Jean-Pierre Uttaro

A stereocontrolled approach towards highly oxygenated taxane C and CD-ring precursors

Abstract Based upon a remarkable β-face diastereoselection, a stereocontrolled construction of bicyclic systems with the appropriate stereochemical disposition of the substituents belonging either to a Baccatin-I C-ring precursor or a Taxol® CD-ring precursor is reported.

Probing the reactivity of H-phosphonate derivatives for the hydrophosphonylation of various alkenes and alkynes under free-radical conditions

Hydrophosphonylation is an efficient process to create carbon–phosphorus bonds from unsaturated C–C bonds and to give rise to alkylphosphonate or vinylphosphonate derivatives. In this work, we report on the reactivity of H-phosphonate derivatives for the hydrophosphonylation of various alkenes and alkynes under photoinduced free-radical conditions. The reaction was carried out on activated, unactivated and/or disubstituted alkenes or alkynes with 2,2-dimethoxy-2-phenylacetophenone as a photoinitiator under UV irradiation.

Synthesis of the natural enantiomer of neplanocin B

(-)-Neplanocin B, the natural isomer of a component of the neplanocin family was diasteroselectively synthesized from 2,3-O-isopropylidene-D-1,4-ribonolactone. However, when evaluated against several DNA and RNA viruses in cell culture experiments, it did not show any antiviral activity.

Rapid synthesis of carbonucleoside phophonate analogues as potential antiviral agents via a hydrophosphonylation reaction of ethynyl carbocyclic precursors

A racemic synthesis of new carbocyclic nucleoside ethyl or vinylphosphonate analogues bearing purine bases (adenine and guanine) was accomplished using racemic (+/−)-4-O-protected-2-cyclopentanone. All compounds were prepared using a hydrophosphonylation reaction of ethynyl carbocyclic precursors followed by a Mitsunobu coupling reaction between the heterocyclic bases. After deprotection, the compounds were evaluated for their activity against a large number of viruses. However, none of them showed significant antiviral activity or cytotoxicity.

Synthesis of {[5-(adenin-9-yl)-2-furyl]methoxy}methyl phosphonic acid and evaluations against human adenylate kinases.

AMP mimics constitute an important class of therapeutic derivatives to treat diseases where the pool of ATP is involved. A new phosphonate derivative of 9-(5-hydroxymethylfuran-2-yl)adenine was synthesized in a multi-step sequence from commercially available adenosine. Its ability to behave as a substrate of human adenylate kinases 1 and 2 was assessed. The phosphonate was shown to be a moderate but selective substrate of the mitochondrial human AK2, better than well-known antiviral acyclic phosphonates 9-(2-phosphonomethoxyethyl)adenine (PMEA, Adefovir) and (R)-9-(2-phosphonomethoxypropyl)adenine (PMPA, Tenofovir). Putative binding mode within adenylate kinase NMP site revealed by molecular docking in comparison to AMP native substrate allowed to illustrate this selective behavior.

First enantioselective synthesis of (–)-neplanocin B

(-)-Neplanocin B, the natural isomer of a component of the neplanocin family was enantioselectively synthesized.