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A Highly Stereoselective Total Synthesis of Hispidospermidin: Derivation of a Pharmacophore Model
journal contribution
posted on 2000-06-13, 00:00 authored by Alison J. Frontier, Subharekha Raghavan, Samuel J. DanishefskyThe total synthesis of the title compound has been accomplished. Among the key steps were (i) a
conjugate additionRobinson annulation-type sequence (see 4), (ii) intramolecular carbomercuration (see 3),
(iii) a reduction−ketonization sequence (see 25), (iv) cycloetherification of an unactivated methylene group
(see 28), and reductive amination (see 1). A highly preliminary SAR profile suggests that the functional cytotoxic
pharmacophore of hispidospermidin involved a presentation of spermidine derivative 36 via linkage to a ball-like hydrophobic cage to its target.