Molecular Design and Synthesis of Thiophene-Based O-Nitrobenzyl Group: A Visible Light-Absorbing Pro-Fluorescent Photoremovable Protecting Group for Hydroxamic Acid Synthesis.
Disciplines
Materials Chemistry | Organic Chemistry | Physical Chemistry
Abstract (300 words maximum)
Hydroxamic acids (HAs) are a class of organic compounds widely known for their use as precursors of anticancer drugs such as Trichostatin A, a powerful tumor cell inhibitor. Despite their widespread use, HAs are difficult to synthesize and purify due to their high reactivity and the formation of numerous polysubstituted by-products. To address the drawbacks associated with HA synthesis and purification, scientists explored the chemistry of protecting groups (PGs), which are are compounds used to mask the reactivity of highly reactive functional groups. Nonetheless, as the number of similar PGs within a molecule increases, the selective deprotection of individual PGs with harsh acidic and basic conditions becomes difficult. As a result, photolabile protecting groups (PPGs) especially ortho-nitrobenzyl (o-NB) PPGs, a less harsh approach is employed because only light is required to cleave the PPGs. However, most o-NB PPGs absorb in the ultraviolet region (UV) of the electromagnetic spectrum, making them unsuitable for biological applications. In this study, we have solved the problem of HA traditional synthesis and purification by designing and synthesizing a series of visible light-absorbing o-NB PPGs. In our method, we reduced the formation of undesired by-products and only produce one diagnostic fluorescent by-product, which is used to quantify the amount of HAs produced by measuring the absorption and emission intensity and wavelength. This is a preferable synthetic route because deprotecting these PPGs with visible light, a less harsh method, is required to release HAs in very high yields. The stability of the o-NB PPGs is also confirmed by monitoring their shelf life using 1H NMR spectroscopy and selectively deprotecting standard PGs from our PPGs using harsh conditions that do not cleave the HA moiety. Most notably, our visible-light absorption PPGs have potential applications in biological systems, specifically drug delivery and cancer treatment.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Carl Saint-Louis
Molecular Design and Synthesis of Thiophene-Based O-Nitrobenzyl Group: A Visible Light-Absorbing Pro-Fluorescent Photoremovable Protecting Group for Hydroxamic Acid Synthesis.
Hydroxamic acids (HAs) are a class of organic compounds widely known for their use as precursors of anticancer drugs such as Trichostatin A, a powerful tumor cell inhibitor. Despite their widespread use, HAs are difficult to synthesize and purify due to their high reactivity and the formation of numerous polysubstituted by-products. To address the drawbacks associated with HA synthesis and purification, scientists explored the chemistry of protecting groups (PGs), which are are compounds used to mask the reactivity of highly reactive functional groups. Nonetheless, as the number of similar PGs within a molecule increases, the selective deprotection of individual PGs with harsh acidic and basic conditions becomes difficult. As a result, photolabile protecting groups (PPGs) especially ortho-nitrobenzyl (o-NB) PPGs, a less harsh approach is employed because only light is required to cleave the PPGs. However, most o-NB PPGs absorb in the ultraviolet region (UV) of the electromagnetic spectrum, making them unsuitable for biological applications. In this study, we have solved the problem of HA traditional synthesis and purification by designing and synthesizing a series of visible light-absorbing o-NB PPGs. In our method, we reduced the formation of undesired by-products and only produce one diagnostic fluorescent by-product, which is used to quantify the amount of HAs produced by measuring the absorption and emission intensity and wavelength. This is a preferable synthetic route because deprotecting these PPGs with visible light, a less harsh method, is required to release HAs in very high yields. The stability of the o-NB PPGs is also confirmed by monitoring their shelf life using 1H NMR spectroscopy and selectively deprotecting standard PGs from our PPGs using harsh conditions that do not cleave the HA moiety. Most notably, our visible-light absorption PPGs have potential applications in biological systems, specifically drug delivery and cancer treatment.