ABSTRACT
Nucleophilic enamines add spontaneously on heteroarenes 3-nitroindole and benzofuran to form a new C-C bond. With nitroindole and enamine , an unprecedented dearomatizing formal ene reaction occurs in a totally regio- and diastereo-selective manner. With 3-nitrobenzofuran and enamine , the reaction course is different and leads to the generation of a dienylphenol.
ABSTRACT
Non-stabilized azomethine ylide 4a reacts smoothly at room temperature with a variety of uncomplexed aromatic heterocycles and carbocycles on the condition that the ring contains at least one or two electron-withdrawing substituents, respectively. Aromatic substrates, including pyridine and benzene derivatives, participate as 2π components in [3+2] cycloaddition reactions and interact with one, two, or three equivalent(s) of the ylide, depending on their structure and substitution pattern. Thus, this process affords highly functionalized polycyclic structures that contain between one and three pyrrolidinyl ring(s) in useful yields. These results indicate that the site selectivity of the cycloaddition reactions strongly depends on both the nature and the positions of the substituents. In most cases, the second 1,3-dipolar reaction occurs on the opposite face to the one that contains the first pyrrolidinyl ring. DFT calculations on model compounds indicate that a concerted mechanism features a low activation barrier.
ABSTRACT
The synthesis of new class of potential TPase inhibitors containing a difluoromethylphosphonate function as phosphate mimic is reported. This new series was prepared from a readily available fluorinated building block in few steps. Two series were evaluated as potential inhibitors: a linear series and a conformational constrained series. The activity of these multisubstrate inhibitors depends on the size of the spacer introduced between the pyrimidine ring and the phosphonate function. Best results were observed from triazolyl derivatives, easily obtained from propargylthymine and corresponding azides.
Subject(s)
Angiogenesis Inhibitors/chemical synthesis , Nucleosides/chemical synthesis , Organophosphonates/chemical synthesis , Thymidine Phosphorylase/antagonists & inhibitors , Angiogenesis Inhibitors/chemistry , Crystallography, X-Ray , Escherichia coli/enzymology , Models, Molecular , Molecular Conformation , Molecular Structure , Nucleosides/chemistry , Organophosphonates/chemistry , Structure-Activity Relationship , Substrate Specificity , Thymidine Phosphorylase/chemistryABSTRACT
Preparation of several acyclonucleosides containing both a difluoromethylphosphonate group and a triazole moiety is described starting from a difluorophosphonosulfide. The key step of the synthesis involves a copper(I)-catalyzed Huisgen 1-3 dipolar cycloaddition between difluorophosphonylated azides and propargylated nucleobases derived from thymine and 2-amino-6-chloropurine.
Subject(s)
Copper/chemistry , Nucleotides/chemistry , Nucleotides/chemical synthesis , Organophosphonates/chemistry , Alkynes/chemistry , CatalysisABSTRACT
Ring-opening reactions of functionalized 1,2-cyclic sulfates and oxetanes with the phosphonodifluoromethyl carbanion are reported. This approach allows an easy access to fluorinated beta-hydroxyphosphonates that are building blocks in the synthesis of acyclic nucleosides. Synthesis of precursors of nucleoside phosphorylase inhibitors from these alcohols is described.