A Highly Stereoselective Total Synthesis of Hispidospermidin:  Derivation of a Pharmacophore Model Alison J. Frontier Subharekha Raghavan Samuel J. Danishefsky 10.1021/ja9944960.s001 https://acs.figshare.com/articles/journal_contribution/A_Highly_Stereoselective_Total_Synthesis_of_Hispidospermidin_Derivation_of_a_Pharmacophore_Model/3678921 The total synthesis of the title compound has been accomplished. Among the key steps were (i) a conjugate additionRobinson annulation-type sequence (see <b>4</b>), (ii) intramolecular carbomercuration (see <b>3</b>), (iii) a reduction−ketonization sequence (see <b>25</b>), (iv) cycloetherification of an unactivated methylene group (see <b>28</b>), and reductive amination (see <b>1</b>). A highly preliminary SAR profile suggests that the functional cytotoxic pharmacophore of hispidospermidin involved a presentation of spermidine derivative <b>36</b> via linkage to a ball-like hydrophobic cage to its target. 2000-06-13 00:00:00 sequence ii conjugate reductive amination Pharmacophore Model cage cycloetherification intramolecular carbomercuration presentation synthesis Hispidospermidin title compound Derivation hispidospermidin iii linkage unactivated methylene group Stereoselective spermidine cytotoxic pharmacophore SAR profile Synthesi