Total synthesis of potent antifungal marine bisoxazole natural products bengazoles A and B.
The bengazoles are a family of marine natural products that display potent antifungal activity and a unique structure, containing two oxazole rings flanking a single carbon atom. Total syntheses of bengazole A and B are described, which contain a sensitive stereogenic centre at this position between the two oxazoles. Additionally, the synthesis of 10-epi-bengazole A is reported. Two parallel synthetic routes were investigated, relying on construction of the 2,4-disubstituted oxazole under mild conditions and a diastereoselective 1,3-dipolar cycloaddition. Our successful route is high yielding, provides rapid access to single stereoisomers of the complex natural products and allows the synthesis of analogues for biological evaluation.
Bull
James A
JA
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Balskus
Emily P
EP
Horan
Richard A J
RA
Langner
Martin
M
Ley
Steven V
SV
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001330:Electronic Data Processing; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D000935:Antifungal Agents; D010080:Oxazoles; C519397:bengazole A