The development of an enantioselective methodology for the total synthesis of the ansamycin antibiotics rifamycin S and streptovaricin D, and the hygrolide antibiotics bafilomycin A1 and elaiophylin is the long term goal of this proposal. These polypropionate natural products exhibit a broad range of biological activity. In recent years a great interest in their study and utilization (and that of some semisynthetic derivatives) as therapeutic agents has been evidenced by the extensive scientific literature being generated in this area. More specifically, we are proposing a formal total synthesis of rifamycin S, and the elaboration of the polypropionate units of streptovaricin D, bafilomycin A1 and elaiophylin, based on the utilization of oxirane chemistry. The selection of these target molecules is based on their notable biological activity, the great interest in their synthesis shown by other research groups, and the challenge that represents the elaboration of the different configurations found in their polypropionate units by the same methodology. The reported synthetic approaches to these targets, as for many other polypropionate systems, have been usually based on aldol and related chemistry. We believed that the utilization of epoxide chemistry as a general approach to these systems will be well received by the synthetic community. Our approach is a reiterative one and is based on the stereoselective epoxidation of homoallylic alcohols by means of iodocylisation reactions followed their cleavage via organoaluminium chemistry. With this methodology we can control the configuration of the methyl and hydroxyl groups which characterize the polypropionate units. Not only the desired chemical transformations proposed in this extensive study will be accomplished. The scope, limitations, stereochemistry and mechanistic implications of the key reactions included in this study will be examined. Although our methodology will be applied to these specific targets in principle its should be applicable to many other polypropionate systems.
| Ramírez-Camejo, Luis A; Maldonado-Morales, Génesis; Bayman, Paul (2017) Differential Microbial Diversity in Drosophila melanogaster: Are Fruit Flies Potential Vectors of Opportunistic Pathogens? Int J Microbiol 2017:8526385 |
| Morales-Rivera, Keyla F; Piñero Cruz, Dalice M; Prieto, Jose A (2017) Crystal structure of (-)-(S)-4-[(2S,3S,4S,Z)-3-hydroxy-4-methyl-hept-5-en-2-yl]-1,3-dioxolan-2-one. Acta Crystallogr E Crystallogr Commun 73:1070-1072 |
| García-Arriaga, Marilyn; Acosta-Santiago, Maxier; Cruz, Antony et al. (2017) Probing the Limits of Supramolecular G-Quadruplexes Using Atomistic Molecular Dynamics Simulations. Inorganica Chim Acta 468:209-222 |
| Huang, Qing; Quiñones, Edwin (2016) A spectroscopic method to determine the activity of the restriction endonuclease EcoRV that involves a single reaction. Anal Biochem 497:103-5 |
| Mège, Pascal; Schizas, Nikolaos V; Reyes, Joselyd García et al. (2015) Genetic seascape of the threatened Caribbean elkhorn coral, Acropora palmata, on the Puerto Rico Shelf. Mar Ecol (Berl) 36:195-209 |
| Morales-Rivera, Amarilys; Hernández-Burgos, Mayté M; Martínez-Rivera, Arlene et al. (2014) Anxiolytic effects of oxytocin in cue-induced cocaine seeking behavior in rats. Psychopharmacology (Berl) 231:4145-55 |
| Ramírez-Camejo, Luis A; Torres-Ocampo, Ana P; Agosto-Rivera, José L et al. (2014) An opportunistic human pathogen on the fly: strains of Aspergillus flavus vary in virulence in Drosophila melanogaster. Med Mycol 52:211-9 |
| Martínez-Rivera, Arlene; Rodríguez-Borrero, Enrique; Matías-Alemán, María et al. (2013) Metabotropic glutamate receptor 5 within nucleus accumbens shell modulates environment-elicited cocaine conditioning expression. Pharmacol Biochem Behav 110:154-60 |
| Galindo-Cardona, Alberto; Acevedo-Gonzalez, Jenny P; Rivera-Marchand, Bert et al. (2013) Genetic structure of the gentle Africanized honey bee population (gAHB) in Puerto Rico. BMC Genet 14:65 |
| Santiago-Rodriguez, Tasha M; Rivera, Jessica I; Coradin, Mariel et al. (2013) Antibiotic-resistance and virulence genes in Enterococcus isolated from tropical recreational waters. J Water Health 11:387-96 |
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