Synthesis and Conformational Analysis of Fluorinated Uridine Analogues Provide Insight into a Neighbouring-Group Participation Mechanism

Fluorinated nucleoside analogues have attracted much attention as anticancer and antiviral agents and as probes for enzymatic function. However, the lack of direct synthetic methods, especially for 2′,3′-dideoxy-2′,3′-difluoro nucleosides, hamper their practical utility. In order to design more efficient synthetic methods, a better understanding of the conformation and mechanism of formation of these molecules is important. Herein, we report the synthesis and conformational analysis of a 2′,3′-dideoxy-2′,3′-difluoro and a 2′-deoxy-2′-fluoro uridine derivative and provide an insight into the reaction mechanism. We suggest that the transformation most likely diverges from the SN1 or SN2 pathway, but instead operates via a neighbouring-group participation mechanism.

Double neighbouring group participation for ultrafast exchange in phthalate monoester networks

We introduce here the rapid transesterification of phthalate monoester-based covalent adaptable networks thanks to a double neighbouring group participation effect.

Dehydroxylated amination accompanied by 1,2-sulfur immigration

A sulfur neighbouring-group participation N-alkylation method is presented, which enables the simultaneous C–O cleavage, C–S immigration and C–N formation performed in a metal free system.

S-O acetyl rearrangement in 6-thio-D-glucose derivatives

The solvolytic reaction of 1,2-O-isopropylidene-3,6-di-O-(p-toluenesulphonyl)- ?-D-glucofuranose (2), as well as that of 6-chloro-6-deoxy-1,2-O-isopropylidene-3-O-(p-toluenesulphonyl)-?-D-glucofuranose (3), in the presence of potassium thioacetate unexpectedly gave the 6-S-acetyl-5-O-acetyl derivative 5 as the main reaction product. A possible mechanism of these transformations was postulated whereby the main role was ascribed to a neighbouring group participation process, involving hydrogen thio-orthoester formation as an intermediate. The regiospecific monosubstitution of the 6-tosyloxy group in compound 2 was successfully achieved with potassium thioacetate, in presence of 2,3-benzo-15-crown-5 as a catalyst. The corresponding 6-S-acetyl derivative 7 was obtained representing a possible intermediate in the mentioned solvolytic reactions. Compound 7 was shown to be very reactive, since it fully transformed into the corresponding mercaptan 8 in the presence of silica gel. This transformation occurred via the same thio-orthoester 7a as in the mentioned solvolytic reactions of furanoses 2 and 3. The synthesized compounds are key intermediates in the planned synthesis of selected natural products and their analogues.