517920-59-1Relevant articles and documents
Stereoselective gem-C,B-Glycosylation via 1,2-Boronate Migration
He, Zhi-Tao,Li, Rui-Peng,Liao, Qi-Ying,Ma, Chao,Wang, Miao,Zhao, Wei-Cheng
supporting information, p. 2460 - 2467 (2022/02/16)
A novel protocol is established for the long-standing challenge of stereoselective geminal bisglycosylations of saccharides. The merger of PPh3 as a traceless glycosidic leaving group and 1,2-boronate migration enables the simultaneous introduction of C-C and C-B bonds at the anomeric stereogenic center of furanoses and pyranoses. The power of this method is showcased by a set of site-selective modifications of glycosylation products for the construction of bioactive conjugates and skeletons. A scarce metal-free 1,1-difunctionalization process of alkenes is also concomitantly demonstrated.
(o-Phenylenediamino)borylstannanes: Efficient Reagents for Borylation of Various Alkyl Radical Precursors
Suzuki, Kensuke,Nishimoto, Yoshihiro,Yasuda, Makoto
supporting information, p. 3968 - 3973 (2020/12/30)
(o-Phenylenediamino)borylstannanes were newly synthesized to achieve radical boryl substitutions of a variety of alkyl radical precursors. Dehalogenative, deaminative, decharcogenative, and decarboxylative borylations proceeded in the presence of a radica
Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7 (β5i)
Klein, Markus,Busch, Michael,Friese-Hamim, Manja,Crosignani, Stefano,Fuchss, Thomas,Musil, Djordje,Rohdich, Felix,Sanderson, Michael P.,Seenisamy, Jeyaprakashnarayanan,Walter-Bausch, Gina,Zanelli, Ugo,Hewitt, Philip,Esdar, Christina,Schadt, Oliver
, p. 10230 - 10245 (2021/07/26)
Proteasomes are broadly expressed key components of the ubiquitin-dependent protein degradation pathway containing catalytically active subunits (β1, β2, and β5). LMP7 (β5i) is a subunit of the immunoproteasome, an inducible isoform that is predominantly expressed in hematopoietic cells. Clinically effective pan-proteasome inhibitors for the treatment of multiple myeloma (MM) nonselectively target LMP7 and other subunits of the constitutive proteasome and immunoproteasome with comparable potency, which can limit the therapeutic applicability of these drugs. Here, we describe the discovery and structure-based hit optimization of novel amido boronic acids, which selectively inhibit LMP7 while sparing all other subunits. The exploitation of structural differences between the proteasome subunits culminated in the identification of the highly potent, exquisitely selective, and orally available LMP7 inhibitor 50 (M3258). Based on the strong antitumor activity observed with M3258 in MM models and a favorable preclinical data package, a phase I clinical trial was initiated in relapsed/refractory MM patients.