Nicolaou K C, Gray David L F, Tae Jinsung
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Am Chem Soc. 2004 Jan 21;126(2):613-27. doi: 10.1021/ja030498f.
A number of naturally occurring substances, including hamigerans, contain ring systems which are fused to an aromatic nucleus. A general and streamlined method for the construction of such benzannulated bi- and polycyclic carbon frameworks has been developed, and its scope and limitations were explored. On the basis of the photoenolization of substituted benzaldehydes and subsequent Diels-Alder (PEDA) trapping of the generated hydroxy-o-quinodimethanes, this method was optimized to set the stage for the total synthesis of several naturally occurring members of the hamigeran class. Specifically, the developed synthetic technology served as the centerpiece process for the successful asymmetric synthesis of hamigerans A (2), B (3), and E (7). In addition to the PEDA reactions, several other novel reaction processes are described, including a high-yielding decarbonylative ring contraction and an oxidative decarboxylation of a hydroxyl beta-keto ester to afford an alpha-diketone. A number of analogues of these biologically active natural products were also prepared by application of the developed technology.
许多天然存在的物质，包括哈米吉多坦类化合物，都含有与芳核稠合的环系。已经开发出一种构建此类苯并稠合双环和多环碳骨架的通用且简化的方法，并对其范围和局限性进行了探索。基于取代苯甲醛的光烯醇化以及随后对生成的羟基邻醌二甲烷的狄尔斯-阿尔德（PEDA）捕获，对该方法进行了优化，为哈米吉多坦类几种天然存在的成员的全合成奠定了基础。具体而言，所开发的合成技术是成功不对称合成哈米吉多坦A（2）、B（3）和E（7）的核心过程。除了PEDA反应外，还描述了其他几种新颖的反应过程，包括高产率的脱羰环收缩反应以及羟基β-酮酯的氧化脱羧反应以生成α-二酮。通过应用所开发的技术，还制备了这些生物活性天然产物的许多类似物。
