Divergent Synthesis of Mogrosides

A general synthesis of mogrosides, the main active constituents of the intensely sweet ripe fruit of the plant Siraitia grosvenorii (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-O-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-O-carbohydrate residues employing N-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.