116569-09-6Relevant articles and documents
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Hartmann,Panizzon
, p. 1327,1330 (1936)
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Method for preparing indole-2,3-dione derivatives by catalytic oxidation of microwave copper/peroxyacetic acid
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Paragraph 0024; 0050, (2018/09/08)
The invention discloses a method for preparing indole-2,3-dione derivatives by catalytic oxidation of microwave copper/peroxyacetic acid. The method comprises the following steps: a catalytic amount of catalyst copper iodide, indole, a derivative of the indole and peroxyacetic acid are added into a reaction vessel, wherein the indole, the derivative of the indole and the peroxyacetic acid are usedas raw materials, ethanol is used as a solvent, the reaction vessel is placed into a microwave reaction instrument, a reaction is performed at certain temperature and power, after a certain time, reduced-pressure concentration is performed, and a product is purified by column chromatography. The method provided by the invention is a method having novel raw materials, simple operation and high efficiency used for preparing a benzimidazole derivative; and compared with the prior art, the method provided by the invention has an obviously-accelerated reaction speed than that under conventional heating, mild reaction conditions, simple operation, a high yield, safety, low costs and environmental protection.
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.
DERIVATIVES OF UNCIALAMYCIN, METHODS OF SYNTHESIS AND THEIR USE AS ANTITUMOR AGENTS
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Page/Page column 75; 76, (2015/02/25)
In one aspect, the present disclosure provides new analogs of uncialamycin of formulae (I) and (II). The present disclosure also provides novel synthetic pathways to obtaining uncialamycin and analogs thereof. Additionally, the present disclosure also describes methods of use of uncialamycin and analogs thereof. In another aspect, the present disclosure provides antibody-drug conjugates comprising the compounds of formulae (I) and (ll).