Heteroglycoclusters through Unprecedented Orthogonal Chemistry Based on N‐Alkylation of N‐Acylhydrazone

Orthogonal chemistry is a valuable tool in the preparation of complex molecules as heteroglycoclusters. Unfortunately, selective heteroconjugation of multifunctional starting materials remains a usually challenging problem to overcome. Herein, we report the first report on harnessing N‐alkylation of N‐acylhydrazone as a key step in the orthogonal synthesis. Sequentially associated with the azido‐alkyne click chemistry, it stands out as a new and straightforward synthetic method of glycoconjugate small molecules, heterodisaccharides, and heteroglycoclusters based on cone p‐tBu‐calix[4]arene and 1,3‐alt p‐tBu‐thiacalix[4]arene with potential drug‐like properties. We report a new orthogonal strategy involving the N‐alkylation of N‐acylhydrazone as a key step. When followed by azido‐alkyne click chemistry, it represents a new and straightforward synthetic method to prepare N‐alkyl‐NAH glycoconjugates of small molecules, heterodisaccharides, and heteroglycoclusters‐based on cone p‐tBu‐calix[4]arene and 1,3‐alt p‐tBu‐thiacalix[4]arene with potential drug‐like properties.