Alain Valleix

Flexible Synthesis of Pyrimidines with Chiral Monofluorinated and Difluoromethyl Side Chains

Chiral pyrimidines with a fluorine atom in the benzylic position are easily accessible in high enantiomeric excesses from optically active propargylic intermediates by two complementary routes. Both the use of optically active propargylic fluorides and the fluorination of the chiral pyrimidine in the final stage give excellent results in terms of enantiocontrol. On the other hand, original pyrimidines with a difluoromethyl side chain are also obtained in a few steps from new propargylic ketones bearing a CHF(2) substituent on the triple bond.

Enantioselective synthesis of chromenes

A concise approach for the synthesis of optically active chromenes is reported. The process described herein involves, as the key steps, a Sharpless-epoxidation, a selective deoxygenation, and a ring-closing metathesis.

Easy Access to Phosphonothioates

A new and particularly mild method for the formation of phosphorus-sulfur bonds has been achieved through base-catalyzed addition of thiocyanate to the corresponding H-phosphine oxide, phosphinate, or phosphonate. This reaction procedure offers many advantages: the use as starting material of a stable and not oxygen-sensitive phosphorus(v) species, particularly mild and nonaqueous reaction conditions and workup (a pivotal point for these sensitive phosphonothioates), and, through optimized access to thiocyanates, a wider scope of substrates. This method has been applied to achieve the synthesis of substrate analogues for the study of antibody-catalyzed hydrolysis of acetylcholinesterase inhibitor PhX (11).

Total Synthesis of (±)-Halomon by a Johnson–Claisen Rearrangement

The total synthesis of the polyhalogenated antitumour agent halomon (1) was accomplished with two novel transformations as key steps: a Johnson-Claisen rearrangement of a dichlorinated alkene for the preparation of the tertiary chlorinated C3 and a new rearrangement of bromohydrins for the regiospecific introduction of the bromine and chlorine atoms on C6 and C7, respectively.

Design and Synthesis of anα,α-Difluorophosphinate Hapten for Antibody-Catalyzed Hydrolysis of Organophosphorus Nerve Agents

In a new approach to the safe neutralization of organophosphorus chemical weapons, we designed a hapten to elicit catalytic antibodies with phosphatase activity. Here we report the synthesis of this α,α-difluorophosphinate hapten 6. Various methods for the introduction of the key α,α-difluoromethyl feature into the phosphinate hapten are discussed. The best results were obtained with the electrophilic gem-difluorinating agent N-fluorobenzenesulfonimide.

Synthesis and Tritium Labeling of New Aromatic Diazirine Building Blocks for Photoaffinity Labeling and Cross‐Linking

The synthesis of three bifunctional 3-phenyl-3-(trifluoromethyl)diazirinyl building blocks is described. These compounds were designed for their potential chemical reactivity toward a wide range of functional groups occurring in proteins and small molecules. Moreover, we also synthesized the tritiated versions of these three building blocks, using a recently reported chemoselective and regiospecific key-reaction. These building blocks represent a new family of radiolabeled molecules that can be utilized as photoactivatable tags for labeling of proteins or small molecules by using cross-linking or site-directed photoaffinity labeling techniques.

Competitive enzyme immunoassay for urinary vanillylmandelic acid

An enzyme immunoassay for urinary vanillylmandelic acid (VMA) using polyclonal antiserum and VMA-acetylcholinesterase conjugate as enzymatic tracer is described. Two different strategies for immunogen preparation were developed and enantioselectivity was demonstrated. Selected EIA allowed direct measurement of urinary VMA using D(-)-VMA as standard with good sensitivity (MDC = 0.1 mumol/l) and precision (CV less than 7% in 0.2-2.25 mumol/l range). Cross-reactivity with homovanillic acid (HVA) was 0.8% and less than 0.4% with other structurally related catecholamine metabolites. Intra- and inter-assay repeatability were less than 10% and recovery was 97.3% +/- 3%. Good correlation was obtained for EIA and HPLC analysis with normal and pathologic human urine samples (EIA = 0.895 HPLC-7.085, r2 = 0.98, n = 47).

A Powerful Antiradiation Compound Revealed by a New High-Throughput Screening Method

We present a new high‐throughput screening method for the selection of powerful water‐soluble antiradiation compounds. This method, which uses conventional immunoassay techniques, allowed the capacity of a given compound to protect thymidine from irradiation to be evaluated. By applying this assay to an antioxidant library, we showed for the first time that norbadione A, a well‐known mushroom pigment, has pronounced atypical antiradiation properties.

COMPETITIVE IMMUNOASSAY (CAT-EIA), A HELPFUL TECHNIQUE FOR CATALYTIC ANTIBODY DETECTION. PART II

Abstract The Cat-EIA procedure, described in part I, was successfully applied to the screening of 5 different catalytic activities on a given set of 11 mAbs. The precautions required to devoid false-positive identification (preceding paper), were taken into account. Two catalytic activities were thus detected, including a newly thioacetal hydrolysis.

Highly enantioselective synthesis via dynamic kinetic resolution under transfer hydrogenation using Ru(η6-arene)-N-perfluorosulfonyl-1,2-diamine catalysts: a first insight into the relationship of the ligand’s pKa and the catalyst activity

β-(3,4-Dimethoxyphenyl)serine methyl ester was obtained in high diastereomeric and enantiomeric excesses under transfer hydrogenation using chiral Ru(η6-arene)-N-perfluorosulfonyl-1,2-diamine catalysts.