Asymmetric synthesis of bioactive azapyranose derivatives

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Azasugar derivatives have been anticipated to be new designed pharmaceuticals which are related to the inhibition of glycosidase.1.Syntheses of isofagomine and paroxetine were investigated. These azasugars potentially have anti-HIV and anti-Alzheimer activities and could be prepared from N-Boc-γ-benzyloxymethyl-α,β-unsaturated-δ-lactam 1, which was produced by chemo-enzymatic process. We achieved the synthesis of isofagomine, however unfortunately, the diastereoselectivity in dihydroxylation of 1 was low. On the other hand, Michael addition of p-fluorophenyl-Grignard reagent to 1 showed high diastereoselectivity and chemical yield. Transformations of Michael adduct gave the chiral paroxetine in good yield.2.Recently we reported the synthesis of a chiral γ-acetoxy-α,β-unsaturated-γ-lactam 2, which was an important chiral building block. The synthesis of (-)-2-epilentiginosine using the chiral lactam 2 was examined. Dihydroxylation of 2, then allylation smoothly proceeded. Transformations of allylation-product gave (-)-2-epilentiginosine, its spectral data was identical with authentic data.