Papulacandin D

Advances in the Pd-catalyzed synthesis of C-glycosides and branched sugars are summarized herein and the strategies are categorized based on named reactions or types of sugar moieties involved in the reactions. These include cross-coupling reactions, C-H activations, and carbonylative cross-coupling reactions. Applications of Pd-catalyzed C-glycosylation reactions are discussed in the synthesis of natural products and biologically active molecules such as bergenin, papulacandin D, and SGLT2-inhibitors. Important mechanistic cycles are drawn and the mechanisms for how Pd-activates the sugar moieties for various coupling partners are discussed. The directing group-assisted C-glycosylation and some intramolecular C-H activation reactions are also included.

Secondary metabolites of microorganisms have proven to be an excellent source of drugs. We isolated a new antibiotic, named pestiocandin (1), from a culture broth of a filamentous fungus, Pestalotiopsis humus FKI-7473, using a multidrug-sensitive budding yeast, S. cerevisiae 12geneΔ0HSR-iERG6. The structure of 1 was elucidated by various NMR studies. All geometric isomerisms of 1 were shown to be the E-form and two pyranose units of 1 were found to be glucose and galactose types. Compound 1 showed weak growth inhibition against Gram-positive and Gram-negative bacteria, yeasts and a filamentous fungus. It displayed more potent growth inhibition against multidrug-sensitive yeasts than wild-type yeasts.

A systematic study of the addition of C-based nucleophiles to fluorinated lactones based on 2-deoxy-2-fluoro-d-pyranoses is disclosed. This high yielding, α-selective process was found to be independent on the nature or configuration [(R)-C(sp3)-F, (S)-C(sp3)-F] of the substituent at C2. Representative, fluorinated analogues of Trehalose, Carminic acid, and the spirocyclic cores of Tofogliflozin and Papulacandin D are also reported. These glycomimics constitute a valuable series of 19F NMR active probes for application in structural biology.