Spiranic d-gluco-configured N-substituted thiohydantoins as potential enzymatic inhibitors

Gasch, Consolación; Merino-Montiel, Penélope; López, Óscar; Fernández-Bolaños, José G.; Fuentes, José

doi:10.1016/j.tet.2010.09.109

Cited by 15 publications

(5 citation statements)

References 52 publications

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“…salacinol 3, are lead candidates for the treatment of Type 2 diabetes via a-glucosidase inhibition ( Figure 6). 59,60,64,73, Herein we highlight some more recent developments in the field. Salacinol 3 is a potent competitive aglucosidase inhibitor with Ki values of 0.93 (rat intestinal maltase), 0.96 (rat intestinal sucrase), and 1.4 (rat intestinal isomaltase) µM, respectively.…”

Section: Salacinol and Derivativesmentioning

confidence: 99%

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Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors

Simone

Mares

Eveleens

et al. 2018

MRMC

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Glycosidases have important anti-cancer, anti-viral and anti-diabetic properties. This review covers the literature in the past 15 years since our initial review in this journal on "neutral" glycosidase inhibitors lacking a basic nitrogen found in iminosugars and azasugars or inhibitors that are neutral by virtue of being "charge-balanced" (zwitterionic). These structurally diverse inhibitors include lactones, lactams, epoxides such as cyclophellitol, and sulfonium ion derivatives of the natural product salacinol. Synthetic efforts toward cyclophillitol, salicinol and derivatives are also highlighted. Importantly, certain metals can inhibit glycosidases and care must be taken to remove residual catalysts from synthetic material to be tested against these enzymes.

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Section: Salacinol and Derivativesmentioning

confidence: 99%

“…C-2, 62, 63 C-3,[64][65][66][67][68][69][70][71][72] and C-473,74 hydantoin derivatives (highlighted in red in 20, Figure 5) have been synthesised and biologically evaluated in the past 10-15 years. Representative examples of this class of glycosidase inhibitor are highlighted in Figure 5.…”

mentioning

confidence: 99%

Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors

Simone

Mares

Eveleens

et al. 2018

MRMC

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“…[26][27][28][29][30][31] Unlike the generally used OtBu/tBu or Trt side chain protection strategy during Fmoc chemistry polypeptide synthesis, no canonized OH protection is yet accepted for βSAAs, but several alternatives coexist. The large pool comprises Obenzoyl, [32,33] O-acetyl, [18,32,34] acetonide or isopropylidene [4,5,19,21,35,36] derivatives or even free, unprotected OH could be in use [37][38][39] during solution phase peptide synthesis. [40] Thus, the protecting, coupling and selective cleaving of chimeric oligomers remain a challenge.…”

Section: Introductionmentioning

confidence: 99%

Application of Sugar Amino Acids: Flow Chemistry Used for α/β‐Chimera Synthesis

et al. 2021

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Two ring size β-Sugar Amino Acids, βSAAs, Fmoc-RibAFU(ip)-OH and Fmoc-GlcAPU(Me,Bn)-OH, as Lego-elements are introduced to make α/β-chimera peptides by flow-based solid phase peptide synthesis (SPPS). Their synthesis alongside selected αamino acids, αAA, is fine-tuned. The recently published 50 % TFA cleavage protocol of tBu protected shorter (Ser, Asp) and larger aromatic (Tyr, Trp), with bulky side chain protected Arg (Pbf) and Gln(Trt) residues was probed. We found that this milder condition is sufficient to successfully remove both the 1,2-O-isopropylidene from RibAFU(ip) and tBu, Pbf and Trt from the other αAA residues, but to preserve the 2,3-di-O-benzyl protection of GlcAPU(Me,Bn). Note that O-benzyl groups can be subsequently cleaved by HF or catalytic hydrogenation. Tuned protocols allow the efficient synthesis of 16-mer penetratin analogues via continuous flow conditions incorporating either RibAFU(ip) or GlcAPU(Me,Bn) βSAAs. Both acid concentration (50 %/95 %) and type (TFA/HF) allow a versatile protecting group removal and thus, to fine-tune the hydrophilicity and aromaticity of the above building blocks in chimera constructs.

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“…30 Additionally, in the frame of a study of conformationally restricted pseudonucleosides, an N-substituted spirothiohydantoin ring was constructed at the C-3 position of Dglucose, however, such compounds remained inactive against RMGPb. 31 Glucofuranosylidene-spiro-hydantoins 32 as well as some iminosugar derivatives were also studied to show no significant activity except 1,4-dideoxy-1,4-imino-arabinitol (DAB). 33 The phosphorolytic cleavage of glycogen catalyzed by GP is supposed to occur via a glycosyliumion-like transition sate.…”

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confidence: 99%

C-(2-Deoxy-d-arabino-hex-1-enopyranosyl)-oxadiazoles: synthesis of possible isomers and their evaluation as glycogen phosphorylase inhibitors

Bokor

Szennyes

Csupász

et al. 2015

Carbohydrate Research

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Spiranic d-gluco-configured N-substituted thiohydantoins as potential enzymatic inhibitors

Cited by 15 publications

References 52 publications

Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors

Back to (non-)Basics: An Update on Neutral and Charge-Balanced Glycosidase Inhibitors

Application of Sugar Amino Acids: Flow Chemistry Used for α/β‐Chimera Synthesis

C-(2-Deoxy-d-arabino-hex-1-enopyranosyl)-oxadiazoles: synthesis of possible isomers and their evaluation as glycogen phosphorylase inhibitors

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