Abstract:Indole-3-acetonitrile-4-methoxy-2-C-β-D-glucopyranoside (1), a novel C-glycoside from Isatis indigotica with important cytotoxic activity, has been prepared in ten steps from ethynyl-β-C-glycoside 3 and 2-iodo-3-nitrophenyl acetate 6. Key steps in the synthesis include a Sonogashira coupling and a CuI-mediated indole formation. NMR spectrocopic data for synthetic 1 differs from that reported for the natural product. A revised structure for the natural product, containing an alternate carbohydrate substituent, … Show more
“…Furthermore, a facile one-pot multicatalytic synthesis was achieved by combining our strain-release glycosylation with a Cu-catalyzed non-CLICK [3 + 2]-cycloaddition of alkynes with o -iodotosylanilines to generate a C2- indole glycoside 32 (Fig. 3d ) which opens up a route towards related indolyl-glycosides with anti-cancer activities 66 , 67 . Fig.…”
The utility of thiourea catalysis in selective glycosylation strategies has gained significant momentum lately due to its versatility in hydrogen bonding or anionic recognition activation modes. The use of these non-covalent interactions constitute a powerful means to construct glycosidic linkages as it mimics physiologically occurring glycosyltransferases. However, glycosyl donor activation through the currently employed catalysts is moderate such that, in general, catalyst loadings are rather high in these transformations. In addition, thiourea catalysis has not been well explored for the synthesis of furanosides. Herein, we demonstrate an ultra-low loadings stereoselective and stereospecific thiourea catalyzed strain-release furanosylation and pyranosylation strategy. Our ultra-low organocatalyzed furanosylation enables a multicatalytic strategy, which opens up a unique avenue towards rapid diversification of synthetic glycosides. In-situ NMR monitoring unravel insights into unknown reaction intermediates and initial rate kinetic studies reveal a plausible synergistic hydrogen bonding/Brønsted acid activation mode.
“…Furthermore, a facile one-pot multicatalytic synthesis was achieved by combining our strain-release glycosylation with a Cu-catalyzed non-CLICK [3 + 2]-cycloaddition of alkynes with o -iodotosylanilines to generate a C2- indole glycoside 32 (Fig. 3d ) which opens up a route towards related indolyl-glycosides with anti-cancer activities 66 , 67 . Fig.…”
The utility of thiourea catalysis in selective glycosylation strategies has gained significant momentum lately due to its versatility in hydrogen bonding or anionic recognition activation modes. The use of these non-covalent interactions constitute a powerful means to construct glycosidic linkages as it mimics physiologically occurring glycosyltransferases. However, glycosyl donor activation through the currently employed catalysts is moderate such that, in general, catalyst loadings are rather high in these transformations. In addition, thiourea catalysis has not been well explored for the synthesis of furanosides. Herein, we demonstrate an ultra-low loadings stereoselective and stereospecific thiourea catalyzed strain-release furanosylation and pyranosylation strategy. Our ultra-low organocatalyzed furanosylation enables a multicatalytic strategy, which opens up a unique avenue towards rapid diversification of synthetic glycosides. In-situ NMR monitoring unravel insights into unknown reaction intermediates and initial rate kinetic studies reveal a plausible synergistic hydrogen bonding/Brønsted acid activation mode.
“…The carbohydrate coupling partner ( 2 ) required for the C -glycosylation reaction may be prepared in 72% overall yield from dextrose as previously described. 7 Treatment of 2a with a 1:1 solution of trifluoroacetic anhydride and CH 2 Cl 2 for 30 min, followed by evaporation and combination with commercially available 1,2,3-trimethoxybenzene (1.5 equiv) and BF 3 ·OEt 2 (1.1 equiv) in CH 2 Cl 2 at room temperature for 30 min, afforded coupled product 4 (>20:1 β:α at C.1) in 62% yield (Scheme 1 ). 8 Interestingly, 2- O -benzyl-1,3-dimethoxybenzene ( 3b ) was not a suitable partner for the C -glycosylation reaction, undergoing rapid decomposition in the presence of either BF 3 ·OEt 2 or TMSOTf.…”
The 3,3′-di-O-methyl derivative (15) of the bis-C-aryl glycoside natural product ardimerin (1) has been synthesized in eleven steps from 2,3,4,6-tetrabenzylglucose (2) and 1,2,3-trimethoxybenzene (3). Key steps in the synthesis involve a Lewis-acid mediated Friedel Crafts-type glycosylation and a Yamaguchi lactonization under Yonemitsu conditions. 3,3′-Di-O-methyl ardimerin aggregates in aqueous solutions at concentrations greater than 1 μM, and both UV and fluorescence binding studies indicate that 15 has a low affinity for duplex DNA.
“…Interestingly, a bis‐alkyne derivative selectively gave the mono‐indolyl‐ C ‐glycoside. Yepremyan and Minehan independently used Sonogashira and hydroamination reactions in a stepwise sequence for the total synthesis of indole‐3‐acetonitrile‐4‐methoxy‐2‐C‐β‐ d ‐glucopyranoside …”
Section: Modification Of Sugarsmentioning
confidence: 95%
“…Yepremyana nd Minehani ndependently used Sonogashiraa nd hydroamination reactions in as tepwise sequencef or the total synthesis of indole-3-acetonitrile-4-methoxy-2-C-b-d-glucopyranoside. [79] Annulated carbohydrate products are commonly found in naturallyoccurring and biologically active compounds. One approach for the efficient synthesis of annulated carbohydrate products is based on ring-closing-metathesis.…”
Homogeneous catalysis plays an important and ubiquitous role in the synthesis of simple and complex molecules, including drug compounds, natural products, and agrochemicals. In recent years, the wide-reaching importance of homogeneous catalysis has made it an indispensable tool for the modification of biomolecules, such as carbohydrates (sugars), amino acids, peptides, nucleosides, nucleotides, and steroids. Such a synthetic strategy offers several advantages, which have led to the development of new molecules of biological relevance at a rapid rate relative to the number of available synthetic methods. Given the powerful nature of homogeneous catalysis in effecting these synthetic transformations, this Focus Review has been compiled to highlight these important developments.
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