10.1021/ol800326n
The research article details the first total synthesis of (-)-achilleol B, a triterpene extracted from Achillea odorata, achieved through a convergent approach with a 14-step linear sequence. Key steps included an enantioselective Robinson annelation for bicyclic moiety construction, a Ti(III)-mediated cyclization of a chiral monoepoxide obtained via asymmetric dihydroxylation of geranylacetone, and the use of commercially available geranylacetone as a starting material. Reactants utilized in the synthesis encompassed chiral monoepoxides, geranylacetone, and various reagents for the cyclization and protection steps, such as Cp2TiCl2, Mn, TMSCl-collidine, PBr3, and umbelliferone. The synthesis also involved the preparation of synthons A and B, with A being derived from geranylacetone through a series of reactions including asymmetric dihydroxylation and Horner-Wadsworth-Emmons protocol, and B from an enantioselective Robinson annulation using 2S-phenylethylamine. Analyses included 1H and 13C NMR spectroscopy, mass spectrometry (MS), and optical rotation measurements to confirm the structure and absolute stereochemistry of the synthesized compounds, which were compared with those of the natural product to reassign the stereochemistry of achilleol B and establish its absolute stereochemistry.
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