Novel 5-(N-Alkylaminouracil) Acyclic Nucleosides

Abstract

Protocols for the two-step syntheses of new 5-(N-hydroxyalkyl-and 5-N-benzylamino)uracil acyclic nucleosides bearing various functional groups (alkoxy/hydroxy and cyano/ester) are presented. Two groups of the title compounds were synthesised via aminolysis of 5-bromouracil and, subsequently, either coupling with an alkylating agent (2-chloromethoxyethyl acetate), or Michael-type addition to acrylonitrile/methyl acrylate. The reverse sequences for both syntheses were also studied. The target molecules were designed as non-nucleoside reverse transcriptase inhibitors (NNRTI) and are analogues of 1-(hydroxyethoxymethyl)-6-thiophenylthymine (HEPT) and 3-benzyl-1-cyanomethyluracils. The obtained compounds will be used in screening tests for anti-HIV-1 activity.

Nucleoside Derivatives of 2,6‐Diaminopurine Antivirals: Base‐Modified Nucleosides with Broad‐Spectrum Antimicrobial Properties

“…Next, we decided to synthesize an acyclic nucleoside analog (17) of the most potent antiviral nucleobase 1 a (MR333) by functionalizing N9 with the same acyclic chain of acyclovir. Following a reported protocol, [27] we attempted to prepare (2-acetoxyethoxy)methyl acetate 15, however, compound 16 was obtained instead (Scheme 4). Nonetheless, intrigued by the possible reactivity of 16 in the coupling reaction, we decided to proceed with the synthesis by reacting compound 16 with commercial 2,6-dichloropurine 18.…”