Ten members of the mezzettiaside family of natural products were synthesized and evaluated for anticancer and antibacterial activity. Complete anticancer (H460) and antibacterial ( B. subtilis ) activities for the ten natural products and four new analogues were found. Comparison to the cleistrioside and cleistetroside classes of natural products were made.

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The first synthesis of any and all members of the mezzettiaside family of natural products has been achieved. The reported synthesis features the iterative use of the Taylor catalyst in a dual nucleophilic boron/electrophilic palladium catalyzed regioselective glycosylation. In addition, the de novo approach utilizes atomless protecting groups and the minimal use of protecting groups (2 chloroacetates for the synthesis of 10 natural products). These divergent syntheses occurred in a range of 13 to 22 longest linear steps and required only 41 total steps to prepare the entire family of mezzettiasides.

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Activity-guided fractionation of a stem extract of Mezzettia leptopoda using human oral epidermoid carcinoma (KB) cells led to the isolation of seven highly acylated oligorhamnosides. Four of these constituents are novel, namely, n-octyl 2-O-acetyl-alpha-L-rhamnopyranosyl-(1-->3)-2, 4-di-O-acetyl-alpha-L-rhamnopyranosyl-(1-->3)-4-O-hexanoyl-alpha-L-rh amnopyranoside (mezzettiaside 8) (1); n-octyl 2, 3-di-O-acetyl-alpha-L-rhamnopyranosyl-(1-->3)-4-O-hexanoyl-alpha-L-rh amnopyranoside (mezzettiaside 9) (2); n-octyl 2, 4-di-O-acetyl-alpha-L-rhamnopyranosyl-(1-->3)-4-O-hexanoyl-alpha-L-rh amnopyranoside (mezzettiaside 10) (3); and n-octyl 2,3, 4-tri-O-acetyl-alpha-L-rhamnopyranosyl-(1-->3)-4-O-hexanoyl-alpha-L-r hamnopyranoside (mezzettiaside 11) (4). Three known compounds were identified as mezzettiasides 2 (5), 3 (6), and 4 (7), respectively, previously isolated from this same plant. The structures of novel compounds 1-4 were determined by spectroscopic methods. All the isolates were evaluated against a panel of human cancer cell lines in this study, and compounds 1-2 and 4-7 were found to be weakly cytotoxic toward KB and/or human colon and lung cancer cell lines.

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