• Chemoenzymatic Approach to Tetrodotoxin: Synthesis of Fukuyama’s, Alonso’s, and Sato’s Advanced Intermediates

      Baidilov, Daler; Rycek, Lukas; Trant, John F.; Froese, Jordan; Murphy, Brennan; Hudlicky, Tomas (Wiley, 2018-05-11)
      The advanced intermediates in the syntheses of tetrodotoxin reported by Fukuyama, Alonso, and Sato were prepared. The key steps in the synthesis of the title compounds involved the toluene dioxygenase–mediated dihydroxylation of either iodobenzene or benzyl acetate. The resulting diene diols were transformed to Fukuyama’s intermediate in six steps, to Alonso’s intermediate in nine steps and to Sato’s intermediate in ten steps, respectively.
    • Chemoenzymatic Synthesis of the Antifungal Compound(–)-Pestynol by a Convergent, Sonogashira Construction of the Central Yne-Diene

      Borra, Suresh; Kumar, Manoj; McNulty, James; Baidilov, Daler; Hudlicky, Tomas (Wiley, 2018-10-19)
      A total synthesis of the fungal-derived natural prod-uct pestynol is reported via a convergent chemoenzymatic ap-proach from the readily available precursors geranyl bromide,ethyl acetoacetate, trimethylsilylacetylene, and bromobenzene. Synthetic (–)-pestynol proved to be identical in all respects to thenatural material, allowing confirmation of the structure includ-ing absolute stereochemistry.
    • Isolation, Synthesis, and Semi-synthesis of Amaryllidaceae Constituents from Narcissus and Galanthus sp.: De novo Total Synthesis of 2-epi-Narciclasine.

      Borra, Suresh; Lapinskaite, Ringaile; Kempthorne, Christine; Liscombe, David; McNulty, James; Hudlicky, Tomas (ACS, 2018-05-22)
      An efficient protocol for the isolation of narciclasine from common Amaryllidaceae bulbs, separation from haemanthamine, and the occurrence of a trace alkaloid, 2-epi-narciclasine are reported. Attempts to convert natural narciclasine to its C-2 epimer by Mitsunobu inversion or oxidation/reduction sequences were compromised by rearrangement and aromatization processes, through which a synthesis of the alkaloid narciprimine was achieved. The methylation of the 7-hydroxy group of natural narciclasine followed by protection of the 3,4-diol function and oxidation/reduction sequence provided the target C-2 epimer. A de novo chemoenzymatic synthesis of 2-¬epi-narciclasine from m-dibromobenzene is also described. Haemanthamine and narciprimine were readily detected in the crude extracts of Narcissus and Galanthus bulbs containing narciclasine and the occurrence of 2-epi-narciclasine as a trace natural product in Galanthus sp. is reported for the first time.