Advances in the Asymmetric Synthesis of Bridged and Fused Bicyclic Acetals

Abstract

Fused and bridged bicyclic acetals are important structural motifs found in a diverse array of biologically active molecules. These conformationally rigid but stable structural segments are established within natural and unnatural compounds with biological importance. The structural and biological features of the molecules containing the fused and bridged ring systems have triggered a profound impact in the layout of newer synthetic methodologies and other designed entities. The interest in the development of efficient strategies to construct bicyclic scaffolds with fused and bridged bicyclic acetals in a stereocontrolled manner is substantial and challenging in the community of synthetic chemistry. The purpose of this review is to shed some light on the intriguing chemistry involved in the synthesis of conformationally constrained bridged and fused bicyclic acetals and its exploitation towards the synthesis of complex natural and unnatural molecules of biological and synthetic interest.

Direct Synthesis of Bicyclic Acetals via Visible Light Catalysis

“…Bicyclic acetals are prevalent structural motifs in natural products, pharmaceuticals, and agrochemicals ( Pirrung et al., 1989 ; Brady et al., 2004 ; Alonso et al., 2005 ; Henry and Townsend, 2005 ; Zhou and Corey, 2005 ; Baird et al., 2009 ; Sastraruji et al., 2010 ; Mori et al., 2015 ; Ghosh et al., 2017 ; Karimov et al., 2018 ; Pan et al., 2018 ; Lenci et al., 2019 ; Bera et al., 2018 ). Compared with other privileged pharmacophores, such as biaryls, bicyclic acetals possess rigorous conformational rigidity, low molecular weight, and a pair of endogenous hydrogen bonding acceptors ( King et al., 2004 ; Surleraux et al., 2005 ; Ghosh et al., 2009 , 2011 ).…”

Co-catalysis of rhodium/phosphoramidite catalyst and ZSM-35(10) for the tandem hydroformylation–acetalization of olefins

“…1 In addition to classical aldehydes and ketones, unsaturated compounds including double bonds, triple bonds and epoxides act as reactants in reactions with alcohols to provide acetals. 2 Among the developed methods, the hydroformylation–acetalization of olefins is a chain-growth and direct route for the synthesis of acetals that uses olefins as the starting materials. The one-pot synthesis procedure shows a high atom economy and simplifies the purification of aldehydes.…”

Base-induced isomerization of red uroleuconaphins revisited: characterization and absolute stereochemistry of the yellow aphid pigments uroleuconaphins A2 and B2

“…4 The yellow pigments, namely, uroleuconaphins A 2 (3) and B 2 (4), are the minor components of the aphid pigments and isomers of uroleuconaphins A 1 and B 1 , which typically share a fused and bridged acetal moiety. 5 However, the structural details and biological activities of these pigments have not been investigated because of their poor availability (Fig. 1).…”