Cycloadditions as a Sweet Route to ‘Double C-Glycosylation’
Abstract
1. Introduction
2. Materials and Methods
2.1. Preparation of Pyrylium Salt (2)
2.2. General Procedure or Preparation of Cycloadducts
2.3. Single Crystal X-Ray Diffraction
3. Results and Discussion
3.1. Initial Exploration of the Cycloaddition Reaction
3.2. Solvent Screening
3.3. Base Screening
3.4. Exploring Substrate Scope
3.5. Assessment of Antibiotic Activity
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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6 | 9b | |
---|---|---|
formula | C14H16O6 | C17H12O4 |
fw | 280.27 | 280.27 |
crystal description | Colourless plate | Yellow prism |
crystal size [mm3] | 0.24 × 0.18 × 0.02 | 0.12 × 0.09 × 0.05 |
space group | P | P |
a [Å] | 9.2341 (3) | 7.884 (3) |
b [Å] | 10.6447 (5) | 8.055 (3) |
c [Å] | 14.4081 (6) | 10.842 (3) |
α [°] | 77.390 (4) | 92.509 (17) |
β [°] | 74.942 (4) | 108.668 (19) |
γ [°] | 89.491 (3) | 95.313 (13) |
vol [Å]3 | 1332.89 (10) | 647.5 (4) |
Z | 4 | 2 |
ρ (calc) [g/cm3] | 1.397 | 1.437 |
μ [mm−1] | 0.928 | 0.850 |
F(000) | 592 | 292 |
reflections collected | 12704 | 6785 |
independent reflections (Rint) | 4770 (0.0308) | 2308 (0.0385) |
parameters, restraints | 369, 0 | 193, 0 |
GoF on F2 | 1.072 | 1.129 |
R1 [I > 2σ(I)] | 0.0428 | 0.0644 |
wR2 (all data) | 0.1270 | 0.1358 |
largest diff. peak/hole [e/Å3] | 0.220, −0.241 | 0.512, −0.6620 |
Entry | Solvent | Isolated Yield of Diastereoisomer 3a (%) | Isolated Yield of Diastereoisomer 3b (%) |
---|---|---|---|
1 | Neat | 7 | - |
2 | Dichloromethane | 10 | - |
3 | Toluene | 6 | - |
4 | Chloroform | 14 | - |
5 | 1,4-Dioxane | 7 | - |
6 | Methanol | 5 | - |
7 | Acetonitrile | 12 | - |
8 | Tetrahydrofuran | 17 | 7 |
9 | Ethyl Acetate | 9 | - |
10 | Hexane | 9 | - |
11 | Diethylether | 17 | - |
Entry | Base | Equivalents | pKa | Yield 3a (%) |
---|---|---|---|---|
1 | N,N-Dimethylaniline | 1.5 | 5.2 | 17 |
2 | 3 | 14 | ||
3 | 2,6-Lutidine | 1.5 | 6.7 | - |
4 | 3 | - | ||
5 | Pyridine | 1.5 | 5.3 | - |
6 | 3 | 23 | ||
7 | N,N-Diisopropylethylamine | 1.5 | 10.6 | 25 |
8 | 3 | 13 | ||
9 | 1,8-Diazabicyclo[5.4.0]undec-7-ene | 1.5 | 12.5 | - |
10 | 3 | - | ||
11 | 4-(Dimethylamino)pyridine | 1.5 | 9.7 | 34 † |
12 | 3 | 37 † |
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Mahoney, K.P.P.; Lynch, R.; Bown, R.T.; Sharma, S.V.; Chueakwon, P.; Stephenson, G.R.; Cordes, D.B.; Slawin, A.M.Z.; Goss, R.J.M. Cycloadditions as a Sweet Route to ‘Double C-Glycosylation’. Biomolecules 2025, 15, 905. https://doi.org/10.3390/biom15060905
Mahoney KPP, Lynch R, Bown RT, Sharma SV, Chueakwon P, Stephenson GR, Cordes DB, Slawin AMZ, Goss RJM. Cycloadditions as a Sweet Route to ‘Double C-Glycosylation’. Biomolecules. 2025; 15(6):905. https://doi.org/10.3390/biom15060905
Chicago/Turabian StyleMahoney, Kevin P. P., Rosemary Lynch, Rhea T. Bown, Sunil V. Sharma, Piyasiri Chueakwon, G. Richard Stephenson, David B. Cordes, Alexandra M. Z. Slawin, and Rebecca J. M. Goss. 2025. "Cycloadditions as a Sweet Route to ‘Double C-Glycosylation’" Biomolecules 15, no. 6: 905. https://doi.org/10.3390/biom15060905
APA StyleMahoney, K. P. P., Lynch, R., Bown, R. T., Sharma, S. V., Chueakwon, P., Stephenson, G. R., Cordes, D. B., Slawin, A. M. Z., & Goss, R. J. M. (2025). Cycloadditions as a Sweet Route to ‘Double C-Glycosylation’. Biomolecules, 15(6), 905. https://doi.org/10.3390/biom15060905