56263-51-5Relevant articles and documents
Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations
Nicolaou,Wang, Yanping,Lu, Min,Mandal, Debashis,Pattanayak, Manas R.,Yu, Ruocheng,Shah, Akshay A.,Chen, Jason S.,Zhang, Hongjun,Crawford, James J.,Pasunoori, Laxman,Poudel, Yam B.,Chowdari, Naidu S.,Pan, Chin,Nazeer, Ayesha,Gangwar, Sanjeev,Vite, Gregory,Pitsinos, Emmanuel N.
supporting information, p. 8235 - 8246 (2016/07/15)
From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy.
Molecular Tweezers from Cyclophane Building Blocks
Guether, Ralf,Nieger, Martin,Rissanen, Kari,Voegtle, Fritz
, p. 743 - 758 (2007/10/02)
Molecular tweezer compounds 1-6 with convergent carboxyl groups are prepared from suitable functionalized - and dithiametacyclophane building blocks by using several multistep strategies.The C-C coupling of two cyclophanes according to the Hagih
Macrocyclic polyether carboxylic acids
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, (2008/06/13)
A series of novel, macrocyclic polyether compounds. The macrocycles have a 21-membered ring, containing six oxygen atoms, and they have a carboxy group (or a salt thereof) directed towards the interior of the ring. Administration of the compounds of the invention to ruminant animals (e.g. cattle and sheep) modifies their digestive fermentation processes such that the volatile fatty acids produced in the rumen contain a higher proportion of propionates rather than acetates, thereby increasing the efficiency of feed utilization in said ruminant animals. Additionally, the compounds of the invention show antibacterial activity in vitro against certain gram-positive microorganisms.