Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Nat Chem. 2013 Sep;5(9):790-5. doi: 10.1038/nchem.1726. Epub 2013 Aug 11.
Carbohydrates and natural products serve essential roles in nature, and also provide core scaffolds for pharmaceutical agents and vaccines. However, the inherent complexity of these molecules imposes significant synthetic hurdles for their selective functionalization and derivatization. Nature has, in part, addressed these issues by employing enzymes that are able to orient and activate substrates within a chiral pocket, which increases dramatically both the rate and selectivity of organic transformations. In this article we show that similar proximity effects can be utilized in the context of synthetic catalysts to achieve general and predictable site-selective functionalization of complex molecules. Unlike enzymes, our catalysts apply a single reversible covalent bond to recognize and bind to specific functional group displays within substrates. By combining this unique binding selectivity and asymmetric catalysis, we are able to modify the less reactive axial positions within monosaccharides and natural products.
碳水化合物和天然产物在自然界中起着重要作用，也是药物制剂和疫苗的核心支架。然而，这些分子的固有复杂性对它们的选择性功能化和衍生化提出了重大的合成挑战。自然界在一定程度上通过使用能够在手性口袋中定向和激活底物的酶来解决这些问题，这极大地提高了有机转化的速率和选择性。在本文中，我们表明，类似的邻近效应可以在合成催化剂的背景下加以利用，从而实现复杂分子的通用和可预测的选择性官能化。与酶不同，我们的催化剂使用单个可逆共价键来识别和结合底物中特定的功能组显示。通过结合这种独特的结合选择性和不对称催化，我们能够修饰单糖和天然产物中反应性较低的轴向位置。
