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. 2022 Apr 14;27(8):2528.
doi: 10.3390/molecules27082528.

Stereoselective Synthesis of β-Glycinamide Ribonucleotide

Lisa Ngu  1 , Debarpita Ray  1 , Samantha S Watson  1 , Penny J Beuning  1 , Mary Jo Ondrechen  1 , George A O'Doherty  1
Affiliations

Stereoselective Synthesis of β-Glycinamide Ribonucleotide

Lisa Ngu et al. Molecules. .

Abstract

A diastereoselective synthesis of the β-anomer of glycinamide ribonucleotide (β-GAR) has been developed. The synthesis was accomplished in nine steps from D-ribose and occurred in 5% overall yield. The route provided material on the multi-milligram scale. The synthetic β-GAR formed was remarkably resistant to anomerization both in solution and as a solid.

Keywords: GART; stereoselective synthesis; β-GAR; β-glycinamide ribonucleotide.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
GART mediated transfer of formyl group from 10-formyl-THF to GAR.
Scheme 2
Scheme 2
Previous approaches to GAR.
Scheme 3
Scheme 3
Previous issues regarding anomeric stereochemistry in β-GAR synthesis.
Scheme 4
Scheme 4
Synthesis of D-ribofuranosyl azide (3).
Scheme 5
Scheme 5
Switching from isopropylidene to benzylidene protected ribofuranosyl azide (5).
Scheme 6
Scheme 6
Synthesis and separation of Cbz-Glycinamide of benzylidene protected-d-ribose.
Scheme 7
Scheme 7
Installation of phosphate and deprotection.
Scheme 8
Scheme 8
Isomerization under stressed conditions.
Figure 1
Figure 1
(a) 1H-NMR of a ~1:1 mixture of α- and β-GAR; (b) pure β-GAR.
Figure 2
Figure 2
Increase in absorbance (295 nm) as a function of time; average of two experiments.
See this image and copyright information in PMC

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