Synthetic Studies Directed toward the Assembly of the C-Glycoside Fragment of the Telomerase Inhibitor D8646-2-6

Abstract

[reaction: see text] Construction and characterization of the C-glycosidic moiety of telomerase inhibitor D8646-2-6 (1) are described. This is the first example of the C-glycosylation using electron-poor aromatics, 4-hydroxypyrone, as a glycosyl acceptor. The glycosylation reaction and base-promoted isomerization affords desired beta-C-glycoside in a 61% overall yield.

2-Pyrone natural products and mimetics: isolation, characterisation and biological activity

“…30 Initial studies towards its total synthesis include the construction and characterisation of the C-glycosidic moiety. 31 The absolute stereochemistry of 12 is not known. 4-Hydroxy-2-pyrone derivatives can be formed after early termination, via two condensation reactions, of the valerophenone synthase (VPS) catalysed synthesis of the bitter acids in hops (Humulus lupulus).…”

Substrate Profile Analysis and ACP‐Mediated Acyl Transfer in Streptomyces coelicolor Type III Polyketide Synthases

“…Pyrones are synthesized by PKSs through successive condensations of malonyl-CoA derived C 2 units followed by lactonization. The fungal metabolites fusapyrone [8] and D8646-2-6 [9] are most likely derived from iterative type I PKSs, and enterocin [10] is produced by a type II PKS. On the other hand, germicidins A, B, and C, [11] as well as the signaling molecule precursor, phlorocaprophenone, [12] have been shown to be produced by PKS proteins from the type III family.…”

N‐Heterocyclic Carbene‐Catalyzed Annulation of Ylides with Ynals: Direct Access to α‐Pyrones

“…α‐Pyones are frequently observed as the core in numerous natural products and biologically important molecules (Figure ) . They have exhibited promising biological activities, such as anti‐HIV, antimicrobial, antifungal, telomerase inhibition, pheromonal, androgen, cardiotonic, neurotoxic and phytotoxic effects . In medicinal chemistry, α‐pyones often serve as convenient precursors for the assembly of other medicinal important structures .…”