Divergent syntheses of resorcylic acid lactones: L-783277, LL-Z1640-2, and hypothemycin.
The resorcylic acid lactones (RAL) are endowed with diverse biological activity ranging from transcription factor modulators (zearalenone and zearalenol) to HSP90 inhibitors (radicicol and pochonin D) and reversible (aigialomycin D) as well as irreversible kinase inhibitors (hypothemycin and other RAL containing a cis-enone). Our interest in broadening the diversity of this family beyond naturally occurring diversity has led us to seek a general approach that could be used to address the entire spectrum of functionalities present within this family. Herein, we present our efforts on accessing macrocycles bearing an alkane, alkene, or epoxide at the benzylic position from a common benzylic sulfide intermediate to access L-783277, LL-Z1640-2, and hypothemycin.
Dakas
Pierre-Yves
PY
Institut de Science et Ingénierie Supramoléculaires (ISIS-UMR 7006), Université de Strasbourg-CNRS, 8 allée Gaspard Monge, 67000 Strasbourg, France.
Jogireddy
Rajamalleswaramma
R
Valot
Gaëlle
G
Barluenga
Sofia
S
Winssinger
Nicolas
N
D000478:Alkylation; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D062385:Hydroxybenzoates / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D012118:Resorcinols / Q000138:chemical synthesis* / Q000737:chemistry; D012451:Safrole / Q000031:analogs & derivatives / Q000737:chemistry; D013237:Stereoisomerism; D013440:Sulfides / Q000737:chemistry; D015025:Zearalenone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry
D018841:HSP90 Heat-Shock Proteins; D062385:Hydroxybenzoates; C405053:L 783277; C118715:LL Z1640-2; D007783:Lactones; D047428:Protein Kinase Inhibitors; D012118:Resorcinols; D013440:Sulfides; C120440:hypothemycin; D015025:Zearalenone; D012451:Safrole; C005746:sulfoxide