PHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide
The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and photochemical studies showed an absorption maximum at λ = 330 nm and a quantum yield for release of 11% that are dependent upon both pH and solvent. While the acyl carbamate releases nicotinamide efficiently, a simpler amide linker was inert to photocleavage. This photocaged nicotinamide has significant advantages with respect to quantum yield, absorbance wavelength, rate of release, and solubility that make it the first practical example of a photocaged amide.
Salahi, Farbod,Purohit, Vatsal,Ferraudi, Guillermo,Stauffacher, Cynthia,Wiest, Olaf,Helquist, Paul
p. 2547 - 2550
(2018/05/22)
Investigation of novel pesticides with insecticidal and antifungal activities: Design, synthesis and SAR studies of benzoylpyrimidinylurea derivatives
In order to find pesticides with insecticidal and antifungal activities, a series of novel benzoyl pyrimidinylurea derivatives were designed and synthesized. All target compounds were identified by 1H-NMR spectroscopy and HRMS. Insecticidal and antifungal activity of these compounds were evaluated and the structure-activity relationships (SAR) were clearly and comprehensively illustrated. Compound 7, with low toxicity to zebrafish (LC50 = 378.387 μg mL?1) showed 100% inhibition against mosquito (Culex pipiens pallens) at 0.25 μg mL?1. Both compounds 19 and 25 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 13 phytopathogenic fungi), which were better than those of the commercial pesticide pyrimethanil (>50% inhibitory activities against eight phytopathogenic fungi). Furthermore, compounds 19 and 25 exhibited protective activity against Sclerotinia sclerotiorum on leaves of Brassica oleracea L. during in vivo experiments.
Development of carbamate-tethered coumarins as phototriggers for caged nicotinamide
The syntheses of 7-diethylaminocoumarin- or modified DEACM-nicotinamide and 6-bromo-7-methoxycoumarin- or BMCM-nicotinamide have been accomplished by reaction of nicotinoyl isocyanate with the corresponding coumarin allylic alcohol derivatives. The resulting compounds contain an N-acyl O-alkyl carbamate as a new type of linkage for the caging of nicotinamide with a coumarin phototrigger, which undergoes cleavage upon photolysis. Our design of specific caged-nicotinamides was based upon NBO and TD-FT calculations to predict absorption wavelengths and photocleavage potential. This work provides a potentially general method for the caging of amides with coumarin photolabile protecting groups.
Bourbon, Pauline,Peng, Qian,Ferraudi, Guillermo,Stauffacher, Cynthia,Wiest, Olaf,Helquist, Paul
supporting information
p. 6321 - 6324
(2013/11/19)
Mutual prodrugs containing bio-cleavable and drug releasable disulfide linkers
We report herein the design and synthesis of several representative examples of novel mutual prodrugs containing nine distinct types of self-immolative drug-releasable disulfide linkers with urethane, ester, carbonate, or imide linkages between the linker and any two amine/amide/urea (primary or secondary) or carboxyl or hydroxyl (including phenolic)-containing drugs. We also report drug release profiles of a few representative mutual prodrugs in biological fluids such as simulated gastric fluid and human plasma. We also propose plausible mechanisms of drug release from these mutual prodrugs. We have also conducted a few mechanistic studies based on suggested sulfhydryl-assisted cleavage of mutual prodrugs and characterized a few important metabolites to give support to the proposed mechanism of drug release from the reported mutual prodrugs.