Protecting-Group-Free Synthesis of 2-Deoxy-Aza-Sugars 英文参考文献.docVIP

Molecules 2009, 14, 5298-5307; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Protecting-Group-Free Synthesis of 2-Deoxy-Aza-Sugars Emma Marie Dangerfield 1,2, Catherine Heather Plunkett 1,2, Bridget Louise Stocker 1,* and Mattie Simon Maria Timmer 2,* 1 Malaghan Institute of Medical Research, P.O. Box 7060, Wellington, New Zealand 2 School of Chemical and Physical Sciences, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand * Authors to whom correspondence should be addressed; E-Mail: bstocker@.nz (B.L.S.); mattie.timmer@vuw.ac.nz (M.S.M.T.). Received: 13 November 2009; in revised form: 15 December 2009 / Accepted: 15 December 2009 / Published: 16 December 2009 Abstract: The protecting-group-free asymmetric synthesis of 1,2,4-trideoxy-1,4-imino-L- xylitol is readily achieved in five steps from 2-deoxy-D-ribose and with an overall yield of 48%. Key in this synthesis is the application of our recently developed Vasella-reductive amination and carbamate annulation methodologies to the synthesis of 2-deoxy-aza-sugars. The carbamate annulation occurred with excellent yield and diastereoselectively (20:1 d.r.), in favour of the 3,4-cis isomer. Keywords: aza-sugar; glycosidase inhibitors; asymmetric; reductive amination; carbamate Introduction Aza-sugars (also known as imino-sugars) are mimetics of native sugars whereby the ring oxygen is replaced by a nitrogen atom. Due to their structural similarity to native carbohydrates, aza-sugars are able to act as glycosidase inhibitors and therefore have enormous therapeutic potential in the treatment of a variety of diseases including viral infection, bacterial infection, lysosomal storage disorders, cancer and diabetes [1–9]. Indeed, the use of Zavesca? for the treatment of Gaucher’s disease marked the launch of the first aza-sugar medication [10]. In view of the growing biological importance of aza-su