title: Direct Mitsunobu monoesterification of N-protected tobramycin competes with intramolecular pyrrolidine formation in ester prodrug synthesis.
abstract: Unlike the related aminoglycoside neomycin B, N-protected tobramycin can be selectively esterified at its sole, primary hydroxyl group under Mitsunobu conditions. However, depending on the reaction conditions, the reaction can take a different course with intramolecular cyclization of an N-Boc amine leading to formation of an unusual tobramycin pyrrolidine derivative as the major reaction product.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia.
authors.forename: Sabina
authors.initials: S
authors.lastname: Quader
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia.
authors.forename: Sue E
authors.initials: SE
authors.lastname: Boyd
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Jenkins
authors.affiliation: Institute for Glycomics and School of Natural Sciences, Griffith University, Gold Coast, QLD 4222, Australia. Electronic address: t.houston@griffith.edu.au.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Houston
mesh_terms: D001667:Binding, Competitive; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D004951:Esterification; D004952:Esters; D009584:Nitrogen / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D014031:Tobramycin / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D004952:Esters; D011355:Prodrugs; D011759:Pyrrolidines; C032519:pyrrolidine; D009584:Nitrogen; D014031:Tobramycin
keywords: Aminoglycosides; Antitubercular compounds; Drug delivery; Esterification