An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

Abstract

An efficient, eco-compatible diversity-oriented synthesis (DOS) approach for the generation of library of sugar embedded macrocyclic compounds with various ring size containing 1,2,3-triazole has been developed. This concise strategy involves the iterative use of readily available sugar-derived alkyne/azide-alkene building blocks coupled through copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction followed by pairing of the linear cyclo-adduct using greener reaction conditions. The eco-compatibility, mild reaction conditions, greener solvents, easy purification and avoidance of hazards and toxic solvents are advantages of this protocol to access this important structural class. The diversity of the macrocycles synthesized (in total we have synthesized 13 macrocycles) using a set of standard reaction protocols demonstrate the potential of the new eco-compatible approach for the macrocyclic library generation.

Keywords: carbohydrate; click chemistry; diversity-oriented synthesis; macrocycles; ring-closing metathesis.

Figure 1

Build-couple-pair (B/C/P) strategy for macrocycles.

Figure 2

Different building blocks used for DOS.

Scheme 1

Cycloaddition reaction of alkyne-azide building block.

Scheme 2

Acetylation of macrocycle 4m.