52389-39-6Relevant articles and documents
Synthesis of Aryl C-Glycosides via Iron-Catalyzed Cross Coupling of Halosugars: Stereoselective Anomeric Arylation of Glycosyl Radicals
Adak, Laksmikanta,Kawamura, Shintaro,Toma, Gabriel,Takenaka, Toshio,Isozaki, Katsuhiro,Takaya, Hikaru,Orita, Akihiro,Li, Ho C.,Shing, Tony K. M.,Nakamura, Masaharu
supporting information, p. 10693 - 10701 (2017/08/15)
We have developed a novel diastereoselective iron-catalyzed cross-coupling reaction of various glycosyl halides with aryl metal reagents for the efficient synthesis of aryl C-glycosides, which are of significant pharmaceutical interest due to their biological activities and resistance toward metabolic degradation. A variety of aryl, heteroaryl, and vinyl metal reagents can be cross-coupled with glycosyl halides in high yields in the presence of a well-defined iron complex, composed of iron(II) chloride and a bulky bisphosphine ligand, TMS-SciOPP. The chemoselective nature of the reaction allows the use of synthetically versatile acetyl-protected glycosyl donors and the incorporation of various functional groups on the aryl moieties, producing a diverse array of aryl C-glycosides, including Canagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), and a prevailing diabetes drug. The cross-coupling reaction proceeds via generation and stereoselective trapping of glycosyl radical intermediates, representing a rare example of highly stereoselective carbon-carbon bond formation based on iron catalysis. Radical probe experiments using 3,4,6-tri-O-acetyl-2-O-allyl-α-d-glucopyranosyl bromide (8) and 6-bromo-1-hexene (10) confirm the generation and intermediacy of the corresponding glycosyl radicals. Density functional theory (DFT) calculations reveal that the observed anomeric diastereoselectivity is attributable to the relative stability of the conformers of glycosyl radical intermediates. The present cross-coupling reaction demonstrates the potential of iron-catalyzed stereo- and chemoselective carbon-carbon bond formation in the synthesis of bioactive compounds of certain structural complexity.
The reaction of penta-O-benzoyl-D-glucopyranose with piperidine: Characterization of the products isolated and study of the reaction mechanism
Salinas, Amelia E.
, p. 34 - 46 (2007/10/03)
The reaction of penta-O-benzoyl-D-glucopyranose with piperidine gave N-(2,3,6-tri-O-benzoyl-β-D-glucopyranosyl)piperidine (44.1%), N-(2,4,6-tri-O-benzoyl-β-D-glucopyranosyl)piperidine (1.5%), N-benzoylpiperidine and piperidinium benzoate (approx 1 mol of each of these two products per mol of substrate). When several penta-O-benzoyl-D-glucopyranoses containing selectively 14C-labeled benzoyloxy groups were submitted to the same reaction, it was found that N-benzoylpiperidine is formed at the expense of benzoyloxy-C-1, piperidinium benzoate arises mainly from benzoyloxy-C-2, and the benzoyloxy groups originally attached to C-3, C-4, and C-6 remain in the major product of the reaction. These results demonstrate that the first compound produced in the reaction is N-(3,4,6-tri-O-benzoyl-β-D-glucopyranosyl)piperidine, which could not be isolated because it undergoes two consecutive benzoyl migrations: a migration from O-3 to O-2 to give the 2,4,6-tri-O-benzoate, followed by a migration from O-4 to O-3 to afford the 2,3,6-tri-O-benzoate. A mechanism to explain the formation of piperidinium benzoate from benzoyloxy-C-2 of penta-O-benzoyl-D-glucopyranose is proposed. Copyright (C) 1999 Elsevier Science Ltd.
