Synthetic studies on ezomycins: stereoselective route to a thymine octosyl nucleoside derivative.
The ezomycins are Streptomyces-derived antifungal natural products, belonging to the complex peptidyl nucleoside family of antibiotics. Employing D-serine as a chiral platform, we report herein a novel synthetic route to the bicyclic octosyl nucleoside core of the ezomycins. A key step in the sequence involved a stereoselective 6-exo-trig oxymercurationoxidation of a strategic delta-hydroxy alkene derivative, toward construction of the trans-fused furopyran ring system as present in the target products. In contrast to the known carbohydrate-based synthetic routes to the above furopyranyl fragment, the present amino acid chiral template approach is expected to offer a more flexible pathway toward potential SAR-targeted structural/stereochemical modifications of this central bicyclic nucleoside component of the ezomycins.
Khalaf
Juhienah K
JK
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, USA.
VanderVelde
David G
DG
Datta
Apurba
A
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D013237:Stereoisomerism; D013941:Thymine / Q000737:chemistry*
D000617:Aminoglycosides; D009705:Nucleosides; C039957:ezomycin; D013941:Thymine