Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6 -dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

Iodination of carbohydrate-derived 3,6-dihydro-2H-1,2-oxazines of type 3 using iodine and pyridine in DMF furnished 5-iodo-substituted 1,2-oxazine derivatives 4 with high efficacy. The alkenyl iodide moiety of 1,2-oxazine derivatives syn-4 and anti-4 was subsequently exploited for the introduction of new functionalities at the C-5 position by applying palladium-catalyzed carbon–carbon bond-forming reactions such as Sonogashira, Heck, or Suzuki coupling reactions as well as a cyanation reaction. These cross-coupling reactions led to a series of 5-alkynyl-, 5-alkenyl-, 5-aryl- and 5-cyano- substituted 1,2-oxazine derivatives being of considerable interest for further synthetic elaborations. This was exemplarily demonstrated by the hydrogenation of syn-21 and anti-24 and by a click reaction of a 5-alkynyl-substituted precursor

Synthesis and Properties of 6′-Fluoro-tricyclo-DNA

The synthesis of the two fluorinated tricyclic nucleosides 6?-F-tc-T and 6?-F-tc-5MeC, as well as the corresponding building blocks for oligonucleotide assembly, was accomplished. An X-ray analysis of N4-benzoylated 6?-F-tc-5MeC reavealed a 2?-exo (north) conformation of the furanose ring, characterizing it as an RNA mimic. In contrast to observations in the bicyclo-DNA series, no short contact between the fluorine atom and the H6 of the base, reminiscent of a nonclassical F···H hydrogen bond, could be observed. Tm measurements of modified oligodeoxynucleotides with complementary RNA showed slightly sequence-dependent duplex stabilization profiles with maximum ?Tm/mod values of +4.5 °C for 6?-F-tc-5MeC and +1 °C for 6?-F-tc-T. In comparison with parent tc-modified oligonucleotides, no relevant changes in Tm were detected, attributing the fluorine substituent a neutral role in RNA affinity. A structural analysis of duplexes with DNA and RNA by CD-spectroscopy revealed a shift from B- to A-type conformation induced by the 6?-F-tc-nucleosides. This is not a specific ?fluorine effect?, as the same is also observed for the parent tc-modifications. The two fluorinated tc-nucleosides were also incorporated into a pure tricyclo-DNA backbone and showed no discrimination in Tm with complementary RNA, demonstrating that 6?-F substitution is also compatible within fully modified tc-oligonucleotides

2′-Fluorination of Tricyclo-DNA Controls Furanose Conformation and Increases RNA Affinity

The synthesis of 2′-fluoro tricyclo-DNA pyrimidine nucleosides with fluorine in the ribo-configuration and their incorporation into oligodeoxynucleotides was accomplished. Unlike the parent tc-T nucleoside, the 2′F-RNA-tc-T unit occurs in the 2′-exo conformation in the crystal. Specifically, F-RNA-tc-T was found to stabilize duplexes with RNA by +2 to +4 °C in <i>T</i>_m/mod. F-RNA-tc-nucleosides mix well with the DNA backbone and thus open up possibilities of using shorter and mixed-(DNA/tc-DNA) backbone oligonucleotides for therapeutic applications

Synthesis and Properties of 6′-Fluoro-tricyclo-DNA

The synthesis of the two fluorinated tricyclic nucleosides 6′-F-tc-T and 6′-F-tc-5^MeC, as well as the corresponding building blocks for oligonucleotide assembly, was accomplished. An X-ray analysis of N⁴-benzoylated 6′-F-tc-^5MeC reavealed a 2′-exo (north) conformation of the furanose ring, characterizing it as an RNA mimic. In contrast to observations in the bicyclo-DNA series, no short contact between the fluorine atom and the H6 of the base, reminiscent of a nonclassical F···H hydrogen bond, could be observed. <i>T</i>_m measurements of modified oligodeoxynucleotides with complementary RNA showed slightly sequence-dependent duplex stabilization profiles with maximum Δ<i>T</i>_m/mod values of +4.5 °C for 6′-F-tc-^5MeC and +1 °C for 6′-F-tc-T. In comparison with parent tc-modified oligonucleotides, no relevant changes in <i>T</i>_m were detected, attributing the fluorine substituent a neutral role in RNA affinity. A structural analysis of duplexes with DNA and RNA by CD-spectroscopy revealed a shift from B- to A-type conformation induced by the 6′-F-tc-nucleosides. This is not a specific “fluorine effect”, as the same is also observed for the parent tc-modifications. The two fluorinated tc-nucleosides were also incorporated into a pure tricyclo-DNA backbone and showed no discrimination in <i>T</i>_m with complementary RNA, demonstrating that 6′-F substitution is also compatible within fully modified tc-oligonucleotides

Applications of Modern Technologies in the Production of Aircraft Propeller Prototype

In the field of engineering relatively new designs and manufacturing processes are constantly emerging. These changes are often seen in designing and manufacturing of prototypes or in single part production. We decided to analyse an aircraft propeller prototype using modern technologies. Existing aircraft blade design was converted to digital models which were analysed