RAPID COMBINATORIAL SYNTHESIS OF AMINOGLYCOSIDE ANTIBIOTIC MIMETICS -USE OF A POLYETHYLENE GLYCOL-LINKED AMINE AND A NEAMINE-DERIVED ALDEHYDE IN MULTIPLE COMPONENT CONDENSATION AS A STRATEGY FOR THE DISCOVERYOF NEW INHIBITORS OF THE HIV RNA REV RESPONSIVE ELEMENT

A library of neomycin B mimetics has been prepared rapidly without chr omatography using a neamine-derived aldehyde, tert-butyl isocyanide or isocyanoacetic acid methyl ester, a glycine-conjugated polyethylene g lycol (PEG) methyl ether, and various Cbz-N-protected amino acids as s ubstrates in a Ugi-type one-pot reaction. The product linked to PEG wa s isolated by precipitation in ether. A simultaneous base-catalyzed hy drolysis and de-O-acetylation followed by hydrogenation provided an ea sy access to a library of neomycin B mimetics, which were screened for binding to the Rev responsive element of HIV mRNA (RRE). Several prod ucts were found to be more active than neamine with the IC50 values in the micromolar range.