1924-30-7Relevant articles and documents
Synthesis of annelated analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442) using 1,3-oxazine-2,4(3H)-diones as key intermediates
Larsen, Janus S.,Christensen, Lene,Ludvig, Gitte,Jorgensen, Per T.,Pedersen, Erik B.,Nielsen, Claus
, p. 3035 - 3038 (2000)
Condensation of ethyl 3-phenyl-2-oxocyclopentanecarboxylate 5 with 2-(S-methylthio)isourea followed by hydrolysis with HC1 gave 6,7-dihydro-7-phenylcyclopenta[e][1,3]oxazine-2,4(3H,5H)-dione (10a). 7,8-Dihydro-8-phenyl-6H-cyclohexa[e][1,3]oxazine-2,4(3H,5H)-dione (10b) was synthesised by reacting 2-phenylcyclohexanone (9b) with N-(chlorocarbonyl) isocyanate. The oxazines 10a,b were reacted with ammonia to obtain the corresponding uracil derivatives 12a,b which after silylation were alkylated with diethoxymethane using trimethylsilyl triflate (TMS-triflate) as the catalyst or alkylated with chloromethyl ethyl ether to give annelated MKC-442 analogues 2,3 which are locked in a conformation close to the one of MKC-442. In spite of this, only moderate activities were found against HIV-1 for the annelated analogues of MKC-442. The Royal Society of Chemistry 2000.