Synthesis of Fusion‐Isomeric Imidazopyridines and Their Evaluation as Inhibitors of <i>syn</i>‐ and <i>anti</i>‐Protonating Glycosidases

Mohal, Narinder; Vasella, Andrea

doi:10.1002/hlca.200490287

Cited by 6 publications

(3 citation statements)

References 71 publications

(40 reference statements)

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“…Data in agreement with the literature 4,6,7,10 (ent-5). 4,6,7,10 Yield: 655 mg (57%); yellow oil; R f (hexanes/EtOAc, 1:1) = 0.70. Data in agreement with the literature 4,6,7,10 (ent-6).…”

Section: General Procedures For the 23-di-o-isopropylidene Protectionsupporting

confidence: 91%

“…The products were purified and isolated by flash silica column chromatography with hexanes/EtOAc as the eluent. 4,6,7,10 Yield: 520 mg (51%); yellow oil; R f (hexanes/EtOAc, 1:1) = 0.55. Data in agreement with the literature 4,6,7,10 (ent-5).…”

Section: General Procedures For the 23-di-o-isopropylidene Protectionmentioning

confidence: 99%

“…4,6,7,10 Yield: 520 mg (51%); yellow oil; R f (hexanes/EtOAc, 1:1) = 0.55. Data in agreement with the literature 4,6,7,10 (ent-5). 4,6,7,10 Yield: 655 mg (57%); yellow oil; R f (hexanes/EtOAc, 1:1) = 0.70.…”

Section: General Procedures For the 23-di-o-isopropylidene Protectionmentioning

confidence: 99%

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Investigations towards the Synthesis of 5-Amino-l-lyxofuranosides and 4-Amino-lyxopyranosides and NMR Analysis

Diez‐Martinez¹,

Krishnamurthy²

2017

SynOpen

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The reactivity of trifluoromethanesulfonyl esters derived from L-lyxofuranosides and L-lyxopyranosides was investigated with various 5-aminopyrimidines as nucleophiles with the expectation to synthesize N-substituted 5-amino-ribosugars. The lyxopyranoside forms were found to be unreactive, while the lyxofuranoside forms were found to be reactive with 5-aminopyrimidines, yielding novel N-substituted 5-amino-lyxofuranosides. We report on the synthesis of these novel N-substituted lyxofuranosides and the systematic analyses of NMR data that demonstrate trends within each series: furano-, pyrano-, β-and α-anomers of L-lyxose and β-D-ribopyranoside forms. The data call for caution when identifying these monosaccharides in isomeric mixtures. Key words L-lyxofuranoses, L-lyxopyranoses, D-ribopyranoses, conformation analysis, heterocycles, NMR spectroscopyIn our research exploring the self-assembly properties of alternative recognition elements such as 5-aminouracil and 2,4,5-triaminopyrimidine substituted-pyrrolidines, it was necessary to develop new N-substituted 4-amino-D-ribofuranose sugars. [1][2][3] We proposed the corresponding Llyxopyranose derivatives as outlined in Scheme 1 as intermediates en route to the final pyrrolidine compounds. This synthetic approach is based on the fact that nucleophiles can attack the C(4) position of a substituted lyxopyranose sugar (with a good leaving group at the C(4)-position) through a bimolecular nucleophilic substitution (S N 2) displacement, resulting in the corresponding ribopyranose framework. [4][5][6][7] However, the synthesis of N-substituted 4-amino-D-ribopyranose derivatives proved problematic with amino pyrimidine heterocycles, presumably due to the poor nucleophilicity of these alternative amino nucleobases. For comparison, we also studied the S N 2 reaction with the L-lyxofuranosyl series with the awareness that 5-amino-heterocycles may react more readily at a primary carbon. When comparing the results of the L-lyxopyranose and L-lyxofuranose series, we found that there could be some uncertainty in the assignments as α/β anomeric mixtures of alcohols derived from L-lyxose when they are actually furanoside/pyranoside mixtures. 8 To clarify this issue, we have synthesized, measured NMR spectra and contrasted the chemical shift trends of the furanosyl and pyranosyl Llyxose series -both from this work and those in the literature -and came to the conclusion that identifying the minor compound in isomeric mixtures of monosaccharides can be crucial and should always rely on accurate identification based on corroborating NMR techniques.

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“…Data in agreement with the literature 4,6,7,10 (ent-5). 4,6,7,10 Yield: 655 mg (57%); yellow oil; R f (hexanes/EtOAc, 1:1) = 0.70. Data in agreement with the literature 4,6,7,10 (ent-6).…”

Section: General Procedures For the 23-di-o-isopropylidene Protectionsupporting

confidence: 91%

Section: General Procedures For the 23-di-o-isopropylidene Protectionmentioning

confidence: 99%

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Investigations towards the Synthesis of 5-Amino-l-lyxofuranosides and 4-Amino-lyxopyranosides and NMR Analysis

Diez‐Martinez¹,

Krishnamurthy²

2017

SynOpen

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Synthesis of a Fusion‐Isomeric Cellobionoimidazole and Its Evaluation against the syn‐Protonating Glycosidase Cel7A

Mohal

Bernet

Vasella

2005

Helvetica Chimica Acta

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The fusion-isomeric cellobinoimidazole 2, a potential inhibitor of the syn-protonating b-glycosidase Cel7A, was synthesised by Koenigs-Knorr glycosylation of the a-D-arabinopyranoside 32, followed by selective hydrolysis. Glycosylation of 32 with acetobromoglucose 6 proceeded with poor diastereoselectivity, giving the desired 1,3-linked b-D-disaccharide 35 as minor product, besides the major 1,3-linked a-D-disaccharide 36. Hg 2+ -Promoted glycosylation of 32 led predominantly to the 1,2-ortho ester 33. Sequential removal of the silyl, acetyl, and allyl groups of 35 led to a 45 : 55 equilibrium mixture 2 and the manno-configured isomer 39. Similarly, deprotection of 36 gave a mixture of the maltonoimidazole 42 and the manno-configured isomer 43. According to a known protocol, the glycosyl acceptor 32 was synthesised in eleven steps and an overall yield of 8 -13% from D [17]. The inhibitory inactivity may be due to the requirement of Cel7A for di-or oligosaccharide substrates, and/or to an unsuitable position of the glycosidic heteroatom. An appreciation of these factors requires the synthesis of at least a disaccharide analogue 2 of 1 [18]. As the isomeric cellobionoimidazole 3 [19] is a potent inhibitor of the anti-protonating b-glycosidase Cel5A of family 5, a comparison of the inhibitory activity of 2 and 3 promised to be meaningful. We decided to synthesise this fusion-isomeric cellobionoimidazole 2.

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Synthesis of Glycaro‐1,5‐lactams and Tetrahydrotetrazolopyridine‐5‐carboxylates: Inhibitors of β‐D‐Glucuronidase and α‐L‐Iduronidase

Pabba

Rempel

Withers

et al. 2006

Helvetica Chimica Acta

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The known glucaro-1,5-lactam 8, its diastereoisomers 9 -11, and the tetrahydrotetrazolopyridine-5-carboxylates 12 -14 were synthesised as potential inhibitors of b-D-glucuronidases and a-L-iduronidases. The known 2,3-di-O-benzyl-4,6-O-benzylidene-D-galactose (16) was transformed into the D-galactaroand L-altraro-1,5-lactams 9 and 11 via the galactono-1,5-lactam 21 in twelve steps and in an overall yield of 13 and 2%, respectively. A divergent strategy, starting from the known tartaric anhydride 41, led to the D-glucaro-1,5-lactam 8, D-galactaro-1,5-lactam 9, L-idaro-1,5-lactam 10, and L-altraro-1,5-lactam 11 in ten steps and in an overall yield of 4 -20%. The anhydride 41 was transformed into the L-thre-A C H T U N G T R E N N U N G uronate 46. Olefination of 46 to the (E)-or (Z)-alkene 47 or 48 followed by reagent-or substrate-controlled dihydroxylation, lactonisation, azidation, reduction, and deprotection led to the lactams 8 -11. The tetrazoles 12 -14 were prepared in an overall yield of 61 -81% from the lactams 54, 28, and 67, respectively, by treatment with Tf 2 A C H T U N G T R E N N U N G O and NaN 3 , followed by saponification, esterification, and hydrogen-A C H T U N G T R E N N U N G olysis. The lactams 8 -11 and 40 and the tetrazoles 12 -14 are medium-to-strong inhibitors of b-D-glucuronidase from bovine liver. Only the L-ido-configured lactam 10 (K i = 94 mM) and the tetrazole 14Introduction. -b-D-Glucuronidases (EC 3.2.1.31, family 2) 1 ) and a-L-iduronidases (EC 3.2.1.76, family 39) remove glycuronic acid residues from the non-reducing end of glycosaminoglycans such as chondroitin sulfate and hyaluronic acid.

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Synthesis of Fusion‐Isomeric Imidazopyridines and Their Evaluation as Inhibitors of syn‐ and anti‐Protonating Glycosidases

Cited by 6 publications

References 71 publications

Investigations towards the Synthesis of 5-Amino-l-lyxofuranosides and 4-Amino-lyxopyranosides and NMR Analysis

Investigations towards the Synthesis of 5-Amino-l-lyxofuranosides and 4-Amino-lyxopyranosides and NMR Analysis

Synthesis of a Fusion‐Isomeric Cellobionoimidazole and Its Evaluation against the syn‐Protonating Glycosidase Cel7A

Synthesis of Glycaro‐1,5‐lactams and Tetrahydrotetrazolopyridine‐5‐carboxylates: Inhibitors of β‐D‐Glucuronidase and α‐L‐Iduronidase

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