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
Wkc. Park et al., 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, Journal of the American Chemical Society, 118(42), 1996, pp. 10150-10155
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.