Amipurimycin: Total Synthesis of the Proposed Structures and Diastereoisomers

Abstract

The proposed diastereoisomers (1a-d)together with their C8'-epimers (1e-h)ofamipurimycin, aunique antifungal peptidyl nucleoside antibiotic,h ave been synthesized for the first time.T he synthetic approach is efficient and stereodivergent, and features as tereoselective aldol condensation to build the branched C9 sugar amino acid skeleton and aregioand stereocontrolled gold(I)-catalyzed N-glycosylation to furnish the purine nucleoside.A nalysis of the NMR data suggests that the previously assigned configuration of the tertiary C3' in amipurimycin should be of opposite configuration.

The Amipurimycin and Miharamycin Biosynthetic Gene Clusters: Unraveling the Origins of 2-Aminopurinyl Peptidyl Nucleoside Antibiotics

“…Cispentacin Biosynthesis Mirrors Biosynthesis of Coronafacic Acid. The introduction of (−)-cispentacin (16) to the saccharide core is a key tailoring step in amipurimycin biosynthesis. The construction of (−)-cispentacin is presently obscure despite its importance as a lead compound in the development of icofungipen, a potent antifungal compound that inhibits eukaryotic leucyl-tRNA synthetase.…”

“…The biosynthetic gene clusters and pathways for amipurimycin and the miharamycins have not been reported to date. Interestingly, while the total synthesis of amipurimycin was accomplished only recently, 16 some 40 years after the initial discovery of this PNA, a successful total synthesis of a miharamycin has yet to be reported. 17,18 Herein, we identify and characterize the biosynthetic gene clusters of the miharamycins and amipurimycin from S. miharaensis and S. novoguineensis, respectively.…”

Study of the N7 Regioselective Glycosylation of 6-Chloropurine and 2,6-Dichloropurine with Tin and Titanium Tetrachloride

“…Various methodologies have been described in known monographs and recent reviews. 21−25 Recently described effective methodologies also include Nglycosylation of purines mediated by hypervalent iodine, 26 goldcatalyzed purine glycosylation, 27 the Mitsunobu reaction, 28 or a reaction promoted by the (p-Tol) 2 SO/Tf 2 O catalyst. 21 These reactions provide predominantly N 9 -nucleosides as major products in purine chemistry.…”