Synthesis and evaluation of galacto-noeurostegine and its 2-deoxy analogue as glycosidase inhibitors

Abstract

An epimer of the known glycosidase inhibitor noeurostegine, galacto-noeurostegine, was synthesised in 21 steps from levoglucosan and found to be a potent, competitive and highly selective galactosidase inhibitor of Aspergillus oryzae β-galactosidase. Galacto-noeurostegine was not found to be an inhibitor of green coffee bean α-galactosidase, yeast α-glucosidase and E. coli β-galactosidase, whereas potent but non-competitive inhibition against sweet almond β-glucosidase was established. The 2-deoxy-galacto-noeurostegine analogue was also prepared and found to be a less potent inhibitor of the same enzymes.

Stable analogues of nojirimycin – synthesis and biological evaluation of nojiristegine and manno-nojiristegine

“…2). Since galacto-noeurostegine (4-epi-noeurostegine) is not an inihibitor of green coffee beans α-galactosidase, but calystegine and noeurostegine inhibit this enzyme potently, we have previously speculated that the two former azasugars would bind in a nojirimycin (NJ) binding mode 24 placing the ethylene bridge in the same position as nojiristegine (1). The observation, that nojiristegine is not an inhibitor of this enzyme, brings our previous suggestion into question.…”

“…31 Interestingly, the indium mediated Barbier allylation was previously found to be dependent on the C-β stereochemistry in the synthesis of noeurostegine and galacto-noeurostegine (entries 4 and 5), where the aldehyde is flanked by a benzyloxy group (Table 1). 22,24 For these examples, the aldehyde leading to noeurostegine (entry 4) having the same stereochemistry as 7, the S-product dominated, while the opposite was true for the aldehyde leading to galacto-noeurostegine (entry 5).…”

“…The organic phase was washed with water and brine, dried over Na 2 SO 4 , filtered and concentrated under reduced pressure to yield the aldehyde (23) NMR data was in accordance with previously reported values. 43 (4R/S,5R,6S,7R)-5,6,7-Tri-O-benzyl-1,8-nonadiene-4-ol (24). To a stirred solution of the crude aldehyde (23) (0.934 mmol) in 50% aqueous THF (14 mL) was added indium dust (227 mg, 1.98 mmol, 2 eq.)…”

“…These compounds have been christened noeurostegines. [22][23][24] In this report we describe the synthesis, initial inhibitory data and potential antibiotic activity of stable hybrids between nojirimycin/manno-nojirimycin and calystegines. We here refer to these molecules as nojiristegine (1) and manno-nojiristegine (2).…”

Nucleophilic Ring‐Opening of 1,6‐Anhydrosugars: Recent Advances and Applications in Organic Synthesis

“…Direct iodination of the primary alcohol followed by zinc mediated fragmentation afforded the corresponding aldehyde which was transformed in 11 steps to noeurostegine (Scheme 29b). In 2015, the same authors reported the synthesis of its epimer, galacto‐noeurostegine, using a related synthetic strategy [86b] …”