Trost Barry M, Thiel Oliver R, Tsui Hon-Chung
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA.
J Am Chem Soc. 2003 Oct 29;125(43):13155-64. doi: 10.1021/ja0364118.
A modular approach to the total synthesis of furaquinocins culminated in the total syntheses of furaquinocin A, B, and E. A Pd-catalyzed dynamic kinetic asymmetric transformation (DYKAT) on carbonates derived from Baylis-Hillman adducts, followed by a reductive Heck cyclization allows the enantio- and diastereoselective construction of dihydrobenzofuran 32. Introduction of a double unsatured side chain via Horner-Wadsworth-Emmons reaction and assembly of the naphthoquinone with squaric acid based methodology leads to furaquinocin E. The use of differentially substituted squaric acid derivatives allows the synthesis of three analogues of furaquinocin E. The additional stereocenters in furaquinocin A and B can be introduced with a diastereoselective Sakurai allylation. The stereoselective elongation of the side chain is possible using cross metathesis or ring closing metathesis. The obtained late-stage intermediates were successfully transformed to furaquinocin A and B.
一种用于呋喃喹诺菌素全合成的模块化方法最终实现了呋喃喹诺菌素A、B和E的全合成。对源自贝利斯-希尔曼加合物的碳酸酯进行钯催化的动态动力学不对称转化（DYKAT），随后进行还原 Heck 环化反应，可实现二氢苯并呋喃32的对映选择性和非对映选择性构建。通过霍纳尔-沃兹沃思-埃蒙斯反应引入双不饱和侧链，并采用基于方酸的方法组装萘醌，可得到呋喃喹诺菌素E。使用不同取代的方酸衍生物可合成三种呋喃喹诺菌素E类似物。呋喃喹诺菌素A和B中的额外立体中心可通过非对映选择性的樱井烯丙基化反应引入。使用交叉复分解反应或闭环复分解反应可实现侧链的立体选择性延长。所得到的后期中间体成功转化为呋喃喹诺菌素A和B。
