Author(s)

Zilma Escobar¹, Martin Johansson², Anders Bjartell², Rebecka Hellsten², Olov Sterner^1*

¹Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Lund, Sweden.
²Division of Urological Cancers, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.

Two biotinylated derivatives of the fungal metabolite galiellalactone (1) were synthesized in order to facilitate the investigation of the molecular mechanism of action of the galiellalactonoids. Galiellalactone is a STAT3-signaling inhibitor that inhibits growth in vitro as well as in vivo of prostate cancer cells expressing activated STAT3. To provide a suitable point of attachment for biotin, the 8-hydroxymethyl derivative (3) and its 7-phenyl analogue 4 were synthesized by a modified tandem Pd-catalysed carbonylation and intramolecular vinyl allene Diels-Alder procedure previously developed. The two primary alcohols obtained, 3 and 4, were coupled to biotin as the 6-aminohexanoic acid amide, activated as the acid chloride, yielding the derivatives 5 and 6.

STAT3, Galiellalactone, Biotin, Synthesis

Escobar, Z. , Johansson, M. , Bjartell, A. , Hellsten, R. and Sterner, O. (2014) Synthesis of Biotinylated Galiellalactone Analogues. International Journal of Organic Chemistry, 4, 225-235. doi: 10.4236/ijoc.2014.44026.