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The Thia‐Michael Reactivity of Zerumbone and Related Cross‐Conjugated Dienones: Disentangling Stoichiometry, Regiochemistry, and Addition Mode with an NMR‐Spectroscopy‐Based Cysteamine Assay
Author(s) -
Appendino Giovanni,
Minassi Alberto,
Collado Juan A.,
Pollastro Federica,
Chianese Giuseppina,
TaglialatelaScafati Orazio,
Ayyari Mehdi,
Garcia Victor,
Muñoz Eduardo
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201500237
Subject(s) - chemistry , isomerization , michael reaction , reactivity (psychology) , conjugated system , cyanine , nuclear magnetic resonance spectroscopy , covalent bond , photochemistry , thiol , cysteamine , stereochemistry , organic chemistry , fluorescence , polymer , alternative medicine , physics , pathology , quantum mechanics , catalysis , medicine
The cross‐conjugated and electrophilic dienone system of the humulane sesquiterpene zerumbone ( 1a ) was modified by E / Z photochemical isomerization and/or by removal of homoconjugation with the isolated endocyclic double bond of the medium‐sized ring. The site (C‐6/C‐9), mode (transient or irreversible), stoichiometry (single or twofold), and comparative rates of thiol addition were evaluated using an NMR‐spectroscopy‐based cysteamine assay. Dramatic effects were seen, and this highlights the subtleties of the reaction and the limitations of our predictive power in this field. For biological endpoints sensitive to thiol trapping, a substantial separation between Michael reactivity and biological activity was found for 1a and its analogues. This supports the view that shape complementarity plays a critical role in the covalent binding of Michael acceptors to their macromolecular target(s).