The most typical cyclodextrins are α-, β-, and γ-cyclodextrin, which consist of six, seven, and eight glucopyranose units, respectively, in a ring. Natural cyclodextrins consist of many free hydroxyl groups (each sugar unit contributes three free hydroxyl groups), and these hydroxyl groups can be substituted by other functional groups in some appropriate ways, thus providing cyclodextrins with a much wider range of potential utilities. The more we know about these macrocyclic molecules, the more applications we will find; for example, they can be used in materials science, pharmaceutical science, supramolecular chemistry, catalytic chemistry, etc. However, we think that the applications of cyclodextrins are still underestimated, especially as new selectively functionalized cyclodextrins are continually being actively developed. In this review we will discuss some of the progress in selective functionalization of cyclodextrins and their applications in biodelivery that scientists have explored.

Amatoxins, a class of highly toxic octapeptides isolated from mushroom Amanita phalloides, are potential payloads for ADCs. The total synthesis of amaninamide and α-amanitin is a formidable synthetic challenge for chemists and medical biologists. Herein, we report the first multigram scalable practical total synthesis of the amaninamide and α-amanitin via a concise approach through twelve isolated intermediates with total yields of 3.69% and 1.73%, respectively, which are the highest yields reported to date. A new synthetic strategy was developed for amatoxins. The key to this practical total synthesis was the scalable asymmetric synthesis of the unnatural chiral amino acids DHIle and 6-Htp (>500 G). An asymmetric Rh/Cu cocatalyzed allylation was developed to achieve the DHIle intermediate in 95% yield, > 99% ee and > 9:1 dr, and DHIle was synthesized through the developed method and Sharpless asymmetric dihydroxylation. This is the most efficient practical total synthesis of amaninamide and α-amanitin, solving the world's bottleneck challenges of amanitin-based ADCs-targeted anticancer drugs.