Impact of the central hydroxyl groups on the activity of symmetrical HIV-1 protease inhibitors derived from L-mannaric acid
2000 (English)In: Tetrahedron, ISSN 0040-4020, Vol. 56, no 20, 3219-3225 p.Article in journal (Refereed) Published
The influence of the central hydroxyl groups on the anti-viral activity of symmetrical HIV-1 protease inhibitors derived from L-mannaric acid has been examined. L-Iditol was synthesized and used as a chiral precursor for the synthesis of the corresponding inhibitor with inverted configuration at C-3 and C-4. Key intermediates were 3,4-O-isopropylidene-L-iditol and the activated L-idaric acid succinimidyI ester. The configurations of the central hydroxyl groups required for optimal inhibition of the HIV-1 protease were determined to be the C-3R and C-4R, i.e. the L-manno-configuration. Three C2-symmetric inhibitors were converted to their thiocarbonates and reduced to provide the corresponding hydroxyethyl transition-state mimics. Deletion of the C-4 hydroxyl group in these inhibitors gave no further improvement in the anti-viral activity. (C) 2000 Published by Elsevier Science Ltd.
Place, publisher, year, edition, pages
2000. Vol. 56, no 20, 3219-3225 p.
Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-47651DOI: 10.1016/S0040-4020(00)00220-9OAI: oai:DiVA.org:liu-47651DiVA: diva2:268547