Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents
Amine-targeting reactions that work under biocompatible conditions or in water are green processes that are extremely useful for the synthesis of functional materials and biotherapeutics. Unfortunately, despite the usefulness of this reaction, there are very few good amine-specific click methods rep...
| Main Authors: | , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/169291 |
| _version_ | 1824455199800950784 |
|---|---|
| author | Teng, Shenghan Ng, Elvis Wang Hei Zhang, Zhenguo Soon, Chee Ning Xu, Hailun Li, Ruifang Hirao, Hajime Loh, Teck-Peng |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Teng, Shenghan Ng, Elvis Wang Hei Zhang, Zhenguo Soon, Chee Ning Xu, Hailun Li, Ruifang Hirao, Hajime Loh, Teck-Peng |
| author_sort | Teng, Shenghan |
| collection | NTU |
| description | Amine-targeting reactions that work under biocompatible conditions or in water are green processes that are extremely useful for the synthesis of functional materials and biotherapeutics. Unfortunately, despite the usefulness of this reaction, there are very few good amine-specific click methods reported thus far. Here, we report an amine-specific click reagent using alkynone β-trifluoroborates as the electrophiles. These boron-containing alkynyl reagents exhibit extremely high chemoselectivity toward amines even in the presence of thiols. The resulting oxaboracycle products are bench-stable, displaying the reactivities of both organoborates and enaminones. Intrinsic advantages of this methodology include benign reaction conditions, operational simplicity, remarkable product stability, and excellent chemoselectivity, which satisfy the criteria of click chemistry and demonstrate the high potential in bioconjugation. Hence, this water-based chemical approach is also applicable to the modification of native amino acids, peptides, and proteins. Ultimately, the essential role of water during the reaction was elucidated. |
| first_indexed | 2025-02-19T03:34:25Z |
| format | Journal Article |
| id | ntu-10356/169291 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:34:25Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1692912023-07-14T15:31:48Z Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents Teng, Shenghan Ng, Elvis Wang Hei Zhang, Zhenguo Soon, Chee Ning Xu, Hailun Li, Ruifang Hirao, Hajime Loh, Teck-Peng School of Chemistry, Chemical Engineering and Biotechnology Science::Chemistry Alkynones Alkynyls Amine-targeting reactions that work under biocompatible conditions or in water are green processes that are extremely useful for the synthesis of functional materials and biotherapeutics. Unfortunately, despite the usefulness of this reaction, there are very few good amine-specific click methods reported thus far. Here, we report an amine-specific click reagent using alkynone β-trifluoroborates as the electrophiles. These boron-containing alkynyl reagents exhibit extremely high chemoselectivity toward amines even in the presence of thiols. The resulting oxaboracycle products are bench-stable, displaying the reactivities of both organoborates and enaminones. Intrinsic advantages of this methodology include benign reaction conditions, operational simplicity, remarkable product stability, and excellent chemoselectivity, which satisfy the criteria of click chemistry and demonstrate the high potential in bioconjugation. Hence, this water-based chemical approach is also applicable to the modification of native amino acids, peptides, and proteins. Ultimately, the essential role of water during the reaction was elucidated. Ministry of Education (MOE) Nanyang Technological University Published version We gratefully acknowledge the financial support from Distinguished University Professor grant (Nanyang Technological University); AcRF Tier 1 grant from the Ministry of Education of Singapore (RT14/20); and the Agency for Science, Technology, and Research (A*STAR) under its MTC Individual Research grant (M21K2c0114) and RIE2025 MTC Programmatic Fund (M22K9b0049) for T.-P.L. We also thank a Changjiang Scholarship, a university development fund (UDF01001996) from the Chinese University of Hong Kong, Shenzhen and a Warshel Institute for Computational Biology fund (C10120180043) for H.H. 2023-07-11T06:04:47Z 2023-07-11T06:04:47Z 2023 Journal Article Teng, S., Ng, E. W. H., Zhang, Z., Soon, C. N., Xu, H., Li, R., Hirao, H. & Loh, T. (2023). Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents. Science Advances, 9(17), eadg4924-. https://dx.doi.org/10.1126/sciadv.adg4924 2375-2548 https://hdl.handle.net/10356/169291 10.1126/sciadv.adg4924 37126553 2-s2.0-85157981278 17 9 eadg4924 en RT14/20 M21K2c0114 M22K9b0049 Science Advances © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). application/pdf |
| spellingShingle | Science::Chemistry Alkynones Alkynyls Teng, Shenghan Ng, Elvis Wang Hei Zhang, Zhenguo Soon, Chee Ning Xu, Hailun Li, Ruifang Hirao, Hajime Loh, Teck-Peng Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents |
| title | Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents |
| title_full | Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents |
| title_fullStr | Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents |
| title_full_unstemmed | Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents |
| title_short | Alkynone β-trifluoroborates: a new class of amine-specific biocompatible click reagents |
| title_sort | alkynone β trifluoroborates a new class of amine specific biocompatible click reagents |
| topic | Science::Chemistry Alkynones Alkynyls |
| url | https://hdl.handle.net/10356/169291 |
| work_keys_str_mv | AT tengshenghan alkynonebtrifluoroboratesanewclassofaminespecificbiocompatibleclickreagents AT ngelviswanghei alkynonebtrifluoroboratesanewclassofaminespecificbiocompatibleclickreagents AT zhangzhenguo alkynonebtrifluoroboratesanewclassofaminespecificbiocompatibleclickreagents AT sooncheening alkynonebtrifluoroboratesanewclassofaminespecificbiocompatibleclickreagents AT xuhailun alkynonebtrifluoroboratesanewclassofaminespecificbiocompatibleclickreagents AT liruifang alkynonebtrifluoroboratesanewclassofaminespecificbiocompatibleclickreagents AT hiraohajime alkynonebtrifluoroboratesanewclassofaminespecificbiocompatibleclickreagents AT lohteckpeng alkynonebtrifluoroboratesanewclassofaminespecificbiocompatibleclickreagents |