A Hexavalent Basket for Bottom-Up Construction of Functional Soft Materials and Polyvalent Drugs through a "Click"...

Inspired by polyvalency and its prevalence in nature, we developed an efficient synthetic route for accessing a large variety of multivalent and dual-cavity baskets from inexpensive and abundant starting materials. First, the cycloaddition of vinyl acetate to anthracene was optimized to, upon hydrolysis, give dibenzobarrelene derivative 6, which after five functional group transformations and then cyclotrimerization gave heptiptycene dodecaester 4 in an overall 17 % yield. Following that, compound 4 was converted into D_3h symmetric 1, composed of two fused cavitands each holding three terminal alkynes at the rim for conjugation to functional molecules using the highly efficient CuAAC reaction. To survey the reactivity of hexavalent 1, we "clicked" 2-acetamido-2-deoxy-β-d-glucopyranosyl azide 3,4,6-triacetate (carbohydrate), methoxypolyethylene glycol azide (PEG, M_n =2000; polymer) and benzyl azide (aromatic) to obtain hexavalent conjugates 12-14 in 50-79 % yields. In summary, dual-cavity 1 is an accessible, structurally-unique and hexavalent host that can be "clicked" to a variety of functional molecules for (a) combinatorial lead identification of drugs, (b) preparation of hierarchical soft materials and (c) design of selective chemosensors, scavengers, or supramolecular catalysts.