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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 radical allylation of a series of α-halo or α-phenylseleno-β-alkoxy esters in the presence of MgBr2·OEt2 is reported and compared with analogous reactions under non-chelating conditions. The addition of MgBr2·OEt2 gives excellent selectivity favoring anti products; in some cases ratios >100:1 are obtained. Varying the substrate substituents reveals that these reactions are quite tolerant of alkyl functionalities at the β-position. Changes to the alkoxy function indicate that a chelate is involved in the reaction. The reactions are successful with secondary iodides, bromides, and phenylselenides, as well as tertiary iodides, which all give very high ratios under chelation control. Performing less well under the same conditions are substrates with a radical exocyclic to a tetrahydrofuran ring. EDTA titration is used to determine the amount of Mg2+ dissolved in the allylation reaction mixture, and 13C NMR is employed to better define the nature of the complex formed (chelate or monodentate) prior to the reaction. Competition experiments suggest that the chelate and monodentate pathways are in competition for the radical allylation with allyltributyltin.Key words: allylation, radicals, Lewis acid, stereoselectivity, 1,2-induction.

Dimethylboron bromide or diphenylboron bromide can be used in combination with borane to achieve the regiocontrolled conversion of benzylidene acetals to their corresponding hydroxy benzyl ethers with moderate to high yields. Keywords: dimethylboron bromide, diphenylboron bromide, reductive opening, benzylidene, acetals.

The construction of the 15-carbon chiral framework of erythronolide A is described, based on a synthetic strategy that uses carbohydrate-derived 'chiral templates' as prefabricated segments of the target molecule.

Using C-furanosides as chiral precursors of (Z,E) 1,3-dienes has permitted the synthesis of two leukotriene B4 analogues: 3-thia-LTB4 and 3-thia-20,20,20-trifluoro-LTB4.