Abstract
Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) “click chemistry” has proven to be a powerful tool in the realm of glycosylation, allowing for efficient attachment of very large carbohydrates to other complex molecules such as proteins, nucleic acids, or polymers.Preliminary data collected from the Krauss group suggested that silyl protected alkynes on 5-ethynyl-2’deoxyuridine (EdU) react in click reactions with similar or higher rates of reaction compared to free alkynes. The efficiency of the click reactions was therefore tested with different silyl protecting groups of different sizes. The rate of reaction was found to decrease noticeably as the protecting group increased in steric bulk. The trimethyl silyl (TMS) protecting group performs the best, reaching full conversion within one hour, although this is no faster than unprotected EdU. The triethyl silyl (TES) protecting group and triisopropyl protecting group (TIPS) are unable to efficiently participate in the click reaction, needing upwards of 24 hours to reach full conversion or never reacting at all. The difference in performance is likely due to the kinetics of the bond: TMS will cleave quickly while larger protecting groups are removed much more slowly. The faster deprotection allows for a faster rate of reaction. The presence of copper facilitates the rate of deprotection. While copper is required to cleave off the TES protecting group, it is not required to remove the TMS group. Additionally, the conjugation between the pyrimidine ring and the alkyne slightly facilitates the removal of the protecting group; however, separating the alkyne from the ring by several saturated carbons does not prevent either deprotection or click reaction from occurring. Overall, the observation that silyl-protected EdU could react faster than unprotected EdU in click reactions was not reproduced. TMS protected alkynes can undergo click reaction; however, TES and TIPS protected alkynes cannot. While silyl protection does not increase the rate of CuAAC, it may still prove useful in avoiding unwanted side reactions of alkynes such as hydration.