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Synthesis and First Biological Evaluation of an Iron‐Containing HETE Analogue
Author(s) -
KauschBusies Nina,
Kater Benjamin,
Neudörfl Jörg M.,
Prokop Aram,
Schmalz HansGünther
Publication year - 2011
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.201001445
Subject(s) - chemistry , synthon , hexafluorophosphate , substituent , stereochemistry , aldehyde , moiety , cationic polymerization , context (archaeology) , metal , medicinal chemistry , organic chemistry , paleontology , ionic liquid , biology , catalysis
As previous studies in the field of bioorganometallic chemistry have unveiled, metal‐containing analogues of natural products frequently exhibit surprising biological activities. In this context, a synthetic approach to analogues of the eicosanoids 5‐HETE and 8‐HETE possessing a 1,3‐butadiene–Fe(CO) 3 substructure was elaborated. The chosen structures are characterized by a central (2 E ,4 Z )‐hexa‐2,4‐dien‐1‐ol–Fe(CO) 3 moiety (as the potential “metal pharmacophore”) and carry a lipophilic ω‐6‐substituent as well as a hydrophilic α‐side chain (carboxylic acid). Using the cationic complex tricarbonyl[η 5 ‐1‐(methoxycarbonyl)pentadienyl]iron hexafluorophosphate ( rac ‐ 4 ) as a starting material, the synthesis of a simplified Fe(CO) 3 ‐complexed HETE analogue ( rac ‐ 3 ) was achieved by exploiting the addition of an alkynyl Cu species to rac ‐ 4 . The carbon skeleton was completed through diastereo(Ψ‐ exo )selective addition of a titanium–zinc organyl [prepared from ethyl 4‐iodobutyrate, activated Zn powder, and Ti(O i Pr) 3 Cl] as a butyrate D 4 synthon to an aldehyde function by using 2‐Me‐THF as the solvent of choice. The (sensitive) target compound rac ‐ 3 was shown to induce apoptosis at moderate concentrations in cancer cells (BJAB and Nalm‐6).