Investigation of Sulfur-related Influences on the Construction and Ring Opening of a Six-membered Cyclic Xanthate Derived from d-Thymidine and CS2.
- 1Departments of Chemistry, Texas A&M University, College Station, Texas77843, United States.
- 2Materials Science & Engineering, Texas A&M University, College Station, Texas77843, United States.
Abstract
With an interest in sustainable polymers derived from nucleoside building blocks, d-thymidine and carbon disulfide (CS2) were used as synthetic precursors to construct a trans-fused, 6,5-membered bicyclic xanthate, 3',5'-cyclic N3-(3-butenyl)-d-thymidine trans xanthate, for ring-opening polymerization (ROP) to yield stereo- and regiochemically defined homopolymer analogs of nucleic acids bearing thiocarbonate backbones. Screenings for CS2 insertion and succeeding cyclization to form the targeted monomer revealed two additional d-thymidine-derived cyclic moieties, including a xanthate and trithiocarbonate of cis-fused configurations, isolated in low yields. Therefore, ROP experiments using alkoxy-based initiators and organobase catalysts at room temperature and supporting DFT calculations for enthalpies of ring opening were extended to all three potential monomers, with only the trans-fused bicyclic xanthate undergoing ROP. Structural characterization by MALDI-TOF mass spectrometry and NMR spectroscopy of polymers obtained from ROPs of 3',5'-cyclic N3-(3-butenyl)-d-thymidine trans xanthate conducted at or somewhat below ambient temperatures indicated the presence of linear and cyclic species having primarily dimeric 5',5'-trithiocarbonate-co-3',3'-thionocarbonate connectivities from an alternating C-S and C-O cleavage pathway. Other minor trithiocarbonate, xanthate, and thionocarbonate functionalities were proposed to arise from backbiting reactions and/or minor regiorandom cleavages. In contrast, ROPs conducted at reduced temperatures (≤ -20 or -40 °C depending on the organobase) achieved selective C-S cleavage to yield 3',5'-xanthate-connected polymers of N3-(3-butenyl)-d-thymidine with more structural similarity to native DNA. These fundamental advances extend the breadth of nucleoside-derived polymers, emphasizing the influence of sulfur incorporation during monomer synthesis and upon subsequent ROPs, with outcomes being temperature-mediated alternating vs. unidirectional backbone compositional and structural regioregularity.
Related
- The utility of pyrimidine derivatives in the construction of five-membered non-azole-fused [d]pyrimidines: part III-synthetic strategies and biological applications
- In Situ FTIR Spectroscopy as a Kinetic Study Tool for Potassium Butyl Xanthate Industrial Production
- Oxidative Nucleophilic Aromatic ipso-Substitution for the Late-Stage Functionalization of Polycyclic Aromatic Hydrocarbons with Five-Membered Rings
- Tailored Nitrone [3+2] Dipolar Cycloaddition Enables the Elusive Synthesis of Structurally Complex Seven-Membered Heterocycles
- Copper-Catalyzed Asymmetric Remote ε-Arylation/Cyclization of Yne-Indole Esters with 5-Aminopyrazoles toward Polycyclic Fused Seven-Membered Azaheterocycles
BibTeX
@article{andras2026investigation,
title = {{Investigation of Sulfur-related Influences on the Construction and Ring Opening of a Six-membered Cyclic Xanthate Derived from d-Thymidine and CS2.}},
author = {Autumn M Andras and Nehal Fatima and Kai-Hua Mick Kuo and David K Tran and Donald J Darensbourg and Karen L Wooley},
journal = {Journal of the American Chemical Society},
year = {2026},
month = oct,
doi = {10.1021/jacs.6c15290},
url = {https://europepmc.org/article/MED/42913605},
note = {CC BY},
}
RIS
TY - JOUR
TI - Investigation of Sulfur-related Influences on the Construction and Ring Opening of a Six-membered Cyclic Xanthate Derived from d-Thymidine and CS2.
AU - Autumn M Andras
AU - Nehal Fatima
AU - Kai-Hua Mick Kuo
AU - David K Tran
AU - Donald J Darensbourg
AU - Karen L Wooley
PY - 2026
DA - 2026/10/01
JO - Journal of the American Chemical Society
DO - 10.1021/jacs.6c15290
UR - https://europepmc.org/article/MED/42913605
AB - With an interest in sustainable polymers derived from nucleoside building blocks, d-thymidine and carbon disulfide (CS2) were used as synthetic precursors to construct a trans-fused, 6,5-membered bicyclic xanthate, 3',5'-cyclic N3-(3-butenyl)-d-thymidine trans xanthate, for ring-opening polymerization (ROP) to yield stereo- and regiochemically defined homopolymer analogs of nucleic acids bearing thiocarbonate backbones. Screenings for CS2 insertion and succeeding cyclization to form the targeted monomer revealed two additional d-thymidine-derived cyclic moieties, including a xanthate and trithiocarbonate of cis-fused configurations, isolated in low yields. Therefore, ROP experiments using alkoxy-based initiators and organobase catalysts at room temperature and supporting DFT calculations for enthalpies of ring opening were extended to all three potential monomers, with only the trans-fused bicyclic xanthate undergoing ROP. Structural characterization by MALDI-TOF mass spectrometry and NMR spectroscopy of polymers obtained from ROPs of 3',5'-cyclic N3-(3-butenyl)-d-thymidine trans xanthate conducted at or somewhat below ambient temperatures indicated the presence of linear and cyclic species having primarily dimeric 5',5'-trithiocarbonate-co-3',3'-thionocarbonate connectivities from an alternating C-S and C-O cleavage pathway. Other minor trithiocarbonate, xanthate, and thionocarbonate functionalities were proposed to arise from backbiting reactions and/or minor regiorandom cleavages. In contrast, ROPs conducted at reduced temperatures (≤ -20 or -40 °C depending on the organobase) achieved selective C-S cleavage to yield 3',5'-xanthate-connected polymers of N3-(3-butenyl)-d-thymidine with more structural similarity to native DNA. These fundamental advances extend the breadth of nucleoside-derived polymers, emphasizing the influence of sulfur incorporation during monomer synthesis and upon subsequent ROPs, with outcomes being temperature-mediated alternating vs. unidirectional backbone compositional and structural regioregularity.
SN - 0002-7863
SN - 1520-5126
ER -