Synthesis of Biotinylated Galiellalactone Analogues  

作　　者：Zilma Escobar Martin Johansson Anders Bjartell Rebecka Hellsten Olov Sterner 

机构地区：[1]Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Lund, Sweden [2]Division of Urological Cancers, Department of Clinical Sciences Malmö , Lund University, Malmö , Sweden

出　　处：《International Journal of Organic Chemistry》2014年第4期225-235,共11页有机化学国际期刊（英文）

摘　　要：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.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.

关 键 词：STAT3 Galiellalactone BIOTIN SYNTHESIS 

分 类 号：O6[理学—化学]