Abstract
Triterpene or steroidal oligosaccharides so called saponin is an important group of natural product on the basis of a variety of biological activities. However little total synthesis have achieved probably due to the interruption between sugar chemistry and terpenoid synthesis. We have recently reported the total synthesis of sweet tasting diterpene glycosides, baiyunoside and analogs, by means of a biomimetic olefin cyclization followed by glycosylations. Then we have developed a very simple thermal glycosylation procedure, which is particularly useful for the synthesis of O-α-rhamnose linkage. Now we wish to disclose herein the novel synthetic study of an intensely sweet tasting saponin, osladin (1) isolated from rhizomes of Polypodium vulgare (Polypodiaceae) by Sorm and co-workers in 1971, as the extension of our series of synthetic program. However the stereochemistry of osladin was not yet fully established. Although the stereochemistry of aglycon are confirmed by partial synthesis, stereochemistry at C-26 is unknown and two kinds of O-rhamnoside bonds are only deduced to be α. Thus we have to confirm the stereochemistry throughout this synthetic study. Points of the synthetic ideas are 1) sugar residues are regarded as protecting groups of C-3 and 26 oxygen functionalities and are introduced at relatively earlier stage of synthesis, 2) stereochemistry of C-5, 22, 25, and 26 must be controlled by stereoselective reactions and other asymmetric centers will be able to derive from starting material, stigmasterol, 3) the difficulty of glycosylation into the hemiacetal hydroxyl at C-26 have to be overcome by a stereoselective manner. Synthesis were started from easily available aldehyde 2 as a degradation product of stigmasterol. To the lactone alcohol 5, a novel β-selective glycosylation to give 7 was achieved by using triflic acid catalyzed reaction with 2-hydroxy chloro sugar 6. Condensation of 7 with rhamnosyl chloride 8 was accomplished by our original thermal glycosylation procedure in very high α-selectivity. Hemiacetal 12 was coupled with 8 by means of AgOTf catalyzed Koenigs-Knorr type reaction. Trisaccharide 14, a possible structure of osladin, was derived from 12 in four steps. However the aqueous solution of 14 did not show any sweet taste at all. Thus we have to continue the investigation to find the real structure of osladin by means of synthetic as well as isolation study.
