Synthetic studies on amipurimycin: total synthesis of a thymine nucleoside analogue.
Amipurimycin, a member of the complex peptidyl nucleoside family of antibiotics, is a Streptomyces-derived potent antifungal agent. The mechanism of action of amipurimycin, however, remains undetermined. Additionally, there are no reports on the total synthesis or structure-activity relationships (SAR) of this potentially useful bioactive compound. In a study aimed at the total synthesis and SAR studies of this natural product, the present research reports the development of a synthetic route to the central pyranosyl amino acid core of amipurimycin and its further elaboration, culminating in the synthesis of a unique thymine analogue. Utilizing a d-serine-derived dihydroaminopyrone as a strategic building block, the synthesis involves de novo construction of the fully functionalized C-3-branched carbohydrate amino acid core, followed by glycosidic attachment of thymine at C-1, and peptidic linking of the C-6 amine with the 1,2-aminocyclopentane carboxylic acid side chain.
Stauffer
Christina S
CS
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA.
Datta
Apurba
A
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013941:Thymine / Q000138:chemical synthesis* / Q000737:chemistry
D000935:Antifungal Agents; D011687:Purines; C013810:amipurimycin; D013941:Thymine