6733-82-0Relevant academic research and scientific papers
A Minimalist Approach to the Design of Complexity-Enriched Bioactive Small Molecules: Discovery of Phenanthrenoid Mimics as Antiproliferative Agents
Alonso, Fernando,Quezada, María Josefina,Gola, Gabriel F.,Richmond, Victoria,Cabrera, Gabriela M.,Barquero, Andrea A.,Ramírez, Javier A.
supporting information, p. 1732 - 1740 (2018/08/01)
Over the last decades, much effort has been devoted to the design of the “ideal” library for screening, the most promising strategies being those which draw inspiration from biogenic compounds, as the aim is to add biological relevance to such libraries. On the other hand, there is a growing understanding of the role that molecular complexity plays in the discovery of new bioactive small molecules. Nevertheless, the introduction of molecular complexity must be balanced with synthetic accessibility. In this work, we show that both concepts can be efficiently merged—in a minimalist way—by using very simple guidelines during the design process along with the application of multicomponent reactions as key steps in the synthetic process. Natural phenanthrenoids, a class of plant aromatic metabolites, served as inspiration for the synthesis of a library in which complexity-enhancing features were introduced in few steps using multicomponent reactions. These resulting chemical entities were not only more complex than the parent natural products, but also interrogated an alternative region of the chemical space, which led to an outstanding hit rate in an antiproliferative assay: four out of twenty-six compounds showed in vitro activity, one of them being more potent than the clinically useful drug 5-fluorouracil.
Synthese stereoselective de 12α-amino et 12α-aminomethyl 19-nor-steroides
Doussot, Joel,Garreau, Robert,Dallery, Laurence,Guette, Jean-Paul,Guy, Alain
, p. 59 - 66 (2007/10/02)
Stereoselective synthesis of 12α-amino and 12α-aminomethyl 19-nor-steroids.The regio- and stereoselective introduction of an azido or a cyano group in the 12α-position of aromatic steroids was achieved by oxidative nucleophilic substitution (SNOx).A combination of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as an oxidant and cyano(trimethyl)silane (TMSCN) or azido(trimethyl)silane (TMSA) as a nucleophile thus led to the smooth functionalization of the 12α-position with high yields and selectivity.The method involves a two-step procedure : Δ 9-11 formation by dehydrogenation with DDQ/MeOH followed by oxidative nucleophilic substitution with DDQ in the presence of TMSA or TMSCN/LiClO4.During the second step, the carbocation generated in the medium is selectively attacked on the α face and leads to the more thermodynamically stable 12α-compounds, which were readily converted into the corresponding amino estrogens upon treatment with a variety of reducing reagents. Key words: regioselectivity / stereoselectivity / steroids / 2,3-dichloro-5,6-dicyanobenzoquinone
