Intramolecular [3+2] Cycloaddition of Fused Azolo-Azepanes from Azido Monosaccharides Derivatives

CARBOHYDRATE SYMPOSIUM BIENNIAL MEETING OF THE CHEMICAL BIOLOGY GROUP 14th - 16th March 2016 Centro de Investigaciones Biológicas - CSIC www.madrid2016.cib.csic.es PC64. M. S. Pino-González Intramolecular [3+2] Cycloaddition of Fused Azolo-Azepanes from Azido Monosaccharide Derivatives M. Soledad Pino-González,a Antonio Romero-Carrasco,a Saturnino Calvo-Losada,b J. Joaquín Quiranteb a) Departamento de Química Orgánica; b) Departamento de Química Física. Facultad de Ciencias. Campus de Teatinos, s/n. Universidad de Málaga. 29071 Málaga,Spain; e-mail: [email protected] Bicyclic aromatic compounds have shown an enhanced potency as inhibitors and therefore a number of tetrazoles, triazoles and imidazoles, fused to pyranoses and furanoses have been synthesized.[1] The glucotetrazole 2 was designed as a bicyclic neutral transition state analogue inhibitor of b-glucosidases and glycogen phosphorylase. The mannose analogue 3 is an inhibitor of mannosidases and the glucotriazole 4 is a competitive inhibitor of glycogen phosphorylase. In previous experiences, we have synthesized polyhydroxyazepane derivatives with amide, aminomethyl or hydroxymethyl groups, starting from epoxyamides.[2] Now, with the aim of obtaining new inhibitors, we are interested in the formation of bicyclic compounds with azepanes fused to azoles (5,6,7). Azoles are profusely found in bioactive products but few tetrazoles[3] and triazoles fused to polyhydroxyazepanes have been reported to be evaluated as inhibitors. The methodology carried out to form the heterocyclic ring is based on intramolecular [3+2] cycloaddition of azido monosaccharide derivatives containing ciano or other unsaturated groups. In order to elucidate the mechanism of formation of the bicyclic products, a quantum chemical topological study has been carried out. Acknowledgements: to Ministerio de Economía y Competitividad (MINECO) (CTQ2014-60223-R) and to Junta de Andalucía (FQM-158) for financial support. References [1] Tailford, L. E.; Offen, W.; Smith, N. L.; Dumon, C.; Morland, C.; Gratien, J.; Heck, M-P.; Stick, R. V.; Blériot, Y.; Vasella, A.; Gilbert, H. J; Davies, G. J. Nat. Chem. Biol. 2008, 4, 306. [2] Oña, N.; Romero-Carrasco, A.; Pino-González, M. S. Tetrahedron: Asymmetry 2013, 24, 156 and references therein. [3] Paz, N. R.; Santana, A. G.; Francisco, C. G.; Suárez, E.; González, C. C. Org. Lett. 2012, 14, 3388. Mascareñas Cid, Jose Luis CIQUS-University of Santiago de Compostela, Spain. Committee Matheu Malpartida, Maribel University Rovira i Virgili of Tarragona. Spain. Delegate Mayan, María D. INIBIC-SERGAS. A Coruña, Spain. OC09 Mazo, Nuria University of La Rioja. Logroño, Spain. FC05 Mendoza, Fernanda University Autonomous of Barcelona. Spain. PC65 Merino, Pedro University of Zaragoza. Spain. IL12 Miguel Ávila, Joan CIQUS-University of Santiago de Compostela, Spain. Delegate Millet, Óscar CIC bioGUNE. Derio, Spain. PC42 Miranda, Silvia IQOG-CSIC. Madrid, Spain. PC67 Montalvillo, Laura IQOG-CSIC. Madrid, Spain. PC23 Montenegro, Javier CIQUS-University of Santiago de Compostela. Spain. OC02 Montes, Helena University of Burgos. Spain. FC19 Moraleda, Jose Luis Rovi Sponsor Morales, Juan Carlos IPB-CSIC. Granada, Spain. PC63 Nieto, Manuel CIB, CSIC. Madrid, Spain. FC02 Nieto, Pedro IIQ-CSIC. Sevilla, Spain. PC20 Ortega Muñoz, Mariano University of Granada. Spain. Delegate Ortega, Laura CIB-CSIC. Madrid, Spain. PC07 Ortega-Gutiérrez, Silvia University Complutense of Madrid. Spain. OC05 Ortiz Mellet, Carmen University of Sevilla. Spain. PC33 Pablos Lagartos, Jesús Luis ICTP-CSIC. Madrid, Spain. PC16 Pacheco, Pedro Jose University of Castilla-La Mancha. Albacete, Spain. PC01 Pando, Daniel Nanovex Sponsor Pedroso, Enrique University of Barcelona. Spain. Delegate Pellegrino, Teresa Italian Institute of Technology. Genova, Italy. IL06 Peñalver, Pablo IPB-CSIC. Granada, Spain. FC14 Peregrina García, Manuel Jesús University of La Rioja. Logroño, Spain. Committee Pérez-Ojeda, María Eugenia IQFR-CSIC. Madrid, Spain. OC08 Pérez-Regidor, Lucía CIB-CSIC. Madrid, Spain. PC66, Committee Pérez-Sala, Dolores CIB-CSIC. Madrid, Spain. IL03 Pingarrón, Jose Manuel University Complutense of Madrid. Spain. IL01 Pino-González, Mª Soledad University of Málaga. Spain. PC64 Piquero, Marta University Complutense of Madrid. Spain. PC27 Planas, Antoni IQS-University Ramon Lull. Barcelona, Spain. PL4 Planas, Antoni IQS-University Ramon Llull. Barcelona, Spain. PC30 Plou, Francisco ICP-CSIC. Madrid, Spain. PC15, Committee Prado, Verónica CIQUS-University of Santiago de Compostela, Spain. FC09 Priegue, Juan Manuel CIQUS-University of Santiago de Compostela, Spain. PC13 Quesada, Roberto University of Burgos. Spain. PC29 Ramírez-Escudero, Mercedes IQFR-CSIC. Madrid, Spain. FC17 Rauter, Amélia P. University of Lisboa. Portugal. IL14 Reichardt, Niels-Christian CIC bioGUNE. Derio, Spain. Delegate Roca, María Teresa University of Castellón. Spain. OC01 Rodriguez, Diana CIQUS-University of Santiago de Compostela, Spain. PC44