Abstract
Glycomacrolactones exhibit many interesting biological properties, and they are also important in molecular recognitions and for supramolecular chemistry. Therefore, it is important to be able to access glycomacrocycles with different sizes and functionality. A new series of carbohydrate-based macrocycles containing triazole and lactone moieties have been designed and synthesized. The synthesis features an intramolecular nucleophilic substitution reaction for the macrocyclization step. In this article, the effect of some common sulfonate leaving groups is evaluated for macrolactonization. Using tosylate gave good selectivity for monolactonization products with good yields. Fourteen different macrocycles have been synthesized and characterized, of which eleven macrocycles are from cyclization of the C1 to C6 positions of N-acetyl D-glucosamine derivatives and three others from C2 to C6 cyclization of functionalized D-glucosamine derivatives. These novel macrolactones have unique structures and demonstrate interesting anion binding properties, especially for chloride. The macrocycles containing two triazoles form complexes with copper sulfate, and they are effective ligands for copper sulfate mediated azide-alkyne cycloaddition reactions (CuAAC). In addition, several macrocycles show some selectivity for different alkynes.
Highlights
As shown in Scheme 1, the macrolactones with general structures 5A can be synthesized starting from the intermediate 3S, which was prepared from N-acetyl-D-glucosamine (NAG) [35]
By installing a suitable leaving group at the C-6 position and a nucleophile, such as a long-chain and triazole-containing carboxylate linked to the anomeric center, an intramolecular SN 2 reaction of the carboxylate with the leaving group is expected to form the macrolactones
Thin-layer chrochromatography (TLC) analysis was performed with aluminum-backed TLC plates with matography (TLC) analysis was performed with aluminum-backed TLC plates with UV
Summary
Macrocyclic compounds are important classes of molecules with many biological applications and useful for drug discovery [1,2]. Carbohydrate-based macrocyclic compounds have unique molecular architectures and many practical applications [3,4]. Existing and synthetic carbohydrate-based macrocycles have been utilized in drug discovery, molecular recognition, and as advanced functional materials [1,3,5,6,7]. Among the different classes of macrocycles, macrolactones are especially unique compounds that exhibit biological activities and often function as enzyme inhibitors; they showed applications in molecular recognition for supramolecular chemistry. Existing carbohydrate-based macrolactones or macrolides often exhibit many desirable biological activities for drug development [10,11,12]. Glucolipsin A (3) and analogs are natural products containing sugar dilactones—they are inhibitors for dual specific phosphatase Cdc25A [14]
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