10.1021/jo801956w.s001 Min Yu Min Yu Susan S. Pochapsky Susan S. Pochapsky Barry B. Snider Barry B. Snider Synthesis of 7-Epineoptilocaulin, Mirabilin B, and Isoptilocaulin. A Unified Biosynthetic Proposal for the Ptilocaulin and Batzelladine Alkaloids. Synthesis and Structure Revision of Netamines E and G American Chemical Society 2008 Synthesi guanidine intramolecular Michael reaction netamine E isoptilocaulin side chains trans MnO 2 oxidation dehydroptilocaulin oxidation state tricyclic epineoptilocaulin Unified Biosynthetic Proposal enone Hydride 2008-11-21 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Synthesis_of_7_Epineoptilocaulin_Mirabilin_B_and_Isoptilocaulin_A_Unified_Biosynthetic_Proposal_for_the_Ptilocaulin_and_Batzelladine_Alkaloids_Synthesis_and_Structure_Revision_of_Netamines_E_and_G/2898385 Addition of guanidine to a 6-methylhexahydroindenone in MeOH at 85 °C afforded 7-epineoptilocaulin. A similar reaction with a 6-propylhexahydroindenone afforded netamine E. MnO<sub>2</sub> oxidation of 7-epineoptilocaulin and netamine E afforded mirabilin B and netamine G, respectively. The netamines have the side chains trans, not cis as was initially proposed. A unified biosynthetic scheme for the batzelladines and ptilocaulin family is proposed. Conjugate addition of guanidine to a bis enone followed by an intramolecular Michael reaction of the enolate to the other enone, aldol reaction, dehydration, and enamine formation will lead to a tricyclic intermediate at the dehydroptilocaulin oxidation state. 1,4-Hydride addition will lead to ptilocaulin or 7-epineoptilocaulin depending on which face the hydride adds to. 1,2-Hydride addition will lead to isoptilocaulin. The key tricyclic intermediate was prepared from a tetrahydroindenone and guanidine and reduced with NaBH<sub>4</sub> to give a mixture rich in ptilocaulin and isoptilocaulin.