Start Date

23-4-2026 12:00 AM

Description

Mannose chemistry is notoriously difficult due to the electronic structure of the molecule. The dipole moments on the molecule provide stability, meaning adding and removing substituents come with many obstacles. This results in numerous byproducts, prevents reactions from going quickly, or prevents the reaction from occurring at all. In this project, the issue of producing a mannose molecule with the desired leaving group for glycosylations is investigated using two different methods of synthesis of attaching 2-mercaptopyridimine to a benzylated mannose on carbon 1. These two methods investigate and aim to solve the issue of epoxide formation and the mannose molecule returning to its original form, as well as producing the desired product in substantial amounts. Ultimately, a mannose with the appropriate leaving group can be used in future glycosylation reactions that further investigate alpha and beta selectivity.

Research Highlights

The Problem: Standard mannose glycosyl donors protected with acetyl groups fail to produce desired 1-substituted products because acetyl deprotection leads to the formation of an intermediate epoxide that returns the molecule to its original mannose form. 

The Method: Researchers at Lindenwood University evaluated three synthetic pathways to attach a 2-mercaptopyridimine leaving group to C-1 of mannose, including bromination of benzylated mannose (Method 1), hydrolysis and acetylation of C-1 (Method 2), and a method involving bromination followed by CAN-mediated displacement (Method 3).  

Finding: Method 2 is identified as the most successful approach for attaching the leaving group, although it presents ongoing challenges regarding chemical yield and the formation of alpha and beta stereoisomeric mixtures.

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Apr 23rd, 12:00 AM

A Sticky Situation: Mannose Glycosides

Mannose chemistry is notoriously difficult due to the electronic structure of the molecule. The dipole moments on the molecule provide stability, meaning adding and removing substituents come with many obstacles. This results in numerous byproducts, prevents reactions from going quickly, or prevents the reaction from occurring at all. In this project, the issue of producing a mannose molecule with the desired leaving group for glycosylations is investigated using two different methods of synthesis of attaching 2-mercaptopyridimine to a benzylated mannose on carbon 1. These two methods investigate and aim to solve the issue of epoxide formation and the mannose molecule returning to its original form, as well as producing the desired product in substantial amounts. Ultimately, a mannose with the appropriate leaving group can be used in future glycosylation reactions that further investigate alpha and beta selectivity.

 

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