Sergio Pucci

Pyrazolothiazolopyrimidine derivatives as a novel class of anti-inflammatory or antinociceptive agents: synthesis, structural characterization and pharmacological evaluation☆

Abstract As a part of a research program on anti-inflammatory-analgesic compounds, pyrazolothiazolopyrimidines 5a-f and 5g-i were prepared by cyclodehydration in 98% H 2 SO 4 or PPA of the corresponding 6-thioketomethylene-substituted-4-hydroxy-pyrazolo[3,4- d ]pyrimidines 2a-i and 2g-i . The results of the pharmacological in vivo screening indicate an interesting dissociation of the analgesic from the anti-inflammatory activity depending on aromatic or aliphatic substitution at the C4 of the thiazole ring. Analgesic activity was not associated with any narcotic effect; in addition, all the active compounds showed a remarkable systemic and gastric tolerance. This indicated a mode of action different from that of the classical nonsteroidal anti-inflammatory drugs, acting on prostaglandin biosynthesis. To clarify the mechanism or the mechanisms underlying the pharmacological activity of these and other closely related compounds, we initiated a ‘file chemical approach’ to various systems involved in the inflammatory process. At present, some of the more active in vivo compounds tested as substance P antagonists showed a moderate and possibly non-specific effect on NK 1 and NK 2 receptors.

Rhodium catalyzed deuteroformylation of styrene: (E)- and (Z)-β-deuterostyrene and β,β-dideuterostyrene formation via selective β-hydride elimination from the branched alkylrhodium intermediate

Deuteroformylation of styrene in the presence of Rh4(CO)12 as a catalytic precursor was carried out at 160 atm of CO and D2 1/1 at two temperatures (20 and 90°C) and for times yielding partial or complete conversion. Compounds recovered from the mixture produced by reaction and partial conversion at 90°C include unlabeled styrene, (E)- and (Z)-β-deuterostyrene, C6H5CHCHD, and β,β-dideuterostyrene, C6H5CHCD2, whereas at room temperature the styrene does not take up deuterium. These results indicate that under hydroformylation conditions the branched alkylrhodium intermediate, which affords the branched aldehyde, in part dissociates into rhodium hydride and deuterated olefin. By contrast the linear alkyl intermediate does not dissociate under the same conditions, but instead yields almost completely the corresponding aldehyde.

A simple method for the extraction of volatile organic compounds contained in air samples from adsorbent materials by solid phase microextraction and their analysis by gas chromatography/mass spectrometry

The monitoring of air pollution requires simple, rapid and sensitive sampling and analytical techniques with minimal sample manipulation that are usable for routine analyses. In our laboratories we have developed a method for the analysis of air samples collected by adsorbent cartridges based on solid phase microextraction (SPME) coupled to gas chromatography/mass spectrometry. We investigated the influence of some variables (time and temperature) using toluene as analyte (one of the most common air pollutants) and toluene-d(8) on the SPME extraction, and the sensitivity (LOQ) of the method. We then tested the method on an air sample collected in an industrial area and carried out characterisation of the volatile organic compounds present.

Diastereoselectivity in the rhodium-catalyzed hydroformylation of (+)(R)-1-phenylethyl vinyl ether

Abstract The degree of diastereoselectivity in the rhodium-catalyzed hydroformylation of (+)( R )-1-phenylethyl vinyl ether is much higher than that in the hydroformylation of the related olefin, 4-phenyl-1-pentene.

Unforeseen alkylating effect of triethylorthoformate in the synthesis of pyrazolotriazolopyrimidine derivative

Summary The final ring closure reaction of 2-phenylamino-3-aminopyrazolo[3,4- d ]pyrimidin-4-ones with triethylorthoformate in the synthesis of 1 H -pyrazolo[3,4- d ][1,2,4]-8 H -triazolo[2,3- a ]-4 H -pyrimidin-4-one derivatives, unexpectedly gave both the desired product and its N 2 -ethyl analog. The structure of the latter, which arises from an unexpected alkylating effect of triethylorthoformate, was determined through a combined instrumental mass spectroscopy/NMR study reported elsewhere (S Pucci et al , manuscript in preparation). It was further defined using a comparison between a sample of 4 obtained by synthesis and a sample of 4 isolated by PLC or RP-PLC of the crude reaction product.

Remarkable α-regioselectivity in the rhodium-catalyzed hydroformylation of 2-vinylpyridine

Abstract The [{Rh(CO) 2 Cl} 2 ]/PPhMe 2 -catalyzed hydroformylation of 2-vinylpyridine gives the branched aldehyde 2-(2-pyridyl)propanal in good yield and 99% α-regioselectivity.

Ionspray tandem mass spectrometry for sensitive, rapid determination of minor toxic sesquiterpenoids in the presence of major analogues of the foreign green seaweed Caulerpa taxifolia which is invading the northwestern Mediterranean

A rapid and sensitive ionspray–ionization tandem MS method is presented for the determination of the toxic minor metabolites 10,11-epoxycaulerpenyne and caulerpenynol in the presence of the major metabolite, caulerpenyne, of the alien green seaweed Caulerpa taxifolia which is spreading in the northwestern Mediterranean. This method (a) showed no interference by any other metabolite or putative biogenetic intermediate of this seaweed, (b) needed HPLC injection merely in order to eliminate inorganic salts, (c) allowed determination of the three above compounds at the 50 µg l - 1 level no matter how large the excess of caulerpenyne, while being able to deal with the least amount of material compatible with handling, (d) revealed that also Indo-Pacific C. taxifolia contains all three key terpenoids above, albeit in lower amounts than the Mediterranean strain and (e) showed that none of these sesquiterpenoids was present at the above level of sensitivity in aquarium waters where the latter was growing.

Identification and characterization of Fenton oxidation products of surfactants by ionspray mass spectrometry and solid-phase microextraction gas chromatography mass spectrometry 1. Lauryl sulphate

The Fenton reaction for the degradation of surfactants has been investigated and partial degradation products have been identified and characterized by mass spectrometry for the case of lauryl sulphate. The polar soluble products were investigated by liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization (ESI), and the volatile products leaving the mixture during the reaction were trapped by means of solid-phase microextraction (SPME) and investigated by gas chromatography/mass spectrometry (GC/MS) with electron and chemical ionization. The oxidation leads to the formation of products with hydroxyl and epoxide groups due to insertion of oxygen atoms or to aldehydes derived from the loss of the hydrophilic sulphate group. The extent of mineralization is dependent on peroxide and iron concentrations. Copyright 1999 John Wiley & Sons, Ltd.

Identification of an Impurity in the Synthesis of Pharmacologically Active Pyrazolotriazolopyrimidines by a Combined Spectrometric Approach

Pyrazolotriazolopyrimidines are synthetic organic compounds showing interesting pharmacological activity. Good structural characterization and reliable evaluation of possible impurities is very important. We report here a detailed mass spectrometric investigation using different ionization techniques such as electron ionization, fast atom bombardment and Ionspray (IS). The approach allowed a reliable identification of an impurity, present in some of the derivatives examined, having a molecular weight 28 Da higher than the expected compound. It was identified as an ethyl derivative due to an unusual alkylating activity of ethyl orthoformate. The position of the ethyl group on the pyrazolotriazolopyrimidine ring was determined by 1H NMR. Finally, the use of IS combined with tandem mass spectrometry allowed a complete structural characterization of the target compounds as well as of the impurity.