{"id":2587,"date":"2020-02-12T13:50:15","date_gmt":"2020-02-12T17:50:15","guid":{"rendered":"https:\/\/sintmol.ufms.br\/?page_id=2587"},"modified":"2026-05-12T09:29:11","modified_gmt":"2026-05-12T13:29:11","slug":"umbrella-project-iv-diversity-oriented-synthesis-dos","status":"publish","type":"page","link":"https:\/\/sintmol.ufms.br\/en\/research-and-development\/umbrella-project-iv-diversity-oriented-synthesis-dos\/","title":{"rendered":"Umbrella Project IV"},"content":{"rendered":"

Diversity-Oriented Synthesis (DOS)<\/h3>\n

Althou\"\"<\/a>gh rational planning is widely used in the development of new drugs by research groups, both in industry and academia, it is not the only work strategy. Identifying small molecules that have biological and medical applications does not always require knowledge about the macromolecule on which the compound will act. The biological evaluation of compounds in cells and even in microorganisms can also be of great value and enlightening. However, in order to achieve good results in evaluating the potential of these small molecules, it is necessary that they be part of a quite diverse collection regarding their structural variations. Compound libraries designed using combinatorial chemistry (target-oriented synthesis) are rarely effective when the structure of the target protein is unknown, and this is due to the low diversity found in these libraries [1, 2]. Recently, some research groups have explored novel approaches based on modifying a given structure to generate molecular diversity with spectacular results [3-6]. Given the novelty of this strategy, in this project we are interested in discovering new antimicrobial agents (antibacterial, antifungal, antivirus) by screening small molecules with high structural diversity based on the Diels-Alder adduct tricyclo [6.2.1.02,7<\/sup>]-undeca-4,9-diene-3,6-dione (1<\/strong>), obtained from the reaction between cyclopentadiene and para<\/em>-benzoquinone. In order to obtain a library of these molecules, we are proposing to use diversity-oriented synthesis (DOS) as a strategy [2]. The proposal seeks to synthesize at least nine distinct molecular skeletons from this raw material, which corresponds to the reagent-based approach (i.e., common starting material and different reagents). Therefore, several reagents will be used to promote 1,3-dipolar cycloadditions, additions, reductions and cyclizations, molecular rearrangements, ring expansions, etc. From these different molecular skeletons, it will be possible to attain a hundred new organic compounds with four types of molecular diversity incorporated into their structures: i) diversity of substituents; ii) diversity of functional groups; iii) stereochemical diversity; and iv) diversity of molecular skeletons.<\/p>\n

References:<\/strong><\/p>\n[1] Sangi, D. P. Quim. Nova<\/em> 2016<\/strong>, 39<\/em>, 995<\/a>.<\/p>\n[2] Schreiber, S. L. Science<\/em> 2000<\/strong>, 287<\/em>, 1964.<\/a> <\/p>\n[3] Llabani, E.; Hicklin, R. W.; Lee, H. Y. et al. Nature Chem.<\/em> 2019<\/strong>, 11, 521<\/a>.<\/p>\n[4] Kato, N.; Comer, E.; Sakata-Kato, T. et al. <\/i> Nature<\/i> 2016<\/strong>, 538,<\/em>344.<\/a> <\/p>\n[5] Morrison, K. C.; Hergenrother, P. J.   Nat. Prod. Rep.<\/strong><\/i> 2014<\/strong>, 31<\/em>, 6<\/a>.<\/p>\n[6] Huigens III, R. W.; Morrison, K. C.; Hicklin, R. et al.<\/i>  Nature Chem. <\/i>2013<\/strong>,<\/i> 5<\/em>, <\/b>195.<\/a><\/p>\n

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Selected Publications<\/strong><\/p>\n