The improvement in fluorescence properties of 2′-deoxyuridine was made possible by the introduction of (hetero)aromatic moieties at the C–5 position of uridine with alkenyl/phenyl/styryl linkers to create a library of useful fluorescent nucleosides.

Stille cross-coupling reactions with its unique reactivity and milder reaction conditions have provided researchers with a useful synthetic alternative compared to the conventional methods of synthesis for modified nucleosides. The examples presented in this chapter also highlight the usefulness of the catalytic process.

In the asymmetric unit, equalling the unit cell (triclinic, P 1, Z = 1), two molecules of the title compound, 8-(4-methylphenyl)-D-2′-deoxyadenosine, C 17 H 19 N 5 O 3 , are present, with distinct conformations of the two sugar moieties, together with one solvent water molecule. All three ribose O atoms are involved in hydrogen bonding and the crystal packing is largely determined by hydrogen-bonding or hydrogen–heteroatom interactions (O—H...O, O—H...N, N—H...O, C—H...O and C—H...N) with one independent molecule directly linked to four neighbouring molecules and the other molecule directly linked to six neighbouring molecules. The two independent molecules of the asymmetric unit display three weak intramolecular C—H-to-heteroatom contacts, two of which are very similar despite the different conformations of the deoxyribosyl moieties. The aromatic ring systems of both molecules are in proximity to each other and somehow aligned, though not coplanar. The absolute structures of the two molecules were assumed with reference to the reactant 8-bromo-D-2′-deoxyadenosine as they could not be determined crystallographically.

In the asymmetric unit, equalling the unit cell (triclinic, P1, Z = 1), two mol-ecules of the title compound, 8-(4-methyl-phen-yl)-d-2'-de-oxy-adenosine, C17H19N5O3, are present, with distinct conformations of the two sugar moieties, together with one solvent water mol-ecule. All three ribose O atoms are involved in hydrogen bonding and the crystal packing is largely determined by hydrogen-bonding or hydrogen-heteroatom inter-actions (O-H⋯O, O-H⋯N, N-H⋯O, C-H⋯O and C-H⋯N) with one independent mol-ecule directly linked to four neighbouring mol-ecules and the other mol-ecule directly linked to six neighbouring mol-ecules. The two independent mol-ecules of the asymmetric unit display three weak intra-molecular C-H-to-heteroatom contacts, two of which are very similar despite the different conformations of the deoxyribosyl moieties. The aromatic ring systems of both mol-ecules are in proximity to each other and somehow aligned, though not coplanar. The absolute structures of the two mol-ecules were assumed with reference to the reactant 8-bromo-d-2'-de-oxy-adenosine as they could not be determined crystallographically.

In the asymmetric unit, equalling the unit cell (triclinic, P1, Z = 1), two mol­ecules of the title compound, 8-(4-methyl­phen­yl)-d-2′-de­oxy­adenosine, C17H19N5O3, are present, with distinct conformations of the two sugar moieties, together with one solvent water mol­ecule. All three ribose O atoms are involved in hydrogen bonding and the crystal packing is largely determined by hydrogen-bonding or hydrogen–heteroatom inter­actions (O—H⋯O, O—H⋯N, N—H⋯O, C—H⋯O and C—H⋯N) with one independent mol­ecule directly linked to four neighbouring mol­ecules and the other mol­ecule directly linked to six neighbouring mol­ecules. The two independent mol­ecules of the asymmetric unit display three weak intra­molecular C—H-to-heteroatom contacts, two of which are very similar despite the different conformations of the deoxyribosyl moieties. The aromatic ring systems of both mol­ecules are in proximity to each other and somehow aligned, though not coplanar. The absolute structures of the two mol­ecules were assumed with reference to the reactant 8-bromo-d-2′-de­oxy­adenosine as they could not be determined crystallographically.

A broadly applicable catalyst system consisting of water-soluble Pd--imidate complexes has been enployed for the Suzuki-Miyaura cross-coupling of four different nucleosides in water under mild conditions. The efficient nature of the catalyst system also allowed its application in developing a microwave-assisted protocol with the purpose of expediting the catalytic reaction. Preliminary mechanistic studies, assisted by catalyst poison tests and stoichiometric tests performed using an electrospray ionization spectrometer, revealed the possible presence of a homotopic catalyst system.

The synthesis of a highly efficient, water soluble [Pd(Sacc)2 (TPA)2 ] complex for C-C bond formation is described. Additionally, application of the [Pd(Sacc)2 (TPA)2 ] complex for Suzuki-Miyaura arylation of all four nucleosides (5-iodo-2'-deoxyuridine [5-IdU], 5-iodo-2'-deoxycytidine [5-IdC], 8-bromo-2'-deoxyadenosine, and 8-bromo-2'-deoxyguanosine) with various aryl/heteroaryl boronic acids in plain water under milder conditions is demonstrated. © 2016 by John Wiley & Sons, Inc.

Two new water-soluble phosphatriazene as versatile ligands for catalyzing Suzuki–Miyaura reactions of purines and pyrimidines in neat water with the possibility of recycling. Copper-free Sonogashira and Heck reaction were also made possible.

AbstractThe new approach is used for the highly efficient scale‐up synthesis of the HSV‐1 inhibitor Brivudine (BVDU) (IV).

Subtle modulation of the electronic properties of the dibenzylideneacetone (dba) ligand allows the development of an efficient protocol for the Heck alkenylation of 5-iodo-2′-deoxyuridine. This protocol enables the large-scale synthesis of commercially important nucleoside building blocks. The isolation of one key molecule was accomplished under column-free conditions on a 10-gram scale.

Pd–imidate complexes as recyclable catalysts for Heck alkenylation of pyrimidine nucleosides. Pd–imidate complexes have been employed as efficient catalysts for the Heck alkenylation of unprotected 5-iodo-2′-deoxyuridine in acetonitrile.

The direct reactions between the precursors trans-[Pd(Imidate)2(SMe2)2] and 1,3,5-triaza-7-phosphaadamantane (PTA) yield new water-soluble palladium(II) complexes trans-[Pd(Imidate)2(PTA)2]. These new complexes have revealed as excellent catalysts for environmentally friendly, efficient cross-coupling of synthetically challenging substrates like the antiviral nucleosides in neat water as solvent. Besides this our research group has also been interested in the development of industrially feasible (column-free) scale-up processes for the synthesis of modified nucleosides having commercial relevance.