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Efforts towards the first total synthesis of (-)-oxazolomycin B and (+)-oxazolomycin C from the intermediate of our previous synthesis of (+)-neoxazolomycin are reported. The syntheses were achieved in a longest linear sequence of 25 steps from the amino acid serine in 3.6 and 2.7 % overall yields, respectively. The efficiency of our approach is derived from silyl triflate-mediated reductive oxazolidine ring-opening and Fürstner's Ru-catalyzed hydrosilylation and protodesilylation reactions. The obtained spectra and optical rotations were in good agreement with those of natural products, thus confirming the structures.

A diverted total synthesis effort is described that is designed to prepare potent cytotoxins based on the actin-binding natural product bistramide A. The major focus of this study is the preparation of analogues that contain oxygenation at the C29 position, which is necessary for a key reaction in the sequence but is not present in the natural product. This process showed that C29 ketone analogues are accessed more readily and show similar potency compared to the natural product. The ability to incorporate C29 oxygenation and to replace a secondary alcohol by a primary alcohol allowed for the development of a more convergent approach that provides a potent analogue in just eight steps in its longest linear sequence.

The first total synthesis of houttuynoid B, a powerful antiviral flavonoid glycoside from the Chinese plant Houttuynia cordata, is described. In a key step, a Baker-Venkataraman rearrangement employing an already glycosylated substrate was used to efficiently set up the fully functionalized carbon skeleton. The required benzofuran building block was prepared through a domino Sonogashira coupling/5-endo-dig cyclization and converted into a stable 1-hydroxybenzotriazole-derived active ester prior to linking with a galactosylated hydroxyacetophenone unit. The elaborated synthesis requires only nine steps (11 % overall yield) along the longest linear sequence and paves the way for the preparation of structurally related compounds for further biological evaluation.

Based on the asymmetric copper-catalyzed 1,2-addition of Grignard reagents to ketones, (R,R,R)--tocopherol has been synthesized in 36% yield over 12 steps (longest linear sequence). The chiral center in the chroman ring was constructed with 73% ee by the 1,2-addition of a phytol-derived Grignard reagent to an -bromo enone prepared from 2,3-dimethylquinone.

The total synthesis and stereochemical assignment of gallinamide A, an antimalarial depsipeptide of cyanobacterial origin, is described. Synthesis of the four possible N-terminal diastereoisomers of gallinamide A (including the natural product symplostatin 4) was achieved using a divergent strategy from a common imide fragment. The natural product and corresponding diastereoisomers were synthesized in 30-33% overall yield in a longest linear sequence of 8 steps. Comparative NMR spectroscopic studies of the four synthetic diastereoisomers with the isolated natural product demonstrated that gallinamide A possesses a dimethylated L-isoleucyl residue at the N-terminus. As such, we have shown that gallinamide A is structurally and stereochemically identical to symplostatin 4. Gallinamide A and its N-terminal diastereoisomers were also shown to possess significant antimalarial activity with IC(50) values in the nanomolar range against the 3D7 strain of Plasmodium falciparum.

The preceding manuscript detailed our synthesis of the gambierol A-C and F-H ring precursors. Reported herein is a description of the coupling of the two precursors and the conversion of the coupled material into gambierol. Coupling of the subunits involved ester formation, enol ether RCM, and mixed thioketal formation and reduction. By employing this strategy we were able to bring highly advanced subunits into the coupling and, as a result, we were able to minimize the number of post-coupling transformations required to complete gambierol. At the completion of the synthesis, we generated 7.5 mg (1.5 % overall yield) of (-)-gambierol in 44 steps (longest linear sequence).