Synthesis and Comparative Study of Homoisofagomines and Analogues as Glycosidase Inhibitors

Abstract

The synthesis of polyhydroxyazepanes and their corresponding lactams has been carried out by use of Grubbs cyclisation, to yield the azepane scaffolds, as a key step. A comparative study of glycosidase inhibition by the azepanes and the corresponding lactams with varying stereochemical dispositions, number of hydroxy groups, and side chain structures was carried out.

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…256) [665], homoisofagomines and analogs [666], cycloheptenes derived from two proline units [667], tuberostemospiroline and stemona lactone R [668], a cyclic α-amino acid derivative (e.g. 257) [669], tetrapetolone (through a diastereoselective RCM employing a substrate with diastereotopic vinyl groups using a chiral molybdenum complex catalyst) [670], and tricyclic IAP inhibitors (e.g.…”

Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation

“…The seven-membered, N -heterocyclic azepane scaffold is a biologically active epitope and useful building block in the construction of novel glycosidase inhibitors [ 1 , 2 , 3 , 4 , 5 ], anticancers [ 6 , 7 , 8 , 9 , 10 ], antidiabetics [ 11 , 12 , 13 , 14 , 15 ], antivirals [ 16 , 17 ] and DNA minor groove-binding agents [ 18 , 19 , 20 ]. In particular, azepanols and oxo-azepines have received much recent attention as useful epitopes in both materials and medicinal chemistry due to the unique flexibility of the seven-membered ring and resultant spatial distribution of oxygen substituents.…”

“…This 3 10 helical conformation was found to be stabilized by key intramolecular hydrogen bonds between the 2-oxo-azepine ketone oxygen and amino acid residues [ 22 , 23 ]. Vankar et al in 2014 reported syn -dihydroxyazepane iv as a potent and selective inhibitor of jack bean α-mannosidase, while its epimer v was two orders of magnitude less active towards this enzyme [ 2 ]. In a recent landmark example, Spiegel et al prepared glucosepane enantioselectively from oxo-azepine vi , yielding a guanidine-containing oxo-azepine ( Scheme 1 b) [ 24 ].…”