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Chemistry and Pharmacology of Naturally Occurring Flavoalkaloids
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Rashmi Gaur, Jyoti Gaur, Nikhilesh Kumar
(-)-licorice glycoside E was the first indole flavoalkaloid identified (51), in 1997, from the roots of Glycyrrhiza uralensis Fisch, commonly known as Tohoku licorice (Figure 21.2) (Hatano et al., 1998). The absolute configuration of 51 was determined with the help of CD spectra. Hubner et al. (1999) isolated the oxindole-flavoalkaloid (52) from the seeds of the horse chestnut Aesculus hippocastanum L. (Figure 21.2). The presence of sugar moieties was confirmed by acid-hydrolysis, semi-synthesis of its derivatives and gas chromatography. Kapusta et al. (2007) isolated from the same plant, and an ion consistent with the deoxy analog 53 was analyzed using mass spectrometry (Figure 21.2) (Kapusta et al., 2007).
Transport of Radiolabeled Enzymes
Published in Lelio G. Colombetti, Biological Transport of Radiotracers, 2020
The discussion here will be limited to the fundamentals concerning the structure and the radiolabeling of enzymes. Because the absolute configuration of enzymes and their stereochemistry are known from their amino acid sequences, the possibility of radio-labeling enzymes can be predicted. These amino acid sequences can be determined for low molecular weight enzymes, such as ribonuclease, muramidase, papain, and bromelain, by using an autoanalyzer. Results for 13 glucose-6-phosphate dehydrogenases have been reported by Levy.88 The absolute configuration of enzymes may be obtained by a comparison with the absolute configuration of the same enzyme synthesized from crystalline amino acids. This was foreseen in 1974 by Colombetti,89 who stated — concerning pancreatic enzymes — that “labeled amino acids will be used during synthesis and will be incorporated into the new enzymes being produced.”
Amphetamines and Related Stimulants: Some Introductory Remarks
Published in John Caldwell, S. Joseph Mulé, Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
The absolute configuration of these chiral centers has been established, and the greatest biological potency is obtained with the substituents around the carbon bearing the nitrogen in the S configuration, and these are generally dextrorotatory, i.e., (+) or d-isomers. For those compounds with two asymmetric centers, the most active stereoisomers are those with the IR, 2S configuration, and these are lavorotatory, i.e., (−) or I-isomers. The R configuration of these compounds around the carbon bearing the side chain hydroxyl group is the same as is found in biosynthetic noradrenaline and adrenaline. A fuller discussion of these matters is given by Ferris et al.16 and the possible isomers of amphetamine and ephedrine are illustrated in Figures 6 and 7. The two possible stereoisomers of amphetamine.The four possible stereoisomers of ephedrine.
Design, synthesis and in vitro biological studies of novel triazoles with potent and broad-spectrum antifungal activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Junhe Bao, Yumeng Hao, Tingjunhong Ni, Ruina Wang, Jiacun Liu, Xiaochen Chi, Ting Wang, Shichong Yu, Yongsheng Jin, Lan Yan, Xiaomei Li, Dazhi Zhang, Fei Xie
According to Scheme 1, twenty-seven novel triazole derivatives were synthesised. The key intermediate (2 R,3R)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butane-2,3-diol (1) was prepared as in our previous work9. In the next step, triazolyl-diol 1 was converted into methane sulphonate and then eliminated to give epoxide 2. Epoxide 2 was reacted with NaN3 to form ring-opening azide compound 3. Next, 3 was subjected to catalytic hydrogenation to afford amine compound 4, which was followed by a condensation reaction with various commercially available substituted propionic acids to obtain target compounds A1-A27. The chiral structure of key intermediates amine 4 was clearly confirmed by X-ray crystallographic analysis. The atom labelling and thermal ellipsoids of amine 4 are shown in Figure 3. It crystallised in the orthorhombic crystal system and P212121 space group with a = 8.9511(3) Å, b = 10.4014(4) Å, c = 13.8084(4) Å, α = 90°, β = 90° and δ = 90° (Table S1 in the supplementary material). Based on the results, the absolute configuration at C-2 and C-3 in amine 4 was determined to be R. All the newly synthesised compounds were characterised and confirmed by 1H NMR, 13C NMR, and LC-MS as described in Supporting Information.
A patent review of MAT2a inhibitors (2018–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Stephen J. Atkinson, Laura Evans, James S. Scott
In December 2021, a further quartet of patent applications from Ideaya Biosciences were published that further elaborated on this chemotype (Figure 8). The first [24] contained 70 examples with the same core as described above but with a 5-membered heteroaromatic ring, most commonly imidazole, attached via a carbon to the core N as exemplified by example 1.047 (17). In terms of core substituents, dimethyl was the most commonly featured amino-substituent with other alkyl amines and 4 and 5 membered rings also being exemplified. Trifluoromethyl was the most common substituent on the bicyclic aryl ring although the four most potent examples (<10 nM) had either chloro- or bromo- in this position. Additionally, substitution at the benzylic position, most typically with methyl, was present in more than half the examples with some being separated into their constituent enantiomers. These features are all represented in example 1.047 although it should be stated that the absolute configuration was arbitrarily assigned and not determined. The second [25] described a related core with a bridgehead nitrogen and contained 11 examples and an additional 27 prophetic ones. Example 1.001 (18) is representative of the equity contained within, containing an unsubstituted amino, trifluoromethyl substituent and unsubstituted phenyl ring which were the most commonly exemplified groups in each position.
Aminobenzisoxazole compounds as agonists of α7 nicotinic acetylcholine receptors: a patent evaluation (WO 2017027600)
Published in Expert Opinion on Therapeutic Patents, 2018
The synthesis of two key intermediates (R)-A-4 and B-3 were also shown in Figure 5. BH3 protection of commercially available quinuclidin-3-one and methylation with CH3I in the presence of NaH gave rise to A-2. Cleavage of the BH3 group in 20% TFA/DCM system overnight generated ketone A-5. Treatment of A-5 with (R)-1-phenylethanamine gave the corresponding oxime (R)-A-6. Reduction of (R)-A-6 with NaBH4 afforded a mixture of diastereomers favoring the desired (R, R)-A-7. Then salt formation of the diastereomers with 1 equiv fumaric acid followed by crystallization in methanol/ethyl acetate system allowed clean isolation of (R, R)-A-7 monofumarate. The absolute configuration of A-7 was unambiguously established as (R, R) by single crystal diffraction and power diffraction assays. Finally, hydrogenolysis of (R, R)-A-7 catalyzed by Pd/C generated (R)-A-4. Compound (S)-A-4 could be prepared in a similar fashion as the procedure for synthesizing compound (R)-A-4. Another key intermediate B-3 could be obtained by coupling 4-chloro-2-fluorobenzaldehyde with hydroxylamine to give the corresponding oxime B-2 followed by chlorination with NCS.