Programmable one-pot synthesis of heparin pentasaccharides enabling access to regiodefined sulfate derivatives

Dey, Supriya; Wong, Chi‐Huey

doi:10.1039/c8sc01743c

Cited by 56 publications

(23 citation statements)

References 72 publications

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“…The heparin pentasaccharide with regiodefined sulfate patterns has been used as anti-coagulant and prepared previously in our laboratory using the programmable one-pot program 20 . In order to develop a better method to allow the flexibility to install the sulfate groups’ regioselectively, we have redesigned building blocks and reported the successful synthesis of heparin pentasaccharides for the regioselective introduction of the sulfate group 21 . These building blocks are now in the library of the Auto-CHO program.…”

Section: Resultsmentioning

confidence: 99%

Hierarchical and programmable one-pot synthesis of oligosaccharides

et al. 2018

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The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction. However, there were only about 50 BBLs with measured RRVs in the original library and the method could only synthesize small oligosaccharides due to the RRV ordering requirement. Here, we increase the library to include 154 validated BBLs and more than 50,000 virtual BBLs with predicted RRVs by machine learning. We also develop the software Auto-CHO to accommodate more data handling and support hierarchical one-pot synthesis using fragments as BBLs generated by the one-pot synthesis. This advanced programmable one-pot method provides potential synthetic solutions for complex glycans with four successful examples demonstrated in this work.

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Section: Resultsmentioning

confidence: 99%

Hierarchical and programmable one-pot synthesis of oligosaccharides

et al. 2018

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“…Recently, several research groups such as Lin et al [18], Dai et al [19], and Li et al [20] used the similar EDC + BA strategy to report the synthesis of protected fondaparinuxrelated pentasaccharide. Furthermore, 3 + 2 (EDC + BA) strategy was also utilized in the programmable one-pot method which was employed by Wong to synthesize one fondaparinux-related pentasaccharide [21]. In this method, the monosaccharide building blocks were selected from the OptiMer computer database for a given oligosaccharide.…”

Section: Synthesis Of Protected Pentasaccharide Edcbamentioning

confidence: 99%

Advances in Chemical Synthesis of Fondaparinux

Ding

Prasad²,

Wang

2019

Journal of Chemistry

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Fondaparinux (trade name Arixtra) is a safe and efficacious anticoagulant, and it is chemically related to low-molecular-weight heparins such as enoxaparin. Fondaparinux is a synthetic pentasaccharide, and its synthesis is difficult and expensive. The high cost of fondaparinux thwarts its extensive worldwide usage. Over the last two decades, several research groups and pharmaceutical companies have been interested in finding efficient and practical methods for its synthesis. The present review discusses those strategies and their pros and cons in a comparative account.

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“…The incorporation of one-pot-based strategies26 and iterative synthetic schemes has permitted an easier and faster access to very large heparin-like oligomers 27. Moreover, the programmed inclusion of different protective groups at specific positions allows further modifications of the original macromolecules 28. Some of these modifications also include heparin labelling to facilitate the purification steps29 or tagging to monitor the tissue distribution of heparin-based therapeutic candidates in biological studies 30.…”

Section: Introductionmentioning

confidence: 99%