23617-71-2Relevant 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.
Isosteric analogs of lenalidomide and pomalidomide: Synthesis and biological activity
Ruchelman, Alexander L.,Man, Hon-Wah,Zhang, Weihong,Chen, Roger,Capone, Lori,Kang, Jian,Parton, Anastasia,Corral, Laura,Schafer, Peter H.,Babusis, Darius,Moghaddam, Mehran F.,Tang, Yang,Shirley, Michael A.,Muller, George W.
, p. 360 - 365 (2013/02/23)
A series of analogs of the immunomodulary drugs lenalidomide (1) and pomalidomide (2), in which the amino group is replaced with various isosteres, was prepared and assayed for immunomodulatory activity and activity against cancer cell lines. The 4-methyl and 4-chloro analogs 4 and 15, respectively, displayed potent inhibition of tumor necrosis factor-α (TNF-α) in LPS-stimulated hPBMC, potent stimulation of IL-2 in a human T cell co-stimulation assay, and anti-proliferative activity against the Namalwa lymphoma cell line. Both of these analogs displayed oral bioavailability in rat.
Stable reagents for the generation of N-centered radicals: Hydroamination of norbornene
Kemper, Jens,Studer, Armido
, p. 4914 - 4917 (2007/10/03)
(Chemical Equation Presented) Radical transfer hydroaminations have been achieved with 3-aminated 1,4-cyclohexadienes rather than transition-metal reagents (see scheme; DTBP = di-tert-butylperoxide). These functionalized cyclohexadienes are efficient N-radical precursors. Moreover, they are stable and readily prepared, and radical generation occurs under neutral conditions.
