Total synthesis and antifungal activity of a carbohydrate ring-expanded pyranosyl nucleoside analogue of nikkomycin B.
In a study aimed at investigating an as yet unknown structure-activity relationship of the nikkomycin family of antifungal peptidyl nucleoside antibiotics, the present research reports the synthesis and antifungal evaluation of a carbohydrate ring-expanded pyranosyl nucleoside analogue of nikkomycin B. Employing a convergent synthetic route, independent synthesis of the N-terminal amino acid side chain and a stereoselective de novo construction of the desired pyranosyl nucleoside amino acid fragment was followed by peptidic coupling of the two components, leading to the first synthesis of a carbohydrate ring-enlarged pyranosyl nikkomycin B analogue. In vitro biological evaluation of the above analogue against a variety of human pathogenic fungi demonstrated significant antifungal activity against several fungal strains of clinical significance.
Stauffer
Christina S
CS
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045-2500, USA.
Bhaket
Pushpal
P
Fothergill
Annette W
AW
Rinaldi
Michael G
MG
Datta
Apurba
A
D000617:Aminoglycosides / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D003904:Mitosporic Fungi / Q000187:drug effects*; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000935:Antifungal Agents; D002241:Carbohydrates; D004151:Dipeptides; D009705:Nucleosides; C527460:nikkomycin B; C527461:pyranosyl nikkomycin B; C011952:nikkomycin