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Conformational Preferences and Absolute Configuration of Agelastatin A, a Cytotoxic Alkaloid of the Axinellid Sponge Agelas dendromorpha from the Coral Sea, via combined molecular modelling, NMR, and exciton splitting for diamide and hydroxyamide derivatives
Author(s) -
Guerriero Antonio,
D'Ambrosio Michele,
Chiasera Giuseppe,
Pietra Francesco
Publication year - 1994
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19940770720
Subject(s) - chemistry , sponge , alkaloid , coral , absolute configuration , stereochemistry , two dimensional nuclear magnetic resonance spectroscopy , oceanography , botany , biology , geology
The absolute configuration of agelastatin A ( 1 ), the major, strongly cytotoxic alkaloid of the axinellid sponge Agelas dendromorpha from the Coral Sea, is proposed here to be (5a S ,5b S ,8a S ,9a R ), as deduced from combined molecular‐mechanics calculations and a novel application of exciton splitting to the bis[4‐(dimethylamino)benzoyl] compounds (–)‐ 9 and (–)‐ 13 , derivatives of a diamide and a hydroxyamide, respectively. The position of the conformational equilibrium of A 1 could be finely tuned by slight molecular changes. The minor analogue, agelastatin B ( 3 ), was isolated as the trimethyl derivative (–)‐ 4 .