1. Nucleic Acid Center, Department of Chemistry and Physics, University of Southern Denmark, Campusvej 55, DK‐5230 Odense M, Denmark;2. On leave from chemistry department, faculty of education Kafr El‐Sheikh branch, Tanta University, Kafr El‐Sheikh Egypt.;3. Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Microbiologia e Virologia Generale e Biotecnologie Microbiche, Universita di Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy
Abstract:
Reaction of 1,3‐phenylenediacetonitrile with the zinc organometallic reagent of ethyl 2‐bromobutyrate afforded the 1,3‐phenylene‐bis(acetoacetate) 2 which was used as the starting material for the synthesis of 1,3‐phenylene‐bis6‐(2‐thiouracil)] 4 . Desulphurization of 4 gave the corresponding bis‐uracil 6 , which after silylation was N‐1 alkylated with bis(allyoxy)methane using TMS‐triflate as the catalyst or with chloromethyl ethyl ether to give the MKC‐442 analogues 7 and 9 . The amino‐DABO and S‐DABO derivatives 11, 12a,b and 14 were also synthesized. The anti‐HIV‐1 activity test showed that when MKC‐442 analogues were constructed with 1,3‐phenylene in all cases they were detrimental to have activity against HIV‐1.
