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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

✍ Scribed by Antonio Guerriero; Michele D'Ambrosio; Giuseppe Chiasera; Francesco Pietra


Publisher
John Wiley and Sons
Year
1994
Tongue
German
Weight
546 KB
Volume
77
Category
Article
ISSN
0018-019X

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✦ Synopsis


Dedicated to the memory of Mario Pieti-a

(5. VII.94) The absolute configuration of agelastatin A (I), the major, strongly cytotoxic alkaloid of the axinellid sponge Agelas dendromorpha from the Coral Sea, is proposed here to be (5aS,5bS,8aS,9aR), 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. o e