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 additionRobinson 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