Synthesis of Ophiocerins from Non-Carbohydrate Sources

Direct and unified synthetic routes to ophiocerin A, B, C, and D have been successfully developed. These syntheses are based on ring-closing metathesis and non-carbohydrate starting materials and are simpler and more efficient than the previous syntheses, as demonstrated in the case of ophiocerin B (2) (eleven steps from methyl α-D-glucopyranoside vs. four steps from 4-penten-2-ol) and ophiocerin A (1) (twelve steps from methyl α-D-glucopyranoside vs. three steps from 4-penten-2-ol). These routes will be useful for the practical synthesis of related natural products. Ophiocerins are comprised of four compounds isolated from the aqueous fungi Ophioceras venezuelense, each bearing a tetrahydropyran ring with an interesting array of substituents (Figure 1). Since substituted tetrahydropyran rings are found in many biologically important natural products, ophiocerins have attracted the attention of synthetic chemists