A tandem catalysis protocol based on decarboxylative coupling of alkynoic acids and 1,3-dipolar cycloaddition of azides enables a highly efficient synthesis of a variety of functionalized 1,2,3-triazoles. The three-step, one-pot method avoids usage of gaseous or highly volatile terminal alkynes, reduces handling of potentially unstable and explosive azides to a minimum, and furnishes target structures in excellent yields and a very good purity without the need for additional purification.

DNA and RNA oligonucleotides having formacetal internucleoside linkages between uridine and adenosine nucleosides have been prepared and studied using UV thermal melting, osmotic stress and X-ray crystallography. Formacetal modifications have remarkably different effect on double helical RNA and DNA -the formacetal stabilizes RNA helix by +0.7 °C, but destabilizes DNA helix by -1.6 °C per modification. The apparently hydrophobic formacetal has little effect on hydration of RNA but decreases the hydration of DNA, which suggests that at least part of the difference in thermal stability may be related to differences in hydration. A crystal structure of modified DNA shows that two isolated formacetal linkages fit almost perfectly in an A-type helix (decamer). Taken together, the data suggest that RNA may tolerate nonionic backbone modifications better than DNA. Overall, formacetal appears to be an excellent mimic of phosphate linkage in RNA and an interesting modification for potential applications in fundamental studies and RNA based gene control strategies, such as RNA interference.The potential of RNA interference (RNAi) to become a new therapeutic approach stimulates interest in chemical modifications to optimize the efficacy of RNA-based drugs. 1 Several modifications, developed earlier to improve the properties of antisense oligonucleotides, have also shown promising results in RNAi.1 , 2 We are interested in developing RNA analogues having non-ionic internucleoside linkages.3 ,4 Among such, we have found that replacement of selected phosphates with amide linkages (CH 2 -CO-NH-5′) does not change the overall conformation and thermal stability of RNA. 3 Recently, Iwase et al. 5 reported that introduction of two such amide linkages at the overhanging uridines of an siRNA did not significantly change the RNAi activity. The formacetal linkage 3′-O-CH 2 -O-5′ is another interesting modification that has served as a phosphate mimic in structural studies on a photolyase bound Correspondence to: Eriks Rozners, erozners@binghamton.edu. Supporting Information Available: Experimental procedures, details of thermal melting and osmotic stress experiments, and copies of 1 H and 13 C NMR data. This material is available free of charge via the Internet at http://pubs.acs.org. Previous studies suggested that formacetal modification might have different effect on DNA and RNA oligonucleotides. Van Boom and co-workers found that formacetal modifications strongly destabilized DNA duplexes by -1.4 to -2.4 °C per modification.7 Gao and co-workers reported similar findings (-3 °C per modification), however, their preliminary NMR studies suggested that formacetal linkage caused little structural perturbation of DNA helix.8 Matteucci found that formacetals in the DNA strand only slightly decreased the stability of DNA-RNA heteroduplexes.9 In contrast, our preliminary studies showed that formacetals were somewhat stabilizing in all RNA duplexes (+0.2 to +0.8 °C per modification).4 However, each of these studies used different mo...

Crystallization-induced diastereomer transformations (CIDT) enable isolation of the target compounds in high enantio-and diastereomeric purities and with up to quantitative yields simply by filtration. Numerous inspiring examples of this appealing synthetic strategy reported over the last fifteen years are reviewed. Important observations along with aspects to consider when designing CIDT experiments are discussed. 3.3. Formation of Schiff Base or Related Intermediates 3.4. Aza-Michael and Mannich-Type Reactions 3.5. Strecker Reaction 3.6. Aldol Reactions 3.7. Epimerization at Phosphorus-Based Stereocenters 3.8. Racemization/Epimerization through Change of Conformation 3.9. Miscellaneous Examples of CIDT 4.Conclusions and Perspectives