We synthesized several sulfur isosters of ferulenol and related prenylcoumarins from Ferula communis preliminary to finding whether the antitubercular activity of these natural compounds might be dissociated from their antithrombin activity. Direct thionation of ferprenine, an instance of “diversity-oriented” synthesis, yielded a mixture of three thiocoumarin derivatives. When 4-hydroxy-2-deoxy-2-thiocoumarin was reacted with farnesal and other α,β-unsaturated aldehydes, the isosteric oxygen-sulfur substitution at position 2 surprisingly caused a regiochemical inversion in the tandem Knoevenagel-electrocyclic reaction, prevalently affording the linear adduct. An extensive investigation with variously substituted enals highlighted a competition between Knoevenagel and Michael addition. This result was rationalized by energy calculations that took into consideration steric and electronic factors as well as complex formation with the catalyst

Cyclization reactions of coumarin derivatives: Chemo- and regioselectivity effects of oxygen/sulfur isosteric replacement / G. Palmisano, L. Toma, R. Annunziata, S. Tagliapietra, A. Barge, G. Cravotto. - In: JOURNAL OF HETEROCYCLIC CHEMISTRY. - ISSN 0022-152X. - 2007:44(2007 Mar 30), pp. 411-418. [10.1002/jhet.5570440221]

Cyclization reactions of coumarin derivatives: Chemo- and regioselectivity effects of oxygen/sulfur isosteric replacement

R. Annunziata;
2007

Abstract

We synthesized several sulfur isosters of ferulenol and related prenylcoumarins from Ferula communis preliminary to finding whether the antitubercular activity of these natural compounds might be dissociated from their antithrombin activity. Direct thionation of ferprenine, an instance of “diversity-oriented” synthesis, yielded a mixture of three thiocoumarin derivatives. When 4-hydroxy-2-deoxy-2-thiocoumarin was reacted with farnesal and other α,β-unsaturated aldehydes, the isosteric oxygen-sulfur substitution at position 2 surprisingly caused a regiochemical inversion in the tandem Knoevenagel-electrocyclic reaction, prevalently affording the linear adduct. An extensive investigation with variously substituted enals highlighted a competition between Knoevenagel and Michael addition. This result was rationalized by energy calculations that took into consideration steric and electronic factors as well as complex formation with the catalyst
Cyclization Reactions ; Coumarin Derivatives
Settore CHIM/06 - Chimica Organica
30-mar-2007
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/28795
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 3
social impact