An Improved Approach for Practical Synthesis of 5-Hydroxymethyl-2′-deoxycytidine (5hmdC) Phosphoramidite and Triphosphate
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of Cyanoethyl-Protected 5hmdC Phosphoramidite (1)
2.2. Synthesis of 5hmdC Triphosphate (14)
3. Materials and Methods
3.1. General Methods
3.2. Synthetic Procedures of 5hmdC Phosphoramidite (1) and Intermediates (9–13)
3.3. Synthetic Procedures and Characterization Data of 5hmdC Triphosphate (14) and Intermediates (15–20)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Entry | Conditions | Yield (%) |
---|---|---|
1 | DMT-Cl (1.5 eq), 20 °C, Pyr, 12 h | 51 a |
2 | DMT-Cl (1.5 eq), 40 °C, Pyr, 12 h | 46 a |
3 | DMT-Cl (1.5 eq), 60 °C, Pyr, 12 h | 34 a,b |
4 | DMT-Cl (1.5 eq), DMAP (0.15 eq), 20 °C, Pyr, 6 h | 48 a |
5 | DMT-Cl (1.5 eq), DMAP (0.15 eq), DIPEA (2 eq), 20 °C, Pyr, 6 h | 54 a |
6 | DMT-trifluoroacetate (1.5 eq), 20 °C, THF, 12 h | No reaction |
7 | DMT-trifluoroacetate (1.5 eq), 20 °C, Pyr, 12 h | No reaction |
8 | DMT+BF4−(1.5 eq), Li2CO3, (5 eq), DIPEA (3 eq), 20 °C, THF, 5 h | 22 a |
9 | DMT+BF4− (1.5 eq), 20 °C, Pyr, 1 h | 85 |
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Yang, D.-Z.; Chen, Z.-Z.; Chi, M.; Dong, Y.-Y.; Pu, S.-Z.; Sun, Q. An Improved Approach for Practical Synthesis of 5-Hydroxymethyl-2′-deoxycytidine (5hmdC) Phosphoramidite and Triphosphate. Molecules 2022, 27, 749. https://doi.org/10.3390/molecules27030749
Yang D-Z, Chen Z-Z, Chi M, Dong Y-Y, Pu S-Z, Sun Q. An Improved Approach for Practical Synthesis of 5-Hydroxymethyl-2′-deoxycytidine (5hmdC) Phosphoramidite and Triphosphate. Molecules. 2022; 27(3):749. https://doi.org/10.3390/molecules27030749
Chicago/Turabian StyleYang, Dong-Zhao, Zhen-Zhen Chen, Mei Chi, Ying-Ying Dong, Shou-Zhi Pu, and Qi Sun. 2022. "An Improved Approach for Practical Synthesis of 5-Hydroxymethyl-2′-deoxycytidine (5hmdC) Phosphoramidite and Triphosphate" Molecules 27, no. 3: 749. https://doi.org/10.3390/molecules27030749