José M. Llera

An efficient synthesis of both enantiomers of chiral non racemic methylsulfoxides from DAG

Abstract Diacetone-D-Glucose is stereoselectively converted to its (S)- or (R)-methanesulfinates 1 and 2 in 90 and 87% yield by treatment with methylsulfinyl chloride in the presence of diisopropylethylamine or pyridine, respectively. After purification, sulfinates 1 and 2 were transformed into both epimers of enantiomerically pure methylsulfoxides by reaction with Grignard reagents.

Physical characterization of carteolol: Eudragit® L binding interaction

Eudragit® L 30D was used as a carrier to prepare carteolol polymeric complexes in order to obtain controlled release dosage forms. The polyanionic form of the polymer, neutralized at different degrees, reacts readily with carteolol hydrochloride to give water-insoluble complexes. Carteolol complexes were characterized by differential scanning calorimetry, IR, 1H- and 13C-NMR spectroscopy. In fact, results indicated that there were intermolecular associations between the polymer and the drug consisting in ammonium salt interactions. Maximum carteolol content was found to be 22% in the complexes.

Morphine polymeric coprecipitates for controlled release : elaboration and characterization

Coprecipitates of morphine were prepared by using EudragitR L30D as a carrier in order to obtain controlled release dosage systems. Differential Scanning Calorimetry and IR, 1H- and 13C-NMR spectroscopies were applied in order to explain the mechanism of this interaction. The results obtained indicated that there was an intermolecular association between the polymer and the drug consisting in two different hydrogen bonds interactions. The proposed reaction involves coprecipitates having morphine contents greater than 50%.

Study of a complexation process between naltrexone and Eudragit® L as an oral controlled release system

Abstract Polymeric complexes based on the interaction between Eudragit® L and naltrexone hydrochloride were elaborated. A preformulation study of the drug was designed to address the following points: (a) the development of two alternative methods (high performance liquid chromatography (HPLC) and UV spectrophotometry) for the analysis and quantifying of naltrexone; (b) the determination of the aqueous solubility of naltrexone hydrochloride; and (c) the characterization of naltrexone hydrochloride from the following points of view: morphological (scanning electronic microscopy, SEM), thermal (differential scanning calorimetry, DSC and hot stage-microscopy, HSM) and spectroscopical (1H- and 13C-nuclear magnetic resonance, NMR). Furthemore, some of these thechniques were used for the physical and chemical characterization of naltrexone polymeric complexes. An interaction by means of hydrogen bonds between the polymer and naltrexone was demonstrated using NMR spectroscopic techniques. The in vitro release of naltrexone-Eudragit® L complex using a pH gradient technique was studied. A significant reduction in the release rate of drug from the complex used as naltrexone controlled release system as well as a very high efficiency in the dissolution process have been found.

Palladium-Catalyzed Allylic Nucleophilic Substitution Reactions of (E)-γ-Acetoxy-α,β-unsaturated p-Tolylsulfoxides.

Abstract Regio- and diastereoselective nucleophilic allylic substitutions of optically pure (E)-γ-acetoxy-α,β-unsaturated p-tolylsulfoxides 2 and 3 with sodium dimethyl malonate have been carried out. The reactivity of these substrates is controlled by both the chiral sulfinyl group and the size of the alkyl group attached at the γ-terminus of the allylic system. This process constitutes an example of palladium-mediated resolution of a 1:1 mixture of acetates 2 and 3.

Efficient preparation of enantiomerically pure (E)-γ-hydroxy-α,β-unsaturated p-tolylsulfoxides using lipase-mediated acylations

Abstract ( E )-γ-Hydroxy-α,β-unsaturated p -tolylsulfoxides 1 have been efficiently resolved via irreversible enzymatic acylation with lipase PS ( Pseudonomas cepacia ) and vinyl acetate.

Asymmetric synthesis of both diastereomers of protected S-methyl-l-cysteine and S-n-propyl-l-cysteine sulphoxides

Abstract The preparation of both isomers at sulphur of N -(benzyloxycarbonyl)- S -methyl (-propyl)- S -oxo- l -cysteine methyl ester has been carried out using l -cysteine and diacetone- d -glucose (DAG) as starting material and inductor of the chirality at sulphur, respectively.

STEREOCHEMISTRY OF SULPHUR ORGANIC COMPOUNDS. PART 23. DOUBLE GAUCHE EFFECT OXYGEN/SULPHUR IN 2-ALKYLTHIO-DERIVAHVES OF 1,1-DIMETHOXYETHANE

Abstract The synthesis and conformational analysis, by 1H-NMR in several solvents, of 2-X-1,1-dimethoxyethane (X: MeS, EtS, tPrS, tBuS, BnS, SOMe, SOEt, SOiPr, SOiBu, SOBn) are reported. The results are concordant with a high, unexpected, solvent independent preference (∼30%) of the sterically most hindered conformation. A stereoelectronic interaction between orbitals has been invoked to explain the obtained results. MM2 method was used to calculate the energy of the conformations resulting from CH[sbnd]CH2 bond rotation.

Stereochemistry of sulphur organic compounds. Part 24. Synthesis and conformational analysis of cis- and trans-2-methoxy-5-methylthio derivatives of oxane

The synthesis and conformational analysis of cis- and trans-2-methoxy-5-X-oxane, by 13C n.m.r. at low temperature in several solvents, are reported. ΔG° Values in CD2Cl2 of trans-isomers are –0.61 (X, SMe), +1.65 (X, SOMe more polar isomer), +0.57 (X, SOMe less polar isomer), –0.50 (X, SO2Me), and +1.4 (X, +SMe2) kcal mol–1, negative values indicating a preference for the diequatorial conformer. In all cis-compounds only one conformation is present. By comparison of these values with those calculated from 2-methoxyoxane and 3-methylthio derivatives of oxane the role played by the anomeric effect on the (oxygen–sulphur)1,2-g interaction can be inferred.

Asymmetric Synthesis of Alkyl and Aryl Sulfinates of DAG: An Improved and General Route to Both Enantiomerically Pure Sulfoxides

Abstract A short, efficient and general route for the preparation of o.p. alkyl and aryl sulfinates is described. Both epimers at sulfur can be obtained using DAG as unique inductor of chirality and, only by choosing the adequate base (Py or i-Pr2NEt), the configuration at sulfur can be predicted. The efficiency of this methodology has been demonstrated by the synthesis of o.a. alkyl aryl and dialkyl sulfoxides with high e.e. (up to 100%).