1.Crystal structures of two 6-(2-hy-droxy-benzo-yl)-5H-thia-zolo[3,2-a]pyrimidin-5-ones.
Gomes LR1, Low JN2, Cagide F3, Borges F3. Acta Crystallogr E Crystallogr Commun. 2015 Jun 13;71(Pt 7):766-71. doi: 10.1107/S2056989015011044. eCollection 2015.
The title compounds, 6-(2-hy-droxy-benz-yl)-5H-thia-zolo[3,2-a]pyrimidin-5-one, C13H8N2O3S, (1), and 6-(2-hy-droxy-benz-yl)-3-methyl-5H-thia-zolo[3,2-a]pyrimidin-5-one, C14H10N2O3S, (2), were synthesized when a chromone-3-carb-oxy-lic acid, activated with (benzotriazol-1-yl-oxy)tripyrrolidinyl-phospho-nium hexa-fluorido-phosphate (PyBOP), was reacted with a primary heteromamine. Instead of the expected amidation, the unusual title thia-zolo-pyrimidine-5-one derivatives were obtained serendipitously and a mechanism of formation is proposed. Both compounds present an intra-molecular O-H⋯O hydrogen bond, which generates an S(6) ring. The dihedral angles between the heterocyclic moiety and the 2-hydroxybenzoyl ring are 55.22 (5) and 46.83 (6)° for (1) and (2), respectively. In the crystals, the mol-ecules are linked by weak C-H⋯O hydrogen bonds and π-π stacking inter-actions.
2.[Unusual amidation reaction of Asn-containing glycopeptide antibiotics using the coupling reagent PyBOP].
Olsuf'eva EN, Solov'eva SE, Reznikova MI, Korolev AM, Preobrazhenskaia MN. Bioorg Khim. 2013 Mar-Apr;39(2):141-50.
The coupling reagent PyBOP is widely used for the synthesis of different peptides and their amides, particularly for carboxamides of glycopeptide antibiotics of vancomycin or teicoplanin groups. The amidation reaction of the peptide core of the glycopeptide antibiotic eremomycin (I) with highly reactive amines in the presence of PyBOP is usually not accompanied by the formation of side products. However, the amidation of I with bulky amines (e.g., decyl amine and adamantyl amine) in the presence of PyBOP and Et3N or di-(i-Pr)2EtN (pH - 8.5) yielded N-unsubstituted carboxamide of eremomycin (Ia) as an admixture. The reaction of (I) or vancomycin (II) with an excess of PyBOP and Et3N (pH - 8.5) without addition of an amine or ammonia gave a mixture of products which contained higher amounts of the corresponding N-unsubstituted carboxamides (-20%). The structures of the samples of Ia and vancomycin amide (IIa) were proved by 1H NMR and ESI MS methods and confirmed by comparing with the authentic samples.
4.Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors.
Biava M1, Battilocchio C2, Poce G2, Alfonso S2, Consalvi S2, Di Capua A3, Calderone V4, Martelli A4, Testai L4, Sautebin L5, Rossi A5, Ghelardini C6, Di Cesare Mannelli L6, Giordani A7, Persiani S7, Colovic M7, Dovizio M8, Patrignani P8, Anzini M3. Bioorg Med Chem. 2014 Jan 15;22(2):772-86. doi: 10.1016/j.bmc.2013.12.008. Epub 2013 Dec 18.
We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema.