Codeine, is used worldwide and abused as a recreational drug. The authors developed a system to selectively and sensitively detect codeine from over-the-counter medications containing interfering drug components by electrochemiluminescence (ECL) combined with potential modulated technique (PM). The sensitivity for detection of codeine by PM-ECL was more than one order of magnitude larger than that obtained in conventional potential sweep mode. The established technique was applied to codeine determination in over-the-counter drugs and medicines and was not affected by the presence of structurally similar chemicals. The proposed method expected to apply as a sensitive on-site analytical method for a wide range of detection, especially clinical and forensic analysis.
Reliable data on the compatibility and chemoselectivity of functional groups are essential for assessing the usefulness of chemical reactions. Authors systematically evaluated the functional group tolerance of carbene-mediated reactions as a core project of the Grant-in-Aid for Transformative Research Area A “Digitalization-driven Transformative Organic Synthesis”. In the course of this study, unexpected C-H functionalization of a naphthol derivative used as an additive was observed. Authors believe that collecting dependable information, including negative experimental results, plays a crucial role in developing organic synthesis.
Photolabile protecting groups (PPGs) have been utilized in many research fields such as organic synthesis and chemical biology because their fast and selective photocleavage proceeds under mild conditions. The authors previously reported the design and synthesis of 8-azacoumarin-type PPGs based on the alkene-to-amide replacement of the 6-bromo-7-hydroxy-coumarin-4-ylmethyl (Bhc) group. The characteristic feature of these PPGs is their aqueous solubility, which is remarkably higher than that of Bhc. The authors found that 8-azacoumarin-type PPGs can also be used as two-photon excitation sources because the photolytic efficiency for two-photon excitation showed preferable physicochemical values for applications in cells and tissues.
[Highlighted Paper selected
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The authors investigated the use of electrospun
polyvinyl alcohol (PVA) nanofibers for the drug delivery of lysozyme (LZM),
focusing on how different PVA grades affect drug release characteristics. PVA
nanofibers with a 50% LZM content achieved efficient encapsulation and quick
release within 30 minutes. Using fully hydrolyzed PVA led to more controlled
release due to its reduced water solubility. Notably, the study highlighted
coaxial electrospinning to create PVA/LZM nanofibers coated with
polycaprolactone, facilitating extended drug release. This approach clarified
the relationship between the characteristics of PVA in nanofibers and drug
release properties, offering promising insights for pharmaceutical nanofibers.
Indole is a crucial heterocycle found in various biologically active natural products and medicinal compounds. Therefore, developing convenient methodologies for modifying the indole structure is an interesting topic for the discovery of pharmaceuticals and functional materials. In this context, the authors report trifluoromethanesulfonic acid (2.1 equiv) efficiently facilitates the 1,2-migration reaction of the substituent from C3- to C2- position of the indole structure. Alkyl, aryl groups such as benzyl, isopropyl, phenyl were tolerated for this reaction (up to 98% yield).
Vizantin is a TLR-4 antagonist developed in the author's laboratory. In this article, to improve the water solubility of vizantin, the authors designed a new vizantin derivative in which all hydroxyl groups of the sugar unit were sulfated. It has been confirmed that the synthesized vizantin derivative spontaneously forms string-like micelles and dissolves in water. The authors also report that string-like micelles of more uniform size are formed in physiological saline than in distilled water, making it possible to prepare an ideal injection solution.
Heterogeneous catalysis has gained increasing interest in the growing demand of sustainable manufacturing of pharmaceutically relevant compounds. The authors report herein a mesoporous silica-supported oxovanadium (V-MPS4)-catalyzed nucleophilic removal of the p-methoxybenzyl (PMB) protective group on alcohols under mild and redox-neutral conditions. The method has a wide reaction scope, including primary, secondary, and tertiary alcohols with various functional groups. The catalyst was reused six times without a significant loss in the conversion. The advantages of using the heterogeneous catalyst were further demonstrated by conducting the deprotection reaction in a flow process, which showed significantly higher turnover frequency compared to the batch reactions.
The guaianolide sesquiterpene lactone cynaropicrin and its derivatives showed antiproliferative activity against human glioblastoma U-251 MG cells and their cancer stem cells. Accordingly, the authors synthesized several derivatives of cynaropicrin and investigated their structure-activity relationships. The authors conclude that the α-methylene-γ-butyrolactone moiety involved in the Michael addition reaction and the 5,7,5-ring are both important for antiproliferative activities. The results of this study suggest guaianolide sesquiterpene lactones are useful for developing anticancer drugs targeting glioblastoma.
[Highlighted Paper selected
by Editor-in-Chief]
Catalytic hypervalent iodine oxidation
reactions have recently attracted
attention to as an environmentally benign and safe method. The authors now
report the first lactam-type 2-iodobenzamide catalysts, 8-iodoisoquinolinones (IB-lactams), that can act as a
catalyst at room temperature for the oxidation of alcohols with Oxone (2KHSO5·KHSO4·K2SO4) and show the highest reactivity among their
previously reported ones. They have a conformationally rigid 6/6 bicyclic
lactam structure. The lactam structure could form an efficient intramolecular I---O interaction in its hypervalent
species. The interaction could stabilize them to achieve rapid oxidation to
pentavalent iodine species, which can oxidize alcohols to carbonyl compounds.
The authors focus on the long-term
consistency of dissolution profiles of generic pharmaceutical products. By
analyzing a vast dataset of 1675 products across 127 ingredients, the study
uncovers the intricate factors influencing changes in dissolution profiles
post-approval. It emphasizes the significance of co-development in the increase
of dissimilar dissolution products, the pivotal role of API particle size in poorly
soluble drugs, and the impact of acidic or basic residues on dissolution changes
at specific pH levels. These findings highlight the necessity for proper
development that consider formulation and process variables to ensure the
sustained bioequivalence of generic drugs.
[Highlighted Paper selected by Editor-in-Chief]
Kopsiyunnanine B was isolated from Yunnan Kopsia arborea and
possesses a unique folded and complex pentacyclic structure containing six
contiguous chiral centers. In this article, the authors reported the asymmetric
total synthesis of Kopsiyunnanine B, along with their originally proposed
biosynthetic pathway. The key transformation is an impressive cascade reaction
that constructs three ring structures and three chiral centers in one step.
Following the stereoselective reduction of the β-acrylate and oxidation to
oxindole, the natural product is synthesized over 14 steps. Their careful
consideration of the biosynthetic hypothesis has resulted in an exceptionally
efficient synthesis with a minimal number of steps.
Given
the spread of antimicrobial-resistant bacteria (AMR), there is an urgent need
for the ongoing search for novel antibacterial natural products. The authors discovered
five new viridogrisein congeners from Streptomyces niveoruber with potent
antibacterial activities against Gram-positive bacteria. Additionally,
co-treatment with griseoviridin, another natural product from the same producer,
enhanced the activity. Biosynthetic studies have revealed that SgvY, encoded in
the viridogrisein biosynthetic gene cluster, detoxifies viridogrisein against Staphylococcus
aureus by linearization, suggesting its role in the self-resistance system
in S. niveoruber. These results could facilitate the understanding of antimicrobial-resistant
mechanism for developing the countermeasures against AMR.
The
Kawakita equation has been used for estimating yield pressure and porosity of
compressed powder in the die. This equation assumes the compression pressure is
homogeneously distributed. However, in actual powders, it is not homogeneously
distributed due to the friction on the die wall. The authors extended the
Kawakita equation by accounting for the inhomogeneous distribution of
compression pressure. The extended Kawakita equation theoretically explained
the powder behavior yielding sequentially from the loading punch to fixed punch
due to the spatial limitation of particle rearrangement. Therefore, the
extended Kawakita equation advances understanding of powder compaction in die.
While the addition of cellulose
nanofiber (CNF) to tablet formulations during direct compression has attracted
increasing attention as a means for enhancing tablet strength and
disintegration, they are also known to increase the variation in tablet weight
and drug content. This study evaluated the effect of pulverized CNF on the
variation in tablet weight and drug content. The pulverized CNF reduced both
weight and drug content variation to a larger extent than untreated CNF.
Further, either CNF achieved sufficient tablet strength and short
disintegration time. Thus, the authors provided evidence that CNF is useful as
a multifunctional additive.
Computational
screening is a powerful technique for drug discovery today. In this work, a virtual
screening was performed to find SARS-Cov-2 PL protease inhibitors, utilizing a
chemical database consisting of approved and investigational drugs. A key issue
for successful virtual screening is the accuracy of computational predictions
for the binding pose and score of each compound to the target. The authors
applied their original software program, Chem. Pharm. Bull., 2017, 65, 461, for
calculating the score. Their approach identified five inhibitory compounds
against the PL protease. The inhibitory activities were evaluated by an
enzymatic assay with the FRET technique.
Exosomes, a kind of extracellular vesicles,
have actively been researched as the drug delivery system (DDS) for nucleic
acid drugs. The authors previously reported exosome-hijacking
antibody-oligonucleotide conjugate “ExomiR-Tracker”, which is consisting of
cationic oligoarginine linker-introduced anti-exosome antibody (anti-Exo) and
nucleic acid drugs.
In this article, it was revealed that the
intracellular delivery capability of nucleic acid drugs and the functional
inhibition of target gene in lung adenocarcinoma cells was significantly
improved by branched oligoarginine adapted ExomiR-Tracker (Branch
ExomiR-Tracker) as compared to conventional one. Their findings demonstrate the
promising potential of ExomiR-Tracker as a tool for delivering nucleic acid
drugs and provide novel insights into the exosome-hijacking DDS.
This study utilized low-field time-domain NMR
(TD-NMR) to ascertain the solid active pharmaceutical ingredient (API) content
in suspension-type pharmaceutical oral jellies. The authors prepared and tested
jellies containing various APIs, such as acetaminophen (APAP), indomethacin
(IMC), and L-valine. The authors determined that precise API content
measurement in jellies was achieved by utilizing NMR signal intensity measured
through the solid-echo pulse sequence. Additionally, the authors observed that
smaller API particle sizes resulted in faster T2 relaxation rates. In summary,
TD-NMR proves to be a robust tool for evaluating the dispersion state of API
powders in pharmaceutical oral jellies.
To enhance the structural diversity in aryne-based products, the aryne precursors bearing various functional groups have been continuously
developed. However, the use of unsymmetrically substituted
arynes is frequency constrained by the low regioselectivity.
Authors achieved
the regiocontrol by introducing
a fluoro-substituent in unsymmetrically 3,6-disubstituted arynes as a directing group. Particularly, the use of 3,6-disubstituted aryne having fluorine and bromine atoms led
to the good degree of regiocontrol in several reactions. These results consist with aryne distortion models reported by Garg and
Houk’s group.
A chiral lithium binaphtholate
base catalyst effectively mediates the asymmetric Michael addition of ketones
to less reactive acrylamides in a highly enantioselective manner. A small
excess of lithium tert-butoxide relative to the binaphthol is used to
facilitate the enolization of the ketone, thereby improving conversion of the
asymmetric Michael reaction. Computational studies support that the 3- and
3'-phenyl groups of the binaphtholate catalyst control the orientation of the
lithium enolate and the subsequent approach of acrylamide to achieve high
enantioselectivity.
This
study evaluated the effects of different forms of granulated lactose (GL) on
the physical properties of tablets and the effect of magnesium stearate on each
type of GL. The different forms of GL such as agitated granulation (GL-AG),
spray-dried granulation (GL-SD), and fluidized bed granulation (GL-FB) were
added as excipients during direct powder compression. When tablets with the
same blending conditions were compared, the tensile strength and disintegration
time followed the order as GL-FB > GL-SD > GL-AG. The authors presented
selection criteria for the suitability of different forms of GL during
tableting by examining the relevance between the type of GL and properties of
the tablets produced.