Solid‐Phase Microwave‐Assisted Ligand‐Free Suzuki‐Miyaura Cross‐Coupling of 5‐Iodouridine

Abstract

A soild-supported 5-iodouridine derivative underwent Suzuki-Miyaura cross-coupling reactions with various aryl/heteroarylboronic acids under microwave-assisted ligand-free conditions yielding 5-aryl/heteroaryl uridine derivatives. Reactions were performed using Pd(dppf)Cl 2 · CH 2 Cl 2 as catalyst and K 3 PO 4 as base in a tert-BuOH/toluene/water solvent system. In our synthetic strategy uridine nucleosides were anchored onto 2-chlorotrityl chloride resin through an acetal linkage blocking the 2' -and 3' -OH of the ribose moiety thus allowing an enormous opportunity for modifications on the nucleobase or on the 5'-position. The described method offers an acid labile acetal linker strategy thus allowing potential application in Fmoc-Solid-Phase Peptide Synthesis or late stage modification of uridyl peptide nucleoside antibiotic analogues synthesis.

Novel Furan-2-yl-1H-pyrazoles Possess Inhibitory Activity against α-Synuclein Aggregation

“…The cross-coupling reactions of the furaldehydes forming 6a – 6e were typically high-yielding; however, the reaction with 3-chlorophenylboronic acid afforded very poor yields of the desired product ( 6b ). All attempts were made to improve the product yield by varying the reaction conditions (such as increasing the temperature or molar equivalents of reactants and/or reagents) but failed. Interestingly, ( E )-3-(5-(3-chlorophenyl)­furan-2-yl)­acrylaldehyde (Figure S1), the product of ethanol’s condensation with the 2-formyl derivatives, was isolated as the major product, and the ( E )-isomer was formed exclusively.…”

Transition Metal‐Catalyzed Reactions and Solid‐Phase Synthesis: A Convenient Blend

“…Finally, another interesting work published within the analyzed period, describes the construction of a library of 5aryl/heteroaryl uridine analogues. [59] For that, a 5-iodouridine derivative was linked to the 2-chlorotrityl chloride resin through an acetal functional group, rendering 116 (Scheme 24), which underwent Suzuki-Miyaura cross-coupling reaction under MW heating, to give 117 in 63-90 % yield. The acetal linker remained inert throughout the reaction, being separated from the desired uridine with TFA.…”

Simplified Novel Muraymycin Analogues; using a Serine Template Strategy for Linking Key Pharmacophores

“…Synthetic access to this 5-glycyluridine (GlyU) core unit is not trivial and involves multi-step challenging synthetic routes. 25 Henceforth, to achieve the prime objective of chemically simplified muraymycins analogues, we have selected a serine template as a linker to which the desired key pharmacophores can be linked via conventional amide-coupling methodologies (5, Figure 4). Additionally, we also aimed to vary the lipophilic side chain by investigating the linear carbon chain length to achieve optimised antibacterial activity.…”

“…Therefore development of antibacterial agents targeting enzymes involved in these initial stages could provide an exciting opportunity to meet the current need for novel targets. 6 The transmembrane enzyme MraY (phospho-N-acetylmuramoylpentapeptide-transferase; translocase I) is one such enzyme with its active site located on the cytosolic side of the membrane, which fulfils the requirement of a novel target. 7 MraY catalyses the first membrane-associated step of peptidoglycan formation which involves transfer of an UDP-N-acetylmuramoyl (UDP-MurNAc)pentapeptide (-L-Ala--D-Glu-diaminopimelic acid/L-Lys-D-Ala-D-Ala) (Park's nucleotide) to the lipid carrier [C55 isoprenoid phosphate (C55-P)/C50 decaprenyl phosphate (C50-P)], resulting in the formation of lipid I (undecaprenyl-pyrophosphoryl-MurNAcpentapeptide) (Figure 1).…”