Synthetic Remodeling of the Chartreusin Pathway to Tune Antiproliferative and Antibacterial Activities was written by Ueberschaar, Nico;Xu, Zhongli;Scherlach, Kirstin;Metsae-Ketelae, Mikko;Bretschneider, Tom;Dahse, Hans-Martin;Goerls, Helmar;Hertweck, Christian. And the article was included in Journal of the American Chemical Society in 2013.Electric Literature of C8H7BrO3 This article mentions the following:
Natural products of the benzonaphthopyranone class, such as chartreusin, elsamicin A, gilvocarcin, and polycarcin, represent potent leads for urgently needed anticancer therapeutics and antibiotics. Since synthetic protocols for altering their architectures are limited, we harnessed enzymic promiscuity to generate a focused library of chartreusin derivatives Pathway engineering of the chartreusin polyketide synthase, mutational synthesis, and mol. modeling were employed to successfully tailor the structure of chartreusin. For the synthesis of the aglycons, improved synthetic avenues to substituted coumarin building blocks were established. Using an engineered mutant, in total 11 new chartreusin analogs (desmethyl, Me, Et, vinyl, ethynyl, bromo, hydroxy, methoxy, and corresponding (1→2) abeo-chartreusins) were generated and fully characterized. Their biol. evaluation revealed an unexpected impact of the ring substituents on antiproliferative and antibacterial activities. Irradiation of vinyl- and ethynyl-substituted derivatives with blue light resulted in an improved antiproliferative potency against a colorectal cancer cell line. In contrast, the replacement of a Me group by hydrogen caused a drastically decreased cytotoxicity but markedly enhanced antimycobacterial activity. Furthermore, muta-synthesis of bromochartreusin led to the first crystal structure of a chartreusin derivative that is not modified in the glycoside residue. Beyond showcasing the possibility of converting diverse, fully synthetic polyphenolic aglycons into the corresponding glycosides in a whole-cell approach, this work identified new chartreusins with fine-tuned properties as promising candidates for further development as therapeutics. In the experiment, the researchers used many compounds, for example, Methyl 3-bromo-5-hydroxybenzoate (cas: 192810-12-1Electric Literature of C8H7BrO3).
Methyl 3-bromo-5-hydroxybenzoate (cas: 192810-12-1) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. Commercially available organobromine pharmaceuticals include the vasodilator nicergoline, the sedative brotizolam, the anticancer agent pipobroman, and the antiseptic merbromin. Electric Literature of C8H7BrO3
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary