Synthesis of Laevigatin A and E

<p> Ellagitannins is a class of natural polyphenols possessing structural diversity. The diversity grows through oligomerization of monomeric ellagitannins. The oligomerization often arise from formation of C–O digallates as dehydrodigalloyl (DHDG hereafter) group. Despite a wide variety of reported biological activities in ellagitannins, elucidation of their structure–activity relationships have been a problem because of difficulty in obtaining a complete collection of systematically related analogues in nature. Organic synthesis would be useful to solve the problem, if we could develop methodology for synthesizing ellagitannins at will. Among synthetic methods that support the methodology, methods for synthesizing the C–O digallates would be quite important because the C–O digallates are the major element in increase of the structural diversity. Last year, we reported a unified synthetic method for several C–O digallates. Utilizing the unified method, we achieved syntheses of laevigatin A and E.</p><p> Laevigatin A was isolated from the fruits of Rosa laevigata MICHX by Okuda and co-workers in 1989. The structure is 2,3-O-(S)-hexahydroxydiphenoyl (HHDP hereafter)-a-D-glucose, of which anomeric oxygen is esterified with a DHDG group. The synthesis of this compound, which commenced with ethylthio 4,6-di- O-benzyl-b-D-glucopyranoside, composed of 11 steps including diastereoselective formation of the axially chiral HHDP group, a-selective glycosyl esterification with protected gallic acid, application of the unified method described above to the formation of the DHDG group, and adjustments of the oxidation and protection states. All of the synthetic steps were conducted on more than a 1-gram scale. </p><p> The developed synthetic method was applicable to the synthesis of laevigatin E, a dimeric ellagitannin possessing a structural motif similar to that in laevigatin A. </p>