TITLE:
Synthesis of Biotinylated Galiellalactone Analogues
AUTHORS:
Zilma Escobar, Martin Johansson, Anders Bjartell, Rebecka Hellsten, Olov Sterner
KEYWORDS:
STAT3, Galiellalactone, Biotin, Synthesis
JOURNAL NAME:
International Journal of Organic Chemistry,
Vol.4 No.4,
November
18,
2014
ABSTRACT: 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.