Gold(I)-Catalyzed Reactions of -Glycals with Propargyl Esters toward C-1 Alkenyl Spirocyclopropyl Carbohydrates.

An atom-economic and diazo-free strategy for the construction of novel pseudo anomeric C-1 alkenyl spirocyclopropyl sugars is described. Leveraging the 1,2-migration pathway of propargyl esters under gold(I) catalysis, easily available -glycals undergo β-selective alkenylcarbenoid insertion in moderate to excellent yields. Preferential activation of propargyl moieties and concerted [2 + 1] insertion are both favored through ligand choice and electron enrichment of esters.

An Unexpected Lewis Acid-Catalyzed Cascade during the Synthesis of the DEF-Benzoxocin Ring System of Nogalamycin and Menogaril: Mechanistic Elucidation by Intermediate Trapping Experiments and Density Functional Theory Studies.

An unexpected Lewis acid-catalyzed carbohydrate rearrangement of a 1,5-bis-glycopyranoside to the product of a formal intramolecular -aryl glycosylation reaction is reported. Mechanistic studies based mainly on intermediate trapping experiments and density functional theory (DFT) calculations reveal a cascade process involving three transient (a)cyclic oxocarbenium cations, the breaking of three single C(sp)-O bonds, and the formation of three single bonds (i.e.

Expanding the scope of the successive ring expansion strategy for macrocycle and medium-sized ring synthesis: unreactive and reactive lactams.

New methods are described that expand the scope of the Successive Ring Expansion (SuRE) with respect to synthetically challenging lactams. A protocol has been developed for use with 'unreactive' lactams, enabling SuRE reactions to be performed on subsrates that fail under previously established conditions. Ring expansion is also demonstarted on 'reactive' lactams derived from iminosugars for the first time.

Diastereoselective access to ,-glycosyl amino acids iron-catalyzed, auxiliary-enabled MHAT coupling.

Access to ,-glycosyl amino acids as a novel class of glycomimetics is reported by means of radical generation, intermolecular addition and stereoselective reduction a metal-induced hydrogen atom transfer (MHAT) sequence. The 'matched' coupling of -D-glycals with an enantiopure dehydroalanine bearing a ()-configured benzyl oxazolidinone enables a singular case of two-fold diastereocontrol under iron catalysis. In the common -D-glucal series, the nature of the C-2 substituent was found to play a key role from both reactivity and stereocontrol aspects.

Deconstructing Best-in-Class Neoglycoclusters as a Tool for Dissecting Key Multivalent Processes in Glycosidase Inhibition.

Multivalency represents an appealing option to modulate selectivity in enzyme inhibition and transform moderate glycosidase inhibitors into highly potent ones. The rational design of multivalent inhibitors is however challenging because global affinity enhancement relies on several interconnected local mechanistic events, whose relative impact is unknown. So far, the largest multivalent effects ever reported for a non-polymeric glycosidase inhibitor have been obtained with cyclopeptoid-based inhibitors of Jack bean α-mannosidase (JBα-man).