New Electronic Analogs of the Sialyl Cation:  N-Functionalized 4-Acetamido-2,4-dihydroxypiperidines. Inhibition of Bacterial Sialidases

Parr, Ian B.; Horenstein, Benjamin A.

doi:10.1021/jo9708497

Cited by 32 publications

(23 citation statements)

References 45 publications

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“…[14] As an alternative, a reductive amidation ring-closure was attempted. [15], [16] Alcohol 13 was converted to the ketone 15 in 97 % yield by a Swern oxidation. Treatment of 15 with hydrogen and palladium on carbon under high pressure and temperature did not give conversion, however.…”

Section: Resultsmentioning

confidence: 99%

Enantiospecific Synthesis of 1-Azafagomine

et al. 2000

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For the first time the two enantiomeric forms of the glycosidase inhibitor 1-azafagomine have been synthesised starting from D- and L-xylose. D-Xylose was converted to the 2,3,5-tribenzylfuranose, which upon reductive amination with tert-butyl carbazate gave the protected 1-hydrazino-1-deoxypentitol in high yield. N-acetylation, mesylation of the 4-OH, removal of the Boc group, cyclisation and deprotection gave (+)-1-azafagomine ((+)-1). By a similar sequence of reactions, L-xylose was converted to (-)-1-azafagomine ((-)-1). Enzymatic and other routes to optically pure 1-azafagomine were also studied. Compound (-)-1 is a potent competitive glycosidase inhibitor, while (+)-1 has no biological activity. The inhibition of almond beta-glucosidase by (-)-1 was found to be slow owing to a slow binding step of inhibitor to enzyme, with no subsequent conformational rearrangement. The rate constants for binding and release were found to be 3.3 x 10(4)M(-1)s(-1) and 0.011 s(-1), respectively, yielding Ki = 0.33 microM.

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Section: Resultsmentioning

confidence: 99%

Enantiospecific Synthesis of 1-Azafagomine

et al. 2000

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“…The N-acetyl derivative 59 could be used as starting material for the synthesis of inhibitors of sialidases. [28] Biological Activity Testing …”

Section: Chemistrymentioning

confidence: 99%

The Synthesis and Conformation of Dihydroxypiperidinyl Derivates of Nucleobases as Novel Iminosugar Nucleoside Analogs

Rejman¹,

Pohl²,

Dračínský³

2011

Eur J Org Chem

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An optimized method for the synthesis of an important chiral scaffold, (3S,4R,5R)‐1‐N‐Boc‐3,4‐isopropylidene‐3,4,5‐trihydroxypiperidine, was developed. Using this intermediate, the preparation of various chiral aminodihydroxypiperidines and their transformation into a series of non‐glycosidic, six‐membered azanucleosides was accomplished. NMR conformation analysis of the prepared piperidine azanucleosides revealed a preference for the chair conformation, with the nucleobase fixed in the equatorial position in all cases.

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“…We have decided to develop a new approach where a cyclic sugar backbone 7 was synthesized first and the base was introduced at the latest stage. The synthesis started from readily available furanose building blocks 2 and 3 16,17 (Scheme 1). The phosphotriester methodology 6,18 was used to produce dimer 5, which was deprotected with ceric ammonium nitrate (CAN) in methanol 19 (5 → 6).…”

Section: Figure 1 C-di-gmpmentioning

confidence: 99%