Aldol reactions of chiral aminoaldehydes and methylacrylate in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) produces β-hydroxy methylbutenoates which can be utilized as psuedodipeptides. However, reaction of aminoaldehydes with acrylamide in the presence of DABCO afforded the adducts derived from the addition of the acrylamide nitrogen to the aldehyde to generate N-acylhemiaminals. These reactions were found to proceed at a faster rate than the typical Baylis-Hillman reaction and also require the presence of DABCO.
The chemical synthesis of certain N4-substituted imidazo[4,5-d]pyridazine and v-triazolo[4,5-d]-pyridazine nucleosides is described. In both series, the 4-chloro analogues, i.e., 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazo[4,5-d]pyr idazine (5a) and 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-v-triazolo[4,5- d]pyridazine (5b), were used as synthons to the target nucleosides. Nucleoside 5b was far more reactive toward nucleophilic displacements than 5a. Attempted deprotection of 5b was always accompanied with displacement of the 4-chloro substituent, whereas 5a was conveniently deacetylated without loss of the chloro group. Biological evaluation of the title nucleosides included antitumor studies and substrate/inhibition studies with certain purine-metabolizing enzymes. The corresponding adenosine analogues, i.e., 2-aza-3-deazaadenosine (6a) and 2,8-diaza-3-deazaadenosine (6b), were very slowly reacting substrates and weak inhibitors of bovine adenosine deaminase, whereas the inosine analogues were highly resistant to human purine nucleoside phosphorylase. The 4-benzylamino derivatives were weak inhibitors of adenosine transport into human erythrocytes. The inosine, adenosine, and selected N4-substituted analogues exhibited no in vitro toxicity toward murine L1210 leukemia and B16 melanoma cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.