The nitroaldol route towards nitro-, amino-, and iminopolyols. Prerequisites for efficient addition with high diastereoselectivity

Looking for more efficient access to amino-tride-oxyhexoses like L-acosamin e (glycone part of antitumour antibiotics) and anisomycin (antibiotic agent ), the nitroaldol route was considered. The silyl nitronate version with pr otected lactaldehyde and 3-nitropropanal proved to be only moderately succe ssful, tempting a broader study of structural effects on the diastereoselec tivity of more complex cases. With chiral alpha-oxy-aldehydes (C-3, C-4) an d chiral alpha-X-nitroalkanes high selectivities (up to > 95% for only one of the four diastereomers expected) may be achieved. Double diastereodiffer entiation is met only with the cases of two 4-(nitromethyl)-1,3-dioxanes (4 -nitrobutane-1,3-diol benzylidene acetals). Several examples of the synthes es of 5- and 6-membered iminoglycitols (potential or known glycosidase inhi bitors) from these nitropolyols, via reduction of the nitro group and N-cyc lization, are presented. Finally, a superior solution for the initial probl em, the synthesis of L-acosamine, was elaborated when the effects of solven t and temperature on the above (C-3+C-3)-case were elucidated. These result s altogether are taken to derive guidelines for achieving high diastereosel ectivity in nitroaldol additions, where two new stereocentres are formed in processes that involve simple and induced or double diastereoselection.