開催日: 2017/09/20 - 2017/09/22
Carthamin (1), a Japanese traditional red pigment, is a constituent of the flower petals of safflower. After a long-standing structural investigation, the currently accepted planar structure was independently proposed by Obara and Matsumoto. However, its stereochemistry was deduced by comparison of the synthetic analogues by Sato, and the total synthesis has remained unachieved. The structural features include 1) C-glycoside composed of a D-glucose and a quinol, 2) the stereogenic center associated with the tert-alcohol, 3) the dimer of the C-glycosyl quinochalcone units flanked by one carbon, and 4) a highly conjugated system that is the origin of the color. Charmed by such a complex and unusual structure, we became interested in the total synthesis. Herein, we will report the first total synthesis of 1 through the construction of the quinol C-glycoside structure by means of oxidative dearomatization. As a potential access to the C-glycosyl quinochalcone as the key intermediate for the dimerization, we initially studied the oxidative dearomatization of C-glycosyl phenols by using hypervalent iodine reagent. It turned out that choice of the 2-O-protecting group of the sugar moiety was crucial for the success of this conversion. By employing the 2-O-acyl protection, the oxidative dearomatization reaction proceeded smoothly, giving the desired dearomatization product in an excellent yield. Through this first-generation synthetic venture, we noted a photo-lability of the geometry of the chalcone double bond. A good news was that the impaired geometry could be corrected to the right (E)-geometry at the stage of advanced intermediates with an internal hydrogen bonding, undergoing the one-way photo-isomerization. Toward the stereo-controlled generation of the quaternary center, we planned the second-generation approach based on a group-selective functionalization of pseudo-Cs-symmetric cyclic dienone derivative. Pleasingly, the group-selective bromoacetoxylation enabled the projected desymmetrization, giving the corresponding bromodienone with the requisite stereochemistry. Further transformation allowed construction of the key C-glycosyl quinochalcone structure in a stereo-defined manner. Assembly of two C-glycosyl quinochalcone units to the central one carbon followed by global deprotection by using formic acid gave the targeted compound 1. The synthetic material was fully identical in all respects with the authentic specimen.