Asymmetric synthesis of bioactive azapyranose derivatives

氮杂糖衍生物有望成为一类与抑制糖基化酶有关的新型药物。1.研究了异法戈明和帕罗西汀的合成。这些氮杂糖具有潜在的抗HIV和抗阿尔茨海默病的活性，可由化学-酶法合成的N-Boc-γ-苄氧甲基-α，β-不饱和-δ-内酰胺1制备。我们实现了异法戈明的合成，但不幸的是，1的双羟基化的非对映选择性低。另一方面，对氟苯基格氏试剂与1的Michael加成反应显示出高的非对映选择性和化学产率。通过Michael加成反应，以较好的收率得到了手性帕罗西汀。2.最近我们报道了一种重要的手性结构单元--γ-乙酰氧基-α，β-不饱和-γ-内酰胺2的合成。研究了以手性内酰胺2为原料合成（-）-2-epilentiginosine的方法。2的双羟基化，然后烯丙基化顺利进行。烯丙基化产物经转化得到（-）-2-epilentiginosine，其光谱数据与真实数据一致。

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.