Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 14 min ago
PreprintCC BY-NCChemRxiv

Some Thioester Syntheses Love DIC: A Case Study on Functionalizing Amino Acids with O-Protected Mercaptoethanol

  • Victoria O. Kis1,2
  • A. Dina Dilinaer1,2
  • Mana Dashti1,2
  • Ezequiel Silva-Nigenda1,2
  • Dominique Leckie1,2
  • John J. Hayward1,2,3
  • John F. Trant1,2,3,4,5
5 affiliations
  1. 1Department of Chemistry and Biochemistry
  2. 2University of Windsor
  3. 3Department of Biomedical Sciences, University of Windsor, 401 Sunset Ave., Windsor, Canada, N9B 3P4
  4. 4WE-Spark Research Institute, 401 Sunset Ave., Windsor, Canada, N9B 3P4
  5. 5Binary Star Research Services
Open at sourcePDFDOICite

Abstract

Thioesters can be made through the formal condensation of a carboxylic acid and a thiol. This is generally accomplished using the same activated ester intermediates employed for amide synthesis; however, the yields are often far lower for the thiols. As part of our effort towards generating new biocompatible polymers, we need to access thioesters of amino acids in high efficiency and found that literature conditions for analogous systems provided extremely poor yields. Consequently, herein, we report our coupling reagent screening study for making thioesters between functionalized carboxylic acids (in the form of differentially protected amino acids) and multifunctional thiols including TBS-protected 2-mercaptoethanol, Fmoc-protected cysteine, and various aliphatic and aromatic thiols. Although there is no universal answer, we found that DIC, supplemented (or not) with HOBt in DMF reproducibly, and in the hands of multiple experimenters provided only with the written protocol, produced the highest yield both on small (low mg) and multigram scale.

Related

  1. Enhancing the robustness of thiol–thioester covalent adaptable networks through reversible thiol–Michael masking
    Anna Stasiuk, Alexis Millan, Mathias Destarac +2
    Polymer ChemistryPeer-reviewedPublisher termsFull text1 citedMaterials & polymersHAL
  2. Photocatalytic three-component cascade cyclization of α-keto acids, N-(o-cyanobiaryl)acrylamides, and elemental sulfur toward thioester-containing pyrido[4,3,2-gh]phenanthridines
    Xia Mi, He Chen, Shi-You Liu +2
    RSC advancesPeer-reviewedCC BY-NCFull textOrganic chemistryEurope PMCPMC
  3. Conetworks and Organogels of Poly(methyl acrylate) Crosslinked with Degradable, Disulfide and β-Thioester Containing Bisacrylate Macromonomer.
    Aiman Aitkazina, Ákos Szabó, László Trif +4
    Gels (Basel, Switzerland)Peer-reviewedCC BYFull textOrganic chemistryEurope PMC
  4. Enantioselective Total Syntheses of Bousigonine A and Bisleuconothine B
    Satoshi Matsumiya, Hayato Ishikawa
    ChemRxivPreprintLicence not statedGeneral chemistryChemRxiv
  5. Optimized Biomimetic Syntheses of Discorhabdin B and Aleutianamine Drives a Deeper Exploration of Their Anticancer Potential
    Nicholas L. Magann, Griffin L. Barnes, Ryan Schioldager +5
    Journal of the American Chemical SocietyPeer-reviewedLicence not statedFull text7 citedOrganic chemistryOpenAlex

Cite

BibTeXRIS
BibTeX
@misc{kis2026some,
  title = {{Some Thioester Syntheses Love DIC: A Case Study on Functionalizing Amino Acids with O-Protected Mercaptoethanol}},
  author = {Victoria O. Kis and A. Dina Dilinaer and Mana Dashti and Ezequiel Silva-Nigenda and Dominique Leckie and John J. Hayward and John F. Trant},
  howpublished = {ChemRxiv},
  year = {2026},
  month = aug,
  doi = {10.26434/chemrxiv.15008056/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008056/v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Some Thioester Syntheses Love DIC: A Case Study on Functionalizing Amino Acids with O-Protected Mercaptoethanol
AU  - Victoria O. Kis
AU  - A. Dina Dilinaer
AU  - Mana Dashti
AU  - Ezequiel Silva-Nigenda
AU  - Dominique Leckie
AU  - John J. Hayward
AU  - John F. Trant
PY  - 2026
DA  - 2026/08/30
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15008056/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008056/v1
AB  - Thioesters can be made through the formal condensation of a carboxylic acid and a thiol. This is generally accomplished using the same activated ester intermediates employed for amide synthesis; however, the yields are often far lower for the thiols. As part of our effort towards generating new biocompatible polymers, we need to access thioesters of amino acids in high efficiency and found that literature conditions for analogous systems provided extremely poor yields. Consequently, herein, we report our coupling reagent screening study for making thioesters between functionalized carboxylic acids (in the form of differentially protected amino acids) and multifunctional thiols including TBS-protected 2-mercaptoethanol, Fmoc-protected cysteine, and various aliphatic and aromatic thiols. Although there is no universal answer, we found that DIC, supplemented (or not) with HOBt in DMF reproducibly, and in the hands of multiple experimenters provided only with the written protocol, produced the highest yield both on small (low mg) and multigram scale.
ER  -