ChemInform Abstract: Diversity-Oriented Synthesis of Furo[3,2-f]chromanes with Antimycobacterial Activity
Institut Pasteur, URA 2128 CNRS-Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris Cedex 15, France. European Journal of Medicinal Chemistry
(Impact Factor: 3.45).
02/2009; 44(6):2497-505. DOI: 10.1016/j.ejmech.2009.01.017
We previously reported the synthesis and the antimycobacterial activity of 4-(7,7-dimethyl-7H-furo[3,2-f]chromen-2-yl)pyridine. From this result, we sought to design simple synthetic accesses to related structures allowing the preparation of a diverse set of analogues. Two approaches were investigated. From 3-(2-bromo-7,7-dimethyl-8,9-dihydro-7H-furo[3,2-f]chromen-1-yl)propyl acetate, we prepared 2-arylated derivatives via Suzuki-Miyaura reactions between this bromine-bearing compound and various arylboronates. Moreover, and even more simple, we prepared the ((6-hydroxy-2,2,7,8-tetramethylchroman-5-yl)methyl)triphenylphosphonium salt via a selective bromination of 2,2,5,7,8-pentamethylchroman-6-ol. From this salt, a two stage Wittig reaction with an array of activated acids allowed the quick preparation of many analogues. The biological evaluation of the effect of these compounds on the growth of Mycobacterium bovis as well as Mycobacterium tuberculosis pointed out a fourfold improvement of the antimycobacterial properties for one of the compounds made. However, the many analogues which inhibited the growth of M. tuberculosis in the 0.6-5 microg/mL range turned out to be also cytotoxic on VERO cells growth at the same concentration range.
Available from: Maria De Rosa
- "In an effort to develop new anti-TB entities, Alvey et al. investigated a Wittig-type cyclization to prepare benzofurans (47). Using microwave irradiation, the reaction times could be shortened from 88 h to 1 h, compared with traditional reflux conditions. "
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ABSTRACT: Abstract Tuberculosis (TB) represents a major public health problem. The growing number of (extensively) multi-drug resistance cases indicates that there is an urgent need for discovery of new anti-TB entities, addressed towards new and specific targets, and continuous development of fast and efficient synthetic strategies to access them easily. Microwave-assisted chemistry is well suited for small-scale laboratory synthetic work, allowing full control of reaction conditions, such as temperature, pressure, and time. Microwave-assisted high-speed organic synthesis is especially useful in the lead optimization phase of drug discovery. To illustrate the advantages of modern microwave heating technology, we herein describe applications and approaches that have been useful for the synthesis of new drug-like anti-TB compounds.
Available from: Nick Terrett
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