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A new kind of photolabile protecting group (PLPG) for carboxyl moieties was designed and synthesized as the linker between resin and peptide. This group can be used for the protection of amino acid carboxyl groups. The peptide was synthesized on Nph (2-hydroxy-3-(2-nitrophenyl)-heptanoic acid)-derivatized resins and could be cleaved under UV exposure, thus avoiding the necessity for harsh acid-mediated resin cleavage. The PLPG has been successfully used for solid-phase synthesis of peptides., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

Cholesterol-lowering statin drugs are among the most frequently prescribed for reducing human blood cholesterol and they have been detected as contaminants in natural waters. In this study the photochemical behavior of atorvastatin (lipitor) was investigated at two different concentrations of 35.8 μM (20 mg L(-1)) and 35.8 nM (20 μg L(-1)) using a solar simulator and a UV reactor. Photochemical fate in natural waters can be described in most cases by the sum of the loss due to hydrolysis, direct photolysis, and, reaction with hydroxyl radical (•OH), singlet oxygen ((1)O(2)) (or O(2) ((1)D)), and excited state dissolved organic matter (DOM). The absolute bimolecular reaction rate constant with OH was measured, using pulsed radiolysis, (1.19 ± 0.04) × 10(10) M(-1) s(-1). The reaction rate constant of (1)O(2) was determined to be (3.1 ± 0.2) × 10(8) M(-1) s(-1). Under the experimental conditions used, at high atorvastatin concentration (35.8 μM) the contribution of singlet oxygen ((1)O(2)) to the photodegradation of atorvastatin in natural waters was higher than that of hydroxyl radical, and accounted for up to 23% of the loss in aqueous solutions. Whereas, at a concentration of 35.8 nM, (1)O(2) (and •OH) both played a minor role in the removal of this compound. Lastly, it also appears that atorvastatin reacts with (3)DOM* contributing to its loss in simulated natural waters., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Atorvastatin calcium (ATV) is one of the most frequently prescribed drugs worldwide. Among the adverse effects observed for this lipid-lowering agent, clinical cases of cutaneous adverse reactions have been reported and associated with photosensitivity disorders. Previous work dealing with ATV photochemistry has shown that exposure to natural sunlight in aqueous solution leads to photoproducts resulting from oxidation of the pyrrole ring and from cyclization to a phenanthrene derivative. Laser flash photolysis of ATV, at both 266 and 308 nm, led to a transient spectrum with two maxima at lambda= 360 and lambda= 580 nm (tau= 41 micro), which was assigned to the primary intermediate of the stilbene-like photocyclization. On the basis of the absence of a triplet-triplet absorption, the role of the parent drug as singlet oxygen photosensitizer can be discarded. By contrast, a stable phenanthrene-like photoproduct would be a good candidate to play this role. Laser flash photolysis of this compound showed a triplet-triplet transient absorption at lambdamax = 460 nm with a lifetime of 26 micro, which was efficiently quenched by oxygen (kq = 3 (+/-0.2) x 10(9) M(-1) s(-1)). Its potential to photosensitize formation of singlet oxygen was confirmed by spin trapping experiments, through conversion of TEMP to the stable free radical TEMPO. The photoreactivity of the phenanthrene-like photoproduct was investigated using Trp as a marker. The disappearance of the amino acid fluorescence (lambdamax = 340 nm) after increasing irradiation times at 355 nm was taken as a measurement of photodynamic oxidation. To confirm the involvement of a type II mechanism, the same experiment was also performed in D2O; this resulted in a significant enhancement of the reaction rate. On the basis of the obtained photophysical and photochemical results, the phototoxicity of atorvastatin can be attributed to singlet oxygen formation with the phenanthrene-like photoproduct as a photosensitizer.

A novel three-stage light irradiation strategy in the submerged fermentation of medicinal mushroom Ganoderma lucidum for the efficient production of bioactive metabolites ganoderic acid (GA) and Ganoderma polysaccharides was developed. Significance of light quality, i.e., blue light (390-500 nm, lambda(max) = 470 nm), red light (560-700 nm, lambda(max) = 625 nm), and white light (400-740 nm, lambda(max) = 550 nm), was studied at first. Interestingly, there was a gradual decrease trend of GA content after the culture of day 2 when the maximal GA content was obtained, while GA content decreased slowly under white light irradiation after day 6. The dark environment was favorable to the specific GA biosynthesis (i.e., GA content) before day 6, and after that the optimum was white light irradiation. A relatively lower irradiation density of white light (i.e., 0.94 and 2.82 W/m(2)) was beneficial for the specific GA biosynthesis before day 6, while GA content was higher under higher irradiation density of white light (i.e., 4.70 and 9.40 W/m(2)) at the later-stage of cultivation. 4.70 W/m(2) white light irradiation culture was the best from the viewpoint of GA accumulation. Therefore, a two-stage light irradiation strategy by combing the first 2 days dark culture with the following 4.70 W/m(2) white light irradiation culture was developed. The highest GA production in the two-stage culture was 276.0 +/- 12.5 mg/L, which was increased by 19% compared to 4.70 W/m(2) white light irradiation culture (i.e., 232.4 +/- 15.8 mg/L) and by 178% compared to the dark culture (i.e., 99.4 +/- 1.0 mg/L). Although there still existed a gradual decrease trend of GA content after day 2 when the maximal GA content was obtained in the two-stage culture. Following three-stage light irradiation strategy was further demonstrated in order to turn around the sharp decrease of GA content after day 2. The first-stage was the 2-day dark culture; the second-stage was the following six-day 0.94 W/m(2) white light irradiation culture, and the third-stage was 4.70 W/m(2) white light irradiation culture until the end of fermentation. During the three-stage culture of G. lucidum, the gradual decrease trend of GA content after day 2 was turned around, which suggested that 0.94 W/m(2) white light irradiation was beneficial for the metabolic flux towards the GA biosynthesis. The maximal GA content of 3.1 +/- 0.1 mg/100 mg DW was obtained, which was higher by 41% compared to the two-stage culture. The maximal GA production (i.e., 466.3 +/- 24.1 mg/L) and productivity (i.e., 38.9 mg/L per day) in the three-stage culture were 69 and 101% higher than those obtained in the two-stage culture. This is the first report investigating the significance of light irradiation on the medicinal mushroom submerged fermentation. Such work is very helpful to other mushroom fermentations for useful metabolite production.

Photodegradation of seratrodast ([+/-]-7-(3,5,6-trimethyl-1,4-benzoquinone-2-yl)-7-phenyl-heptanoic acid, SD), a p-benzoquinone anti-asthmatic drug, has been investigated in different solutions. HPLC analysis showed that SD was degradated under UV irradiation at 254 nm to afford three major products (SD1, SD2 and SD3) in methanol and in acetonitrile/H2O solutions, while only two of them (SD2 and SD3) could be detected in acetonitrile solution. Furthermore, SD1 was unstable even when the samples were protected from light, so the acetylated SD1 (Ace-SD1) together with SD2 and SD3 were isolated by semi-preparative reversed-phase HPLC. The structures were elucidated as 6-(2,5-diacetoxy-3,4,6-trimethyl-phenyl)-7-phenyl-hept-6-enoic acid (Ace-SD1), 7-phenyl-6-(2,4,5-trimethyl-3,6-dioxo-cyclohexa-1,4-dienyl)-hept-6-enoic acid (SD2) and 5-(5-hydroxy-4,6,7-trimethyl-2-phenyl-benzofuran-3-yl)-pentanoic acid (SD3) based on the spectral data of MS, UV spectrum, IR spectrum and NMR spectrum. Meanwhile, a possible route for the formation of these photoproducts was proposed, which might explain the generation procedure of SD1, SD2 and SD3 during UV irradiation.

The purpose of this work was to develop a sensitive, selective, and validated stability-indicating high-performance liquid chromatographic (LC) assay of atorvastatin (ATV) in bulk drug and tablet form. ATV was subjected to different stress conditions, including UV light, oxidation, acid-base hydrolysis, and temperature. ATV and its degradation products were analyzed on an Agilent Zorbax XDB C18 column using isocratic elution with acetonitrile-0.02 M sodium acetate, pH 4.2 (45 + 55, v/v) for 25 min. The samples were monitored with fluorescence (FL) detection at 282 nm (excitation)/400 nm (emission). The response ratio of FL to UV detection (at 247 nm) for ATV was 1.66. The method showed good resolution of ATV from its decomposition products. The photodegradation products were separated by silica gel thin-layer chromatography using double development with ethyl acetate-n-hexane-glacial acetic acid-methanol (40 + 55 + 0.5 + 4.5, v/v/v/v) followed by (39 + 55 + 0.5 + 5.5, v/v/v/v), and confirmed by LC-FL analysis. The FL response was linear over the investigated range for ATV. The linear range was 10-1200 ng/injection, and the limit of quantitation was 2.0 ng/injection.