ABSTRACT
Ellagitannins are a family of polyphenols containing more than 1,000 natural products. Nearly 40% of these compounds contain a highly oxygenated diaryl ether that is one of the most critical elements to their structural diversity. Here, we report a unified strategy for the synthesis of highly oxygenated diaryl ethers featured in ellagitannins. The strategy involves oxa-Michael addition of phenols to an orthoquinone building block, with subsequent elimination and reductive aromatization. The design of the building block--a halogenated orthoquinone monoketal of gallal--reduces the usual instability of orthoquinone and controls addition/elimination. Reductive aromatization is achieved with perfect chemoselectivity in the presence of other reducible functional groups. This strategy enables the synthesis of different diaryl ethers. The first total synthesis of a natural ellagitannin bearing a diaryl ethers is performed to demonstrate that the strategy increases the number of synthetically available ellagitannins.
Subject(s)
Chemistry Techniques, Synthetic/methods , Ethers/chemical synthesis , Hydrocarbons, Aromatic/chemical synthesis , Hydrolyzable Tannins/chemistry , Oxygen/chemistry , Ethers/chemistry , Hydrocarbons, Aromatic/chemistry , Molecular StructureABSTRACT
A proposed structure of roxbin B was synthesized. For the synthesis, a new synthetic method for the preparation of the hexahydroxydiphenoyl (HHDP) bridge was developed that involved the stepwise esterification of axially chiral HHDP acid anhydride. The synthesized compound was not identical to the natural roxbin B.
Subject(s)
Glucosides/chemistry , Glucosides/chemical synthesis , Hydrolyzable Tannins/chemistry , Hydrolyzable Tannins/chemical synthesis , Esterification , Molecular Structure , Rosa/chemistryABSTRACT
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.
