Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Chem Pharm Bull (Tokyo). 2024;72(10):913-916. doi: 10.1248/cpb.c24-00406.

Synthesis of Novel Pseudo-Enantiomeric Phase-Transfer Catalysts from Cinchona 
Alkaloids and Application to the Hydrolytic Dynamic Kinetic Resolution of 
Racemic 3-Phenyl-2-oxetanone.

Kawasaki M(1), Shirai T(2), Yatsuzuka K(1), Shirai R(1).

Author information:
(1)Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
(2)Graduate School of Biomedical and Health Sciences, Hiroshima University.

Naturally occurring Cinchona alkaloids such as quinidine (QD)/cinchonine (CN) 
and their diastereomers, quinine (QN)/cinchonidine (CD), have been recognized as 
pseudo-enantiomeric pairs. Utilizing these pseudo-enantiomeric alkaloids as 
chiral resources provides complementary enantioselectivity in many asymmetric 
reactions. During the screening of Cinchona alkaloid phase-transfer catalysts 
(PTCs) in the hydrolytic dynamic kinetic resolution of racemic 
3-phenyl-2-oxetanone (1) to tropic acid (2), we found that the introduction of a 
4-trifluoromethylphenyl group at the vinyl terminus of BnQN significantly 
reduced the enantioselectivity to 41% enantiomeric excess (ee). The optimized 
structure of tetrahedral intermediates (TI, PTC + 1 + OH-) of hydrolysis 
obtained by density functional theory (DFT) calculations shows that the 
orientation of the quinoline and benzene rings of QD class PTC are nearly 
parallel to each other and to construct a greatly extended π-electron cloud 
surface, allowing good π-π interaction with the benzene ring of 1.

DOI: 10.1248/cpb.c24-00406
PMID: 39462548 [Indexed for MEDLINE]


2. Sci Rep. 2024 Sep 18;14(1):21775. doi: 10.1038/s41598-024-71046-6.

"Eco-friendly HPLC method for analysis of dipyrone and hyoscine in different 
matrices with biomonitoring".

El Kalla RA(1), Ghoniem NS(2), Zaazaa HE(3), Gendy AEE(1), Sedik GA(3).

Author information:
(1)Analytical Chemistry Department, Faculty of Pharmacy, Misr International 
University, Km 28 Misr-Ismailia Road, Cairo, Egypt.
(2)Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Kasr El 
Aini, Cairo University, Cairo, 11562, Egypt. Nermine.ghoniem@pharma.cu.edu.eg.
(3)Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Kasr El 
Aini, Cairo University, Cairo, 11562, Egypt.

A selective, precise, and accurate reversed HPLC method has been developed and 
validated for simultaneous separation and determination of two veterinary drugs, 
dipyrone and hyoscine, in their combined dosage form in the presence of their 
official impurities, namely 4-aminoantipyrine and tropic acid, in addition to 
the formulated preservative: phenol. The linearity range was found to be 
(1.00-35.00 µg/mL) for dipyrone and (2.50-50.00 µg/mL) for hyoscine. It 
exhibited a satisfactory linearity regression R (0.9999) for both drugs with LOD 
0.22 µg/mL and 0.72 µg/mL and LOQ 0.65 µg/mL and 2.19 µg/mL for dipyrone and 
hyoscine, respectively. Additionally, the two cited drugs were also determined 
in the presence of dipyrone active metabolite 4-aminoantipyrine using diclofenac 
as an internal standard in bovine urine. The linearity range was found to be 
(15-75 µg/mL) for dipyrone, (2.5-60 µg/mL) for hyoscine, and (2.5-60 µg/mL) for 
4-aminoantipyrine with linearity regression R (0.9999-0.9998). The LLOQ (15, 
2.5, 2.5 µg/mL), LQC (45, 7.5, 7.5 µg/mL), MQC (55, 25, 25 µg/mL), and HQC (60, 
50 50 µg/mL) were determined for dipyrone, hyoscine and 4-aminoantipyrine, 
respectively. UV detection was carried out at 220 nm. The method was validated 
according to the ICH guidelines, as well as according to FDA guidelines for 
determining both drugs in bioanalytical matrices and both proved accuracy and 
precision. A statistical comparison was made between the results obtained and 
those obtained by the reported method, showing no significant difference in 
accuracy and precision at p = 0.05. The suggested method was proved eco-friendly 
through a greenness assessment using two different tools (The analytical 
eco-scale scored 83, and the AGREE-Analytical Greenness Metric approach scored 
0.83). The suggested method can be used in the routine work of quality control 
labs, screening for drug abuse, and ensuring clean sport for horse racing.

© 2024. The Author(s).

DOI: 10.1038/s41598-024-71046-6
PMCID: PMC11410794
PMID: 39294182 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.


3. Cont Lens Anterior Eye. 2024 Oct;47(5):102246. doi:
10.1016/j.clae.2024.102246.  Epub 2024 Jun 8.

Absorption and attachment of atropine to etafilcon A contact lenses.

Abdullah Aziz M(1), Kuppusamy R(2), Mazumder K(3), Hui A(4), Maulvi F(3), 
Stapleton F(3), Willcox M(3).

Author information:
(1)School of Optometry and Vision Science, University of New South Wales, 
Sydney, Australia. Electronic address: md_abdullah.aziz@unsw.edu.au.
(2)School of Optometry and Vision Science, University of New South Wales, 
Sydney, Australia; School of Chemistry, University of Sydney, Sydney, Australia.
(3)School of Optometry and Vision Science, University of New South Wales, 
Sydney, Australia.
(4)School of Optometry and Vision Science, University of New South Wales, 
Sydney, Australia; Centre for Ocular Research and Education, School of Optometry 
& Vision Science, University of Waterloo, Canada.

PURPOSE: Myopia (short-sightedness) is a growing vision problem worldwide. 
Currently atropine eye drops are used to control the progression of myopia but 
these suffer from potential lack of bioavailability and low ocular residence 
time. Commercially available myopia control contact lenses are also used to 
limit myopia progression, but neither atropine nor contact lenses individually 
completely stop progression. Development of myopia control contact lenses which 
could deliver therapeutic doses of atropine is thus desirable and may provide 
increased efficacy. This study was designed to explore the feasibility of 
attaching atropine to etafilcon A contact lenses through an esterification 
reaction.
METHODS: Carboxylic acid groups on etafilcon A contact lenses were quantified 
using Toluidine Blue O. The carboxylic acid groups in etafilcon A contact lenses 
were activated using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC-HCl) and 
N-hydroxysuccinimide (NHS) crosslinkers after which atropine was added to 
undergo potential binding via esterification. Atropine was released from lenses 
by alkaline hydrolysis. Reverse phase high performance liquid chromatography 
(HPLC) was used to detect and quantify the released atropine and its degradation 
products in solution. Contact lenses that had not been activated by EDC-NHS 
(controls) were also examined to determine the amount of atropine that could be 
absorbed rather than chemically bound to lenses.
RESULTS: Each etafilcon A contact lens contained 741.1 ± 5.5 µg carboxylic acid 
groups which may be available for esterification. HPLC had a limit of detection 
for atropine of 0.38 µg/mL and for tropic acid, an atropine degradation product, 
of 0.80 µg/mL. The limits of quantification were 1.16 µg/mL for atropine and 
2.41 µg/mL for tropic acid in NH4HCO3. The etafilcon A lenses adsorbed up to 
7.69 μg atropine when incubated in a 5 mg/mL atropine solution for 24 h. 
However, there was no evidence that atropine could be chemically linked to the 
lenses, as washing in a high concentration of NaCl removed all the atropine from 
the contact lenses with no atropine being subsequently released from the lenses 
after incubating in 0.01 N NH4HCO3.
CONCLUSIONS: Etafilcon A contact lenses contain free carboxylic acids which may 
be an appropriate option for attaching drugs such as atropine. Etafilcon A 
lenses adsorbed up to 7.69 μg atropine, which would be more than enough to 
deliver atropine to eyes to control myopia. However, atropine could not be 
chemically bound to the carboxylic acids of the etafilcon A lenses using this 
methodology.

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/j.clae.2024.102246
PMID: 38851947 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


4. Int J Pharm. 2024 Jul 20;660:124294. doi: 10.1016/j.ijpharm.2024.124294. Epub 
2024 May 31.

Enhanced ophthalmic bioavailability and stability of atropine sulfate via 
sustained release particles using polystyrene sulfonate resin.

Li F(1), Ye X(1), Li M(1), Nie Q(2), Wang H(3), Zhang G(4), Dong L(1), Wang 
C(2), Wu L(2), Liu H(5), Wang L(6), Peng C(7), Zhang J(8).

Author information:
(1)College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, 
China; Yangtze Delta Drug Advanced Research Institute, Nantong 226133, China; 
Jiangsu Yunshi Pharmaceutical Technology Co. Ltd., Nantong 226133, China.
(2)Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 
201210, China.
(3)Yangtze Delta Drug Advanced Research Institute, Nantong 226133, China; 
Jiangsu Yunshi Pharmaceutical Technology Co. Ltd., Nantong 226133, China.
(4)Jiangsu Yunshi Pharmaceutical Technology Co. Ltd., Nantong 226133, China.
(5)Jiangsu University, Zhenjiang 212000, China; Jiangsu Yunshi Pharmaceutical 
Technology Co. Ltd., Nantong 226133, China. Electronic address: 
hml19970522@163.com.
(6)Yangtze Delta Drug Advanced Research Institute, Nantong 226133, China. 
Electronic address: 22914692@qq.com.
(7)College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, 
China. Electronic address: pengcan@ahtcm.edu.cn.
(8)College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, 
China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 
Shanghai 201210, China; Yangtze Delta Drug Advanced Research Institute, Nantong 
226133, China; Jiangsu Yunshi Pharmaceutical Technology Co. Ltd., Nantong 
226133, China. Electronic address: jwzhang@simm.ac.cn.

Atropine sulfate (ATS) eye drops at low concentrations constitute a limited 
selection for myopia treatment, with challenges such as low ophthalmic 
bioavailability and inadequate stability. This study proposes a novel strategy 
by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) 
characterized by a spherical shape and uniform size for cationic exchange with 
ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum 
and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies 
demonstrated that ATS@SPSR suspension eye drops exhibited sustained release 
characteristics, and tropic acid, its degradation product, remained undetected 
for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New 
Zealand rabbits indicated a significant increase in mean residence time (MRT) 
and area under the drug concentration-time curve (AUC0-12h) for ATS@SPSR 
suspension eye drops compared to conventional ATS eye drops. Moreover, safety 
assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops 
in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR 
suspension eye drops enhanced the bioavailability and stability of ATS, offering 
a promising avenue for myopia treatment.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.ijpharm.2024.124294
PMID: 38823467 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


5. J Am Chem Soc. 2024 Mar 13;146(10):6604-6617. doi: 10.1021/jacs.3c12020. Epub 
2024 Mar 3.

Cobalt-Catalyzed Enantioselective Hydroboration of α-Substituted Acrylates.

Patil MD(1), Ghosh KK(1), RajanBabu TV(1).

Author information:
(1)Department of Chemistry and Biochemistry, The Ohio State University, 
Columbus, OH 43210, United States.

Even though metal-catalyzed enantioselective hydroborations of alkenes have 
attracted enormous attention, few preparatively useful reactions of α-alkyl 
acrylic acid derivatives are known, and most use rhodium catalysts. No examples 
of asymmetric hydroboration of the corresponding α-arylacrylic acid esters are 
known. In our continuing efforts to search for new applications of 
earth-abundant cobalt catalysts for broadly applicable organic transformations, 
we have identified 2-(2-diarylphosphinophenyl)oxazoline ligands and mild 
reaction conditions for efficient and highly regio- and enantioselective 
hydroboration of α-alkyl- and α-aryl- acrylates, giving β-borylated propionates. 
Since the C-B bonds in these compounds can be readily replaced by C-O, C-N, and 
C-C bonds, these intermediates could serve as valuable chiral synthons, some 
from feedstock carbon sources, for the synthesis of propionate-bearing motifs 
including polyketides and related molecules. Two-step syntheses of "Roche" ester 
from methyl methacrylate (79%; er 99:1), arguably the most widely used chiral 
fragment in polyketide synthesis, and tropic acid esters (∼80% yield; er ∼93:7), 
which are potential intermediates for several medicinally important classes of 
compounds, illustrate the power of the new methods. Mechanistic studies confirm 
the requirement of a cationic Co(I) species [(L)Co]+as the viable catalyst in 
these reactions and rule out the possibility of a [L]Co-H-initiated route, which 
has been well-established in related hydroborations of other classes of alkenes. 
A mechanism involving an oxidative migration of a boryl group to the β-carbon of 
an η4-coordinated acrylate-cobalt complex is proposed as a plausible route.

DOI: 10.1021/jacs.3c12020
PMCID: PMC11407689
PMID: 38431968

Conflict of interest statement: The authors declare no competing financial 
interest.