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An acyclic approach to synthesize thiofuranoside N-glycosides bearing an adenine nucleobase is presented herein. This approach provides a significant improvement in terms of regio- and diastereoselectivity compared with the current paradigms used for their formation. Activation of acyclic dithioacetal substrates bearing either a C2′-alkoxy or fluoro group and coupling with purine nucleobases selectively generates 1′,2′-syn thioaminals. The regiochemistry of the nucleobase coupling (N7 or N9) can also be controlled by using either silylated or unsilylated purines. A subsequent SN2-like cyclization of these 1′,2′-syn acyclic thioaminals results in the desired 1′,2′-cis thionucleoside analogues.

The progress towards the development of a nucleoside analogue with inhibitory properties against SETDB1, a histone methyltransferase (HMT), is described. Based on the structure of the natural cofactor S-adenosyl-L-methionine (SAM), novel fluorinated nucleoside analogues were synthesized. Two of these compounds bearing a C2′-F and C5′-primary amine moiety showed moderate inhibition of SETDB1, a lysine HMT for which there is only one reported inhibitor.

The synthesis of novel nucleoside analogues bearing a C3′ all-carbon quaternary center and a C2′-hydroxy substituent is described. The all-carbon stereogenic center was generated through an intramolecular 7-endo attack of a silyl-tethered allyl moiety on a tertiary radical using photoredox catalysis. Subsequent allylic oxidation and diastereoselective hydride reductions provided the hydroxy substituent at C2′, which then controls the stereoselective introduction of pyrimidine nucleobases on the corresponding furanose scaffold. Density functional theory (DFT) calculations provided insights into the origin of the high syn diastereoselectivity resulting from the radical cyclization. This original methodology grants access to a wide range of 1′,2′-cis and 1′,2′-trans arabino- and ribo-like analogues bearing an all-carbon quaternary center at C3′. These molecules are currently being tested for their antiviral and anticancer properties.

The design of novel nucleoside analogues bearing a C2' all-carbon quaternary center is described. The construction of this all-carbon stereogenic center involves the use of photoredox catalysis to initiate an intramolecular attack of a silyl-tethered vinyl functionality on a tertiary radical. Density functional theory calculations were performed to explore the origin of the high syn diastereoselectivity obtained through the preferred 5-exo-trig cyclization mode. The intramolecular vinyl addition also enables the preparation of the complementary configuration of the C2' all-carbon stereocenter when performed after lactonization.

Nucleoside analogues bearing a fluorine in the C2′-position have been synthesized by SN2-like cyclizations of acyclic thioaminal precursors. This strategy provides access to two scaffolds, d-1′,2′-cis-thiofuranosides and d-1′,2′-trans-furanosides, which are difficult to generate using the standard approach for nucleoside synthesis. The addition of silylated nucleobases onto model C2-fluorinated dithioacetal substrates resulted in 1,2-syn diastereoselectivity, which is consistent with the C2–F and S-alkyl moiety being in close proximity. A new series of analogues bearing a C3′ all-carbon quaternary center along with a C2′–F atom have also been synthesized using this approach and are being investigated as potential antimetabolites.

A synthetic strategy to access a novel family of nucleoside analogues bearing a C3'-nitrile substituted all-carbon quaternary center is presented herein. These purine bearing scaffolds were tested in two pancreatic cancer cell lines harboring either wild-type (BxPC3) or G12V KRAS (Capan2) mutations. A promising compound was shown to have significantly greater efficacy in the Capan2 cell line as compared to Gemcitabine, the clinical gold standard used to treat pancreatic cancer.

Reported herein is an experimental and theoretical study that elucidates why silylated nucleobase additions to acyclic α-alkoxythiacarbenium intermediates proceed with high 1,2-syn stereocontrol (anti-Felkin-Anh), which is opposite to what would be expected with corresponding activated aldehydes. The acyclic thioaminals formed undergo intramolecular cyclizations to provide nucleoside analogues with anticancer and antiviral properties. The factors influencing the selectivity of the substitution reaction have been examined thoroughly. Halothioether species initially form, ionize in the presence (low dielectric media) or absence (higher dielectric media) of the nucleophile, and react through SN2-like transition structures (TS A and D), where the α-alkoxy group is gauche to the thioether moiety. An important, and perhaps counterintuitive, observation in this work was that calculations done in the gas phase or low dielectric media (toluene) are essential to locate the product- and rate-determining transition structures (C-N bond formation) that allow the most reasonable prediction of selectivity and isotope effects for more polar solvents (THF, MeCN). The ΔΔG(⧧) (G(TSA-TSD)) obtained in silico are consistent with the preferential formation of 1,2-syn product and with the trends of stereocontrol displayed by 2,3-anti and 2,3-syn α,β-bis-alkoxydithioacetals.

The design of a novel nucleoside scaffold that exhibits an all-carbon quaternary center is reported. This allows for both α- and β-anomers of a given 2'-deoxy-2',2'-difluoro nucleoside analog (NA) to have potential biological activity. Using an intramolecular atom-transfer reaction, an all-carbon quaternary center was obtained without the use of heavy metals and/or harsh conditions. The chemistry developed is efficient, easily scalable and leads to novel libraries of molecules.

Reported herein is a novel and versatile strategy for the stereoselective synthesis of unnatural β-L-arabinofuranosyl nucleoside analogues from acyclic N,OTMS-acetals bearing pyrimidine and purine bases. These unusual acetals undergo a C1' to C4' cyclization where the OTMS of the acetal serves as the nucleophile to generate 2'-oxynucleosides with complete retention of configuration at the C1' acetal center. N,OTMS-acetals are obtained diastereoselectively from additions of silylated nucleobases onto acyclic polyalkoxyaldehydes in the presence of MgBr(2)·OEt(2). The strategy reported is addressing important synthetic challenges by providing stereoselective access to unnatural L-nucleosides starting from easily accessible pools of D-sugars and, as importantly, by allowing the formation of the sterically challenging 1',2'-cis nucleosides. A wide variety of nucleoside analogues were synthesized in 7-8 steps from easily accessible D-xylose.

Silicon carbide thin films have been deposited via sublimation of a solid organosilane polymer source using atmospheric pressure chemical vapour deposition process (PS-CVD). The advantages of this new process include high deposition rate, compatibility with batch process, hazard-free working environment and low deposition cost. The silicon carbide (SiC) thin films obtained through this process exhibit a highly uniform film thickness, highly conformal coating, and very high chemical resistance to acids and alkaline solutions. These characteristics make the SiC thin films obtained by PSCVD process very attractive as a structural material for micro-electro-mechanical systems (MEMS) and as a coating film in a wide range of other applications. These SiC thin films are also expected to be attractive as a semiconductor material provided that the defects, oxygen and nitrogen contaminations can be reduced and effectively controlled. In this work we have investigated the chemical, structural, electrical and optical properties of these films, using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), elastic recoil detection spectroscopy (ERD), ultraviolet-visible photospectroscopy (UV-Vis), ellipsometry, and capacitance-voltage measurements (C-V).

This paper presents the creation of a template for the interpretation and simulation of second order AA'XX' NMR-spectra, starting from the core information offered in a regular undergraduate physical chemistry course.

The electro-optical properties of SiONC dielectric thin films deposited by polymer-source chemical vapor deposition using an organosilane precursor has been investigated as a function of oxygen concentration in the films. SiONC thin films were characterized using capacitance-voltage (C-V), conductance-voltage (G-V), ellipsometry, and ultraviolet visible (UV-Vis) photospectroscopy. These measurements showed that the electro-optical properties of the films are greatly influenced by the atomic concentration of oxygen. The high frequency C-V measurement revealed a nearly ideal metal-oxide-semiconductor (MOS) structure behavior at high atomic concentration of oxygen (35 at. %). A relative dielectric constant as high as 6 is obtained at 10 kHz for samples with about 5 at. % of oxygen, which corresponds to high-k dielectric material. The interface trap density extracted from G-V measurement using Hill-Coleman method is as low as 3.2×1010 (cm−2 eV−1), making these films a viable high-k dielectric alternative to S...

Thin films of silicon oxynitrocarbide (SiONC) have been deposited on silicon by polymer-source chemical vapor deposition (PSCVD) using poly(dimethylsilane). The chemical and structural composition of these films have been investigated using Fourier transform infrared spectroscopy, elastic recoil detection spectroscopy (ERD), and X-ray photoelectron spectroscopy (XPS). ERD depth-profile analysis revealed a homogeneous film with uniform bulk concentrations for silicon, carbon, nitrogen, and oxygen. XPS analysis showed that nitrogen, oxygen, and carbon were all uniquely bonded to silicon. The oxygen nitrogen bonds were not observed in these films. XPS analysis also revealed the presence of carbon-carbon bonds associated with graphite. It was shown that the graphitic phase is limited to the surface layer of these films, and is due to unintentional carbonization at the end of the deposition process. The relatively low bulk atomic concentration of carbon in the SiONC thin films (∼ 1%) render these films a possible alternative to SiON, and could become very attractive for the fabrication of integrated optical waveguides, and as a dielectric material in variety of microelectronic and optoelectronic devices.