364-12-5Relevant articles and documents
Single C?F Bond Cleavage of Trifluoromethylarenes with an ortho-Silyl Group
Yoshida, Suguru,Shimomori, Ken,Kim, Youngchan,Hosoya, Takamitsu
supporting information, p. 10406 - 10409 (2016/08/24)
The transformation of a single C?F bond of trifluoromethylarenes bearing a hydrosilyl group at the ortho position was achieved. The activation of the hydrosilyl group with a trityl cation in the presence of nucleophiles allowed for selective C?F bond func
Identification and development of biphenyl substituted iminosugars as improved dual glucosylceramide synthase/neutral glucosylceramidase inhibitors
Ghisaidoobe, Amar T.,Van Den Berg, Richard J. B. H. N.,Butt, Saleem S.,Strijland, Anneke,Donker-Koopman, Wilma E.,Scheij, Saskia,Van Den Nieuwendijk, Adrianus M. C. H.,Koomen, Gerrit-Jan,Van Loevezijn, Arnold,Leemhuis, Mark,Wennekes, Tom,Van Der Stelt, Mario,Van Der Marel, Gijsbert A.,Van Boeckel, Constant A. A.,Aerts, Johannes M. F. G.,Overkleeft, Herman S.
supporting information, p. 9096 - 9104 (2015/03/14)
This work details the evaluation of a number of N-alkylated deoxynojirimycin derivatives on their merits as dual glucosylceramide synthase/neutral glucosylceramidase inhibitors. Building on our previous work, we synthesized a series of d-gluco and l-ido-configured iminosugars N-modified with a variety of hydrophobic functional groups. We found that iminosugars featuring N-pentyloxymethylaryl substituents are considerably more potent inhibitors of glucosylceramide synthase than their aliphatic counterparts. In a next optimization round, we explored a series of biphenyl-substituted iminosugars of both configurations (d-gluco and l-ido) with the aim to introduce structural features known to confer metabolic stability to drug-like molecules. From these series, two sets of molecules emerge as lead series for further profiling. Biphenyl-substituted l-ido-configured deoxynojirimycin derivatives are selective for glucosylceramidase and the nonlysosomal glucosylceramidase, and we consider these as leads for the treatment of neuropathological lysosomal storage disorders. Their d-gluco-counterparts are also potent inhibitors of intestinal glycosidases, and because of this characteristic, we regard these as the prime candidates for type 2 diabetes therapeutics.
Generation and suppression of 3-/4-functionalized benzynes using zinc ate base (TMP-Zn-ate): New approaches to multisubstituted benzenes
Uchiyama, Masanobu,Kobayashi, Yuri,Furuyama, Taniyuki,Nakamura, Shinji,Kajihara, Yumiko,Miyoshi, Tomoko,Sakamoto, Takao,Kondo, Yoshinori,Morokuma, Keiji
, p. 472 - 480 (2008/10/09)
We present full details of our new methods for preparing functionalized benzynes with lithium di-alkyl(2,2,6,6-tetramethylpiperidino)zincate (R 2Zn(TMP)Li) through deprotonative zincation as a key reaction. In this system, by choosing appropriate ligands for the zincate, either regioselective zincation of functionalized haloaromatics or the generation of substituted benzynes can be controlled in good yields with excellent chemoselectivity, using the same substrate. Zincation with tBu 2Zn(TMP)Li followed by electrophilic trapping or zincation with Me2Zn(TMP)Li followed by nucleophilic or diene trapping is shown to be a powerful tool for the chemoselective preparation of 1,2,3-/1,2,4- trisubstituted benzene derivatives. These methods offer far greater generality than previous methods for the synthesis of multifunctionalized benzenes. Computational/theoretical studies of the reaction mechanism of this unique benzyne formation indicated that preferential coordination of the dialkylzinc moiety of zincate to halogen is the reason for the reduced activation energy of the elimination, that is, for the formation of the benzyne. The role of the ligands on Zn in accelerating/decelerating the elimination is also discussed.
