Synthetic access to spacer-linked 3,6-diamino-2,3,6-trideoxy-alpha-D-glucopyranosides--potential aminoglycoside mimics for the inhibition of the HIV-1 TAR-RNA/Tat-peptide complex.
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.
Jöge
Thomas
T
Institut für Organische Chemie Leibniz, Universität Hannover and Zentrum für Biomolekulare Wirkstoffe (BMWZ), Schneiderberg 1B, D-30167 Hannover, Germany.
Jesberger
Martin
M
Bröker
Patrick
P
Kirschning
Andreas
A
D000617:Aminoglycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003959:Diamines; D015696:Gene Products, tat / Q000737:chemistry / Q000187:drug effects*; D005960:Glucosides / Q000138:chemical synthesis / Q000494:pharmacology*; D006027:Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006678:HIV / Q000235:genetics; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D012367:RNA, Viral / Q000737:chemistry / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
D000617:Aminoglycosides; D019380:Anti-HIV Agents; D003959:Diamines; D015696:Gene Products, tat; D005960:Glucosides; D006027:Glycosides; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus