Monomers for preparation of amide linked RNA: Synthesis of C3'-homologated nucleoside amino acids from d-xylose.

Amides as neutral and hydrophobic internucleoside linkages in RNA are highly interesting modifications for RNA interference. However, testing amides in siRNAs is hampered by the shortage of efficient methods to synthesize the monomeric building blocks, the nucleoside amino acid equivalents. This paper reports an efficient synthesis of protected ribonucleoside 5'-amino 3'-carboxylic acids from d-xylose in 14 steps 7% overall yield. The key features that ensure efficiency and ease of operations are chemoselective reduction of the ester and minimization of protecting group manipulation.

Highly enantioselective organocatalytic addition of aldehydes to N-(Phenylmethylene)benzamides: asymmetric synthesis of the paclitaxel side chain and its analogues.

Easily side-tracked: A simple route to the paclitaxel side chain and its analogues is based on the (R)-proline-catalyzed addition of aldehydes to N-(phenylmethylene)benzamides, followed by oxidation of the resulting protected alpha-hydroxy-beta-benzoylaminoaldehydes (92-99 % ee). Esterification of the subsequent phenylisoserine derivatives with baccatin III gives paclitaxel analogues (see scheme).A simple highly enantioselective organocatalytic addition of aldehydes to N-(phenylmethylene)benzamides is presented. The application of (R)-proline as the catalyst and subsequent oxidation of the protected alpha-hydroxy-beta-benzoylaminoaldehydes (92-99 % ee) gives access to esterification-ready phenylisoserine derivatives such as the protected paclitaxel (taxol) side chain. Esterification of these derivatives with baccatin III gives access to the cancer chemotherapeutic substance paclitaxel and its analogues that do not exist in nature.

Probing binding requirements of NAD kinase with modified substrate (NAD) analogues.

Synthesis of novel NAD(+) analogues that cannot be phosphorylated by NAD kinase is reported. In these analogues the C2' hydroxyl group of the adenosine moiety was replaced by fluorine in the ribo or arabino configuration (1 and 2, respectively) or was inverted into arabino configuration to give compound 3. Compounds 1 and 2 showed inhibition of human NAD kinase, whereas analogue 3 inhibited both the human and Mycobacterium tuberculosis NAD kinase. An uncharged benzamide adenine dinucleotide (BAD) was found to be the most potent competitive inhibitor (K(i)=90 microM) of the human enzyme reported so far.

Developing synthetic methods for bioactive phosphorus compounds using H-phosphonate chemistry: a progress report.

In this paper a short account of our recent basic studies aiming toward development of new synthetic methods for the preparation of nucleotide analogues using H-phosphonate chemistry is presented.

Oxidative transformations of nucleoside fluorenemethyl H-phosphonoselenoate diesters.

9-Fluorenemethyl H-phosphonoselenoate monoester has been used to produce thymidine 3'-O-phosphoroselenoate monoester from which various P(V) derivatives containing multiple modifications at phosphorus were obtained; e.g., thymidine 3'-O-phosphoroselenofluoridate, 3'-O-phosphoroselenothioate, or 3'-O-phosphorodiselenoate monoesters.

Preparation of nucleoside H-phosphonoselenoate monoesters via the phosphinate approach.

An efficient entry to nucleoside 3'-H-phosphonoselenoate monoesters via phosphinate intermediates was developed. It involves a reaction of suitably protected nucleosides with triethylammonium phosphinate in the presence of pivaloyl chloride, followed by selenization of the intermediate nucleoside phosphinates with triphenylphosphine selenide, to produce the corresponding nucleoside H-phosphonoselenoates in 86-92% yields.

Developing synthetic methods for bioactive phosphorus compounds using H-phosphonate chemistry: a progress report.

In this paper a short account of our recent research concerning the development of new synthetic methods and reagents for the preparation of nucleotides and their analogues, is given.

9-Fluorenemethyl H-phosphonoselenoate--a versatile reagent for transferring an H-phosphonoselenoate group.

This paper expands the available methods for preparation of H-phosphonoselenoate using a new reagent, 9-fluorenemethyl H-phosphonoselenoate.