Lewis Chad A, Chiu Anna, Kubryk Michele, Balsells Jaume, Pollard David, Esser Craig K, Murry Jerry, Reamer Robert A, Hansen Karl B, Miller Scott J
Department of Chemistry, Yale University, New Haven, CT 06520, USA.
J Am Chem Soc. 2006 Dec 27;128(51):16454-5. doi: 10.1021/ja067840j.
The chirality of biological receptors often requires syntheses of therapeutic compounds in single enantiomer form. The field of asymmetric catalysis addresses enantioselective synthesis with chiral catalysts. Chemical differentiation of sites within molecules that are separated in space by long distances presents special challenges to chiral catalysts. As the distance between enantiotopic sites increases within a substrate, so too may the requirements for size and complexity for the catalyst. The extreme of catalyst complexity could be defined by macromolecular enzymes and their amazing capacity to effect stereospecific reactions over long distances between reactive sites and enzyme-substrate contacts. We report here a synthetic, miniaturized enzyme mimic that catalyzes a desymmetrization reaction over a very long distance.
生物受体的手性通常要求以单一对映体形式合成治疗性化合物。不对称催化领域致力于使用手性催化剂进行对映选择性合成。分子中在空间上被长距离分隔的位点的化学区分对手性催化剂提出了特殊挑战。随着底物中对映异位点之间的距离增加,对催化剂的尺寸和复杂性的要求也可能增加。催化剂复杂性的极端情况可以由大分子酶及其在反应位点与酶 - 底物接触之间的长距离上实现立体特异性反应的惊人能力来定义。我们在此报告一种合成的、小型化的酶模拟物,它能在非常长的距离上催化去对称化反应。