Angela M. Bernard

Very high stereoselectivity in organocatalyzed desymmetrizing aldol reactions of 3-substituted cyclobutanones

N-Phenylsulfonyl (S)-proline catalyzes the direct aldol reaction of 3-substituted cyclobutanones and aryl aldehydes in good yield and with excellent diastereoselectivity and enantioselectivity. This desymmetrization process provides highly functionalized cyclobutanones with control over three contiguous stereogenic centers.

Addition of 1,3-Benzoxathiole 3-Oxide Anion to Azomethines under Varying Reaction Conditions

The reaction of benzoxathiole 3-oxide with LDA in THF gave an anion which was reacted with azomethines under varying conditions of temperature and solvent. At −78 °C in THF, the two diastereomers resulting from a trans addition were mainly obtained, while at temperatures higher than −40 °C, or upon increasing the solvent polarity, only one trans and one cis diastereomer were obtained. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synthesis of Tertiary Cyclobutanols through Stereoselective Ring Expansion of Oxaspiropentanes Induced by Grignard Reagents

Abstract The stereoselectivity of the ring expansion of oxaspiropentanes to cyclobutanols induced by Grignard reagents has been studied. It has been found that the reaction occurs through the intermediacy of a cyclobutanone, formed stereospecifically, whereas the attack of the Grignard reagent on the carbonyl group of the cyclobutanone is stereospecific only in the case of the oxaspiropentanes derived from aldehydes.

Palladium (0) Catalyzed Nucleophilic Substitution On 2-Cyclopropylidene-phenoxy Ethanes

Abstract 2-cyclopropylidene-phenoxy ethanes 5, 2-substituted with alkyl, aryl or heterocyclic groups are readily obtained in high yields by the Wittig reaction of the easily accessible α-phenoxy etanones 4 with (3-bromo propyl) triphenylphosphonium bromide. They react with complete regioselectivity in palladium (0) catalyzed nucleophilic substitutions with a series of soft carbon nucleophiles giving an easy entry to 5,6-methanoamino acids.

Mechanism of decarbalkoxylation of arylmethylene-propanedioic acid dimethyl esters

Abstract The decarbalkoxylation in DMSO-NaX-H2 O, of some arylmethylene propanedioic acid dimethyl esters is studied. Both the relative rates of the para (R = NO2, H, CH3, OCH3) and the ortho [R = H, OCH3 , OCH(CH3)2]substituted aryl derivatives, together with the stereochemical outcome, support a preliminary nucleophilic attack by water followed by decarbalkoxylative elimination.

A new entry to alkylidenecyclopropanes through a Ramberg-Backlund rearrangement of cyclopropylsulfones

Abstract The first use of the Ramberg-Backlund rearrangement of cyclopropylsulfones in the synthesis of alkylidenecyclopropanes is reported.

Synthesis of new compounds with promising antiviral properties against group A and B Human Rhinoviruses

The human common cold, which is a benign disease caused by the Rhinoviruses, generally receives palliative symptomatic treatments, since no specific therapy against any of these viruses currently exists. In this work, some original synthetic compounds were produced and tested, in order to find non-toxic substances with an improved protection index (PI) for infected cells, as compared to reference drugs such as Pirodavir. We designed a series of novel molecules with a double oxygen in the central hydrocarbon chain and some modifications of the lateral methylisoxazole and propoxybenzoate moieties of lead compound 6602 (ethyl 4-{3-[2-(3-methyl-1,2-isoxazol-5-yl)ethoxy]propoxy}benzoate). It was found that most of these substances were actually less toxic than Pirodavir; in addition, the new molecule indicated as 8c was more than 30 times less toxic than Pirodavir, about twice as active on the group A strain of Rhinovirus HRV14, and even four times more effective on the group B strain HRV39, as compared to Pirodavirs PI.

Easy access to trans-2,3-disubstituted cyclobutanones, 2,4,5-trisubstituted 3,6-dihydro-2H-pyrans and cis-substituted phenylcyclopropylsulfones by using the highly versatile 1-phenylsulfenyl- or 1-phenylsulfonyl-cyclopropylketones

The high versatility of 1-phenylsulfenyl- or 1-phenylsulfonyl-cyclopropylketones has been exploited for the regioselective synthesis of trans-2,3-disubstituted cyclobutanones, 2,4,5-trisubstituted 3,6-dihydro-2H-pyrans and cis-2-alkyl- or cis-2-aryl-cyclopropylphenylsulfones.

Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds

Background The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication. Methods These compounds were explored for in vitro antiviral potential on other human pathogenic Enteroviruses, namely Enterovirus 71 on rhabdo-myosarcoma cells, Coxsackievirus B3 on Vero cells, Poliovirus 1 and Echovirus 11 on BGM cells. Results Activity was confirmed for compound against Rhinovirus 14. Furthermore, few compounds showed a cell-protective effect on Enterovirus 71, presented a marked improvement as compared to the reference drug pleconaril for inhibitory activity on both Enterovirus 71 and Poliovirus 1. The most striking observation was the clear cell protective effect for the set of analogues in a virus-cell-based assay for Echovirus 11 with an effective concentration (EC50) as low as 0.3 µM (Selectivity index or SI = 483), and selectivity indexes greater than 857 (EC50 = 0.6 µM) and 1524 (EC50 = 0.33 µM). Conclusion Some of the evaluated compounds showed potent and selective antiviral activity against several enterovirus species, such as Enterovirus 71 (EV-A), Echovirus 11 (EV-B), and Poliovirus 1 (EV-C). This could be used as a starting point for the development of other pleconaril/pirodavir-like enterovirus inhibitors with broad-spectrum activity and improved effects as compared to the reference drugs.

Stereochemistry of decarbalkoxylation of arylmethylene-propanedioic acids dimethyl esters

Abstract Halide ions increase the rate of decarbalkoxylation of arylmethylene-propanedioic acids dimethyl esters.