimodular biotensides E. These deriv atives display air-water interface activity as shown by the surface te nsion; the values of which have been lowered to 32 mN/m. The Critical Micellar Concentration (CMC) is of the order of 10(-4) mol dm(-3), com parable in magnitude to what has been observed for surfactants with su gar-type polar heads. Binary phase diagrams with water for these produ cts C, as a function of temperature and concentration, show the behavi or of hydrophilic surfactants with a large direct micellar phase L-1. Products E show little toxicity in cell culture, however they induce a poptosis at concentrations larger than 3x10(-4) g/L. They also show an tibiotic properties with respect to gram(+) or gram(-) bacterial strai ns with Minimal Inhibition Concentrations (MIG) on the order of 32 mu g/mL in the cases where they appear to be the most efficient. These va lues remain, however, below those of commercial monobactames.