Martin Kullberg

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.

Nucleoside H-phosphonates. Part 19: Novel nucleotide analogues-H-phosphonoselenoate mono- and diesters

Abstract Efficient protocols for the preparation of novel synthetic intermediates, H-phosphonoselenoate monoesters and the corresponding dinucleoside H-phosphonoselenoate diesters, have been developed.

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.

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.

9-Fluorenemethyl H-Phosphonoselenoate—A Versatile Reagent for Transferring an H-Phosphonoselenoate Group

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

Developing Synthetic Methods for Bioactive Phosphorus Compounds Using H-Phosphonate Chemistry: A Progress Report

Abstract 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.

Nucleoside H-Phosphonates XX. Efficient Method for the Preparation of Nucleoside H-Phosphonoselenoate Monoesters

In this thesis, the chemistry of compounds containing P-Se bonds has been studied. As a new addition to this class of compounds, H-phosphonoselenoate monoesters, have been introduced and two synthetic pathways for their preparation have been developed.The reactivity of H-phosphonoselenoate monoesters towards a variety of condensing agents has been studied. From these, efficient conditions for the synthesis of H-phosphonoselenoate diesters have been developed. The produced diesters have subsequently been used in oxidative transformations, which gave access to the corresponding P(V) compounds, e.g. dinucleoside phosphoroselenoates or dinucleoside phosphoroselenothioates.Furthermore, a new selenizing agent, triphenyl phosphoroselenoate, has been developed for selenization of P(III) compounds. This reagent has high solubility in organic solvents and was found to convert phosphite triesters and H-phosphonate diesters efficiently into the corresponding phosphoroselenoate derivatives.The selenization of P(III) compounds with triphenyl phosphoroselenoate proceeds through a selenium transfer reaction. A computational study was performed to gain insight into a mechanism for this reaction. The results indicate that the transfer of selenium or sulfur from P(V) to P(III) compounds proceeds most likely via an X-philic attack of the P(III) nucleophile on the chalcogen of the P(V) species. For the transfer of oxygen, the reaction may also proceed via an edge attack on the P=O bond.