Divergent Synthesis of Mogrosides

A general synthesis of mogrosides, the main active constituents of the intensely sweet ripe fruit of the plant <i>Siraitia grosvenorii</i> (Swingle) C. Jeffrey, commonly known as Monk fruit or Luo Han Guo, has been developed from the readily available aglycone mogrol. The key features of the synthesis include differentiation of the mogrol's 24-OH and 25-OH groups employing a 24,25-<i>O</i>-benzylidene acetal reductive ring-opening/silica gel-catalyzed 25-OAc→24-OH acetyl group migration sequence, differentiation of the 3-OH and 11-OH groups by selective deprotection, and glycosylation of the orthogonally protected mogrol derivatives at 3-OH and 24-OH, as well as protecting groups-directed installation of the branched 24-<i>O</i>-carbohydrate residues employing <i>N</i>-phenyltrifluoroacetimidate donors. Using this strategy, naturally occurring mogrosides IIE, III, and IIIE, siamenoside I, and three novel non-natural α-L-rhamnose-containing analogues of siamenoside I were conveniently synthesized. This diversity-oriented synthesis significantly improves accessibility to the whole family of mogrosides and non-natural analogues for biological studies.