Automated, Multistep Continuous‐Flow Synthesis of 2,6‐Dideoxy and 3‐Amino‐2,3,6‐trideoxy Monosaccharide Building Blocks

Abstract

An automated continuous flow system capable of producing protected deoxy‐sugar donors from commercial material is described. Four 2,6‐dideoxy and two 3‐amino‐2,3,6‐trideoxy sugars with orthogonal protecting groups were synthesized in 11–32 % overall yields in 74–131.5 minutes of total reaction time. Several of the reactions were able to be concatenated into a continuous process, avoiding the need for chromatographic purification of intermediates. The modular nature of the experimental setup allowed for reaction streams to be split into different lines for the parallel synthesis of multiple donors. Further, the continuous flow processes were fully automated and described through the design of an open‐source Python‐controlled automation platform.

Synthesis and Glycosidation of Anomeric Halides: Evolution from Early Studies to Modern Methods of the 21st Century

“…Upon achieving a reliable and simple platform for completely automated glycosylation, anybody should be able to perform automated synthesis of glycans. Machine-assisted synthesis will help to eliminate variability, and to accurately reproduce experiments multiple times by different users. ,,− ,,− Synthesis of glycans using user-friendly automated platforms will accelerate discovery of new carbohydrate-based or carbohydrate-containing diagnostics, − pharmaceuticals, ,− and vaccines. − This will lead to innovations in many scientific disciplines and can significantly impact technology, society, the economy, and public health.…”

“…Lin et al treated unprotected sugars with LiClO 4 -Ac 2 O followed by the reaction with HBr-AcOH . Recently, Bennett, Pohl, and co-workers developed a continuous flow platform for the synthesis of orthogonally protected monosaccharide building blocks . One relevant example includes acetylation and bromination of unprotected sugars performed in a single step.…”

Integrated Chemoenzymatic Approach to Streamline the Assembly of Complex Glycopeptides in the Liquid Phase

“…Additionally, the separation process in LPPS can be accomplished by extraction or precipitation based on tag technologies − and diafiltration technologies. , Recently, a novel liquid peptide synthesis approach was introduced by Livingston and Albericio via one-pot nanostar sieving . Moreover, several automated solution-phase synthesis platforms such as fluorous tag-assisted synthesis of glycans, sulfonate tag-supported enzymatic assembly of complex oligosaccharides, and fast-flow synthesis of deoxy-sugars and oligonucleotides have been developed to enable easy access to various biomolecules. Given these impressive advancements in the liquid-phase assembly of peptides, oligosaccharides, and oligonucleotides, we reported here a chemoenzymatic approach to streamline the preparation of diverse and complex glycopeptides in the liquid phase (Figure ).…”

The assembly of integrated continuous flow platform for on-demand rosiglitazone and pioglitazone synthesis

“…19,22 Recently, integrated continuous flow technology has emerged as a fantastic man-made tool that could address batch-related problems. [26][27][28][29][30] Several integrated chemical processing machines have been developed in recent years that enable in-line ultra-fast reactions, extraction, separation, and purification, thereby enhancing the applicability of the continuous flow process. [31][32][33][34][35] Several research groups have now achieved the laboratory scale API production; however scale up in the flow process seems a big challenge.…”