Stereoselective Synthesis of 1,2‐Annulated Sugars Having Substituted Tetrahydropyran/(‐furan) Scaffolds Using the Prins‐Reaction

Abstract

Lewis acid catalyzed silyl‐Prins/alkyne‐Prins reactions are utilized for the stereoselective synthesis of 1,2‐annulated sugars having substituted tetrahydropyran (or tetrahydrofuran) scaffolds from appropriately substituted sugar derived alkenyl (or alkynyl) alcohols. These annulated molecules having stereochemical/substitution dispositions similar to those of marine toxins such as maitotoxin could act as useful building blocks for the synthesis of these natural products. Further, the utility of the silyl‐Prins reaction is extended to the synthesis of cis‐sugar fused 4H‐naptho[1,2‐b]pyran and cis‐sugar fused pyrano[3,2‐c][1]benzopyran derivatives.

Synthesis of (5,6 & 6,6)-oxa-oxa annulated sugars as glycosidase inhibitors from 2-formyl galactal using iodocyclization as a key step

“…A few examples [25][26][27][28] include synthesis of sugar-fused furan derivative 6, 1,2-annulated 1,3oxazine 7, sugar-fused chroman 8 and furofuryl glycal 9 as shown in Figure 2. In addition to this, our group also has been actively involved in synthesis of several 1,2-annulated sugar molecules [29][30][31][32][33][34][35][36] which exhibit interesting glycosidase inhibitory behavior. These include sugar-pyrrolidine hybrid 10, 29 sugar morpholinone fused molecule 11 30 and sugar-piperidine hybrids 12 31 and 13 32 as shown in Figure 2.…”

New Avenues for the Synthesis of Oxa‐Cycles Using Lewis/Brønsted Acid Mediated Carboxygenation and Carboalkoxylation of Alkynes

“…[33] Along similar lines, Vankar et al have reported a chiral pool approach for the synthesis of sugar-fused THF moieties using carboxygenation of alkyne through alkyne Prins cyclization (Scheme 3). [34] The reaction of various sugar-fused alkynols 5 with aldehydes 6 in the presence of TMSOTf gave corresponding sugar-fused THFs 7 in good yield and diastereoselectivities.…”

Copper-catalyzed S-arylation of Furanose-Fused Oxazolidine-2-thiones

“…Amongst the various reported methods, the most common have used 1,2-annulation strategies such as metal-catalyzed reactions, Michael addition reactions, cycloaddition methods, radical-mediated reactions, or nucleophilic attacks [ 1 ]. For example, the formation of 1,2-annulated sugars, having substituted tetrahydropyran and tetrahydrofuran moieties, was investigated via Lewis acid-catalyzed silyl-Prins/alkyne-Prins reactions from appropriately substituted sugar alcohols [ 5 ]. Recently, a simple Pd(OAc) 2 -catalyzed strategy was presented using glucose and galactose for the synthesis of sugar-fused indolines via C-H activation/cyclization using the oxalyl group as an auxiliary protecting group [ 6 ].…”