| In previous work, an ethanolic extract of P. pensylvanicum exhibited inhibition of protein kinase C activity. Guided by PKC inhibition assays, six novel phenylpropanoid glycosides (vanicosides A–F), and the known compound, hydropiperoside were isolated from P. pensylvanicum . The observed differences in protein kinase C inhibitory activities amoung of these vanicosides prompted the objective of this research—to develop a library of vanicoside homologues both semisynthetically from the natural compounds and synthetically from sucrose. With this library in hand, structure-activity relationships might be drawn upon biological analysis and derivatives with improved inhibitory activities might be elucidated.; To help determine selectivity in the reaction of the hydroxyl and phenolic moieties of the vanicosides, as well as provide homologues for further biological testing, a number of semisynthetic derivatives were prepared from vanicoside B (11), including perhydrovanicoside B (52), a 3 ′-desacetylvanicoside B (56), and 2′ ,3′,4,4′-tetra-O-acetylvanicoside B (61). Two synthetic vanicoside homologues were prepared from sucrose, 1,3,6,6′-tetra-cinnamoylsucrose (45) and 1,3,6,6′-tetra-O-[4-O-benzyl-coumaryl]sucrose (77), a precursor of vanicoside D (13). In the synthetic scheme, the appropriate 3-acylsucrose derivative was prepared via cobalt chloride chelation assisted acylation of sucrose, and selectively silylated at the primary hydroxyls with t-butyldimethylsilyl chloride. The remaining secondary hydroxyls were then protected as levulinates. Selective deprotection of the TBDMS ethers under acidic conditions regenerated the primary hydroxyl moieties, which were subsequently acylated with the appropriate phenylpropenoyl anhydride. Removal of the levulinates gave the tetraacyl vanicoside homologues. In this manner, synthesis of the tetracinnamoyl sucrose (45) was successfully completed. Synthesis of 77, the precursor to vanicoside D was also achieved, but deprotection of the benzyl protected phenolic groups, without concomitant C-acylation of the aromati rings, was unsuccessful. |
