Fucosidase inhibitors

Selected from among their contributions were the first example of a synthetic furanoid iminoalditol, l,4-dideoxy-l,4-imino-D-mannitol (19, Scheme 7) 49 the first synthesis of the powerful L-fucosidase inhibitor l,5-dideoxy-l,5-imino-L-fucitol (20),50 the synthesis and structure confirmation of l,4-dideoxy-l,4-imino-D-arabinitol... 

A L-/wco-related analogue (71) of isofagomine [61], which was recently prepared from D-ribose by Ichikawa et al. following previously established chemistry [63,121], was found to be an a-L-fucosidase inhibitor with Kj 8 pmol/1. No inhibition was found with tetrazole derivatives such as (72) [ 122] obtained from L-gulonolactone. 

Chem. Soc. Chem. Commun. 1983, 835-836. Witczak, Z. J. Boryczewski, D. Thiosugars IV design and synthesis of S-linked fiicoside analogs as a new class of a-L-fucosidase inhibitors. Bioorg. Med. Chem. Lett. 1998, 8, 3265-3268. Kim, K. S. Hurh, E. Y. Youn, J. N. Park, J. I. Dialkyl (l-hydroxyiminoalkyl)phosphonates from 1-bromo-l-nitroalkanes and trialkyl phosphites./. Org. Chem. 1999, 64, 9272-9274. 

Ogawa, S, Maruyama, A, Odagiri, T, Yuasa, H, Hashimoto, H, Synthesis and biological evaluation of alpha-L-fucosidase inhibitors 5a-carba-alpha-L-fucopyranosylamine and related compounds, Eur. J. Org. Chem., 5, 967-974, 2001. 

Fleet, G W J, Shaw, A N, Evans, S V, Fellows, L E, Synthesis from D-glucose of 1,5-dideoxy-1,5-imino-L-fucitol, a potent a-L-fucosidase inhibitor, J. Chem. Soc. Chem., Commun., 841-842, 1985. 

A. Hansen, T. M. Tagmose, and M. Bols, Synthesis of a new potent alpha-fucosidase inhibitor, Chem. Commun., (1996) 2649-2651. 

Defoin et al. has developed the synthesis of hydroxy-ethane derivative 148, a nanomolar a-L-fucosidase inhibitor, starting from chiral nitrone 145, an analog of 5-deoxy-L-lyxose that was derived from o-ribose [67]. Nitrone 145 reacted easily in C2CI4 at 50 °C with phenyl vinyl ether to give cycloadducts 146a and 146b quantitatively in a 85 15 ratio (Fig. 34). The major isomer 146a was converted via pyrrolidine 147 to the C-a-L-fucoside 148 in four steps in an overall yield of 59%. 

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