The synthesis of corilagin was achieved by the integration of the development of the oxidative coupling of the symmetrically protected gallates and the temporarily ring-opened synthetic route for the 3,6-hexahydroxydiphenoyl (HHDP) bridge. This is the first total synthesis of the 1C4/B-ellagitannins, which contain ring-flipped glucose.

This paper describes a total synthesis of (-)-strictinin, an ellagitannin that is 1-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl (HHDP)-β-D-glucose. In the study, total efficiency of the synthesis was improved to produce a 78% overall yield in 13 steps from D-glucose. In the synthesis, formation of the 4,6-(S)-HHDP bridge including the 11-membered bislactone ring was a key step, in which intramolecular aryl-aryl coupling was adopted. The coupling was oxidatively induced by CuCl2-n-BuNH2 with perfect control of the axial chirality, and the reaction conditions of this coupling were optimized thoroughly to achieve the quantitative formation of the bridge.

A reliable method for synthesizing each enantiomer of the hexahydroxydiphenoyl (HHDP) compounds has been developed. The synthesis involved atropselective construction of the aryl-aryl bond of the HHDP compounds. This construction relied on the CuCl(2)·n-BuNH(2)-mediated intramolecular coupling of bis(4-O-benzylgallate) on two simple chiral auxiliaries, both of which were derived from l-(+)-tartaric acid. The coupling reaction realized complete or near-perfect atropselectivity. The two auxiliaries induced opposite axial chirality despite their identical origin. The diastereoselectivities of these couplings were probably controlled kinetically. Modifications of the free phenolic hydroxy groups and the carbonyl groups in the resulting HHDP compounds demonstrated the potential derivatization of a wide variety of HHDP analogues.

No abstract

The total synthesis of mallotusinin, which bears a tetrahydroxydibenzofuranoyl (THDBF) bridge between the 2oxygen and 4-oxygeno fg lucose on corilaginw ith a3 ,6-O-(R)-hexahydroxydiphenoyl (HHDP) bridge, is described. The key features of the total synthesis are:1)improvements of our previously reported method to synthesize corilagin; 2) establishment of the THDBF skeleton via an unusuali ntramolecular S N Ar reactionofanHHDP analogue, and 3) the application of at wo-step bislactonization strategy for aH HDP bridge construction into the 2,4-O-THDBF bridge. Oxidative phenolc oupling of 1,2,4-orthoacetyl-3,6-di-(4-O-benzylgalloyl)-ad -glucopyranose and the orthoester cleavage of the couplingp roduct without the pyranose-furanose ring transformation are keyr eactions for the improved synthesis of corilagin,w hich enabled the adequate supply of ac orilagin precursor that was required to develop the mallotusinin synthesis. These established methods are expected to help develop the synthesis of other ellagitannins with ab ridge between the two oxygens of corilagin.