ABSTRACT
The synthesis of spacer-linked neoaminoglycoside 5 is described. Key steps of the synthesis are the introduction of nitrogen functionalities at C-3 and C-6 and the olefin cross metathesis of allyl glycoside 16. Although it is known that Grubbs catalysts tolerate nitrogen functionalities, difficulties were encountered in the cross metathesis reaction. Factors that govern this dimerization are the steric and electronic demands of the catalyst and the substrate. Preliminary biological evaluation of homodimer 5, by studying the inhibition of HIV-1 TAR-RNA/Tat-peptide complex using a method based on fluorescence titration, revealed an inhibitory effect of 5.
Subject(s)
Aminoglycosides/chemistry , Aminoglycosides/pharmacology , Anti-HIV Agents/chemical synthesis , Gene Products, tat/drug effects , Glucosides/pharmacology , Glycosides/chemical synthesis , HIV Long Terminal Repeat/drug effects , Aminoglycosides/chemical synthesis , Anti-HIV Agents/pharmacology , Diamines , Gene Products, tat/chemistry , Glucosides/chemical synthesis , Glycosides/pharmacology , HIV/genetics , RNA, Viral/chemistry , RNA, Viral/drug effects , tat Gene Products, Human Immunodeficiency VirusABSTRACT
The trans reduction of all types of alkynes to give (E)-olefins is achieved through a two-stage trans hydrosilylation and protodesilylation. Reaction of an alkyne and a silane with the ruthenium catalyst [Cp*Ru(MeCN)3]PF6 results in clean hydrosilylation to give only the (Z)-trans addition product at ambient temperature with catalyst loadings of 1-5 mol %. The crude vinylsilane products are then protodesilylated by the action of cuprous iodide and TBAF at rt-35 degrees C. The reaction is compatible with many sensitive functional groups and provides a general trans-alkyne reduction not possible by other means.