Drug creation involving hybrid type of low molecular weight biomolecules as lead compounds

迄今为止，对新药物先导化合物的研究主要集中在生物化合物的单一组分上，而不是杂合组分。我们开始了我们的项目，开发最有效和实用的合成方法的生物杂化化合物，包括氨基酸，糖和核酸。通过与烯烃相连的肟醚的自由基加成-环化路线，提出了合成氨基酸及相关肽的新方法。产物顺利转化为β-氨基酸。我们还研究了不受保护的天然糖的自由基反应对糖部分的构建。与羰基连接的肟醚的锡基自由基加成-环化反应顺利进行，得到环氨基醇，并转化为氨基环醇。发现自由基反应通过最稳定的过渡态进行，涉及最小的1,3 -烯丙基菌株。通过1,2 - wittig重排和不对称羟基化两个关键反应完成了原位合成。

Research for exploring new lead compounds for new drugs has focused to one component of biological compounds and not to hybrid components so far. We started our project to develop the most efficient and practical synthetic method for biological hybrid compounds which consist of amino acids, sugars, and nucleic bases.New synthetic method for amino acids and the related peptides has been developed via the route involving radical addition-cyclization of oxime ethers connected with olefins. The products were converted smoothly into β-amino acids.We also investigated construction of sugar parts by the radical reactions of the unprotected natural sugars. Stannyl radical addition-cyclization of oxime ethers connected with the carbonyl group proceeded smoothly to afford cyclic amino alcohols which were converted into aminocyclitols. The radical reaction was found to proceed via the most stable transition state involving minimum 1, 3-allylic strain.Formal synthesis of Dysiherbine was completed via two key reactions which are 1, 2-Wittig rearrangement and asymmetric hydroxylation respectively.