The genus Oxypetalum was classified to the Asclepiadaceaus family, and this family
was recently included in Apocynaceae. Oxypetalum
caeruleum is a plant indigenous to
South America and distributed as a garden
plant in Japan.
In the course of studying phytochemicals in Asclepiadaceaus plants,
authors investigated the constituents in O.
caeruleum. In this investigation, triterpenoids, pregnanes, one pregnane
glycoside, lignanes and lignane glycosides were afforded. Many kinds of
pregnanes and their glycosides are detected in the Apocynaceaus (including
Asclepiadaceaus) plants. The fact that O.
caeruleum only yielded pregnanes and their
glycosides still indicates that these compounds are characteristic of this
family.
Boronic acids are well-known as coupling partners
of Suzuki-Miyaura cross-coupling reaction, and also known as protecting reagents
of diols. In this note, two alkylated hydroquinone natural products,
violaceoids A and C, were synthesized by the protecting-group-free method
employing commercially available 2,5-dihydroxybenzaldehyde as the starting
material. The key step of the synthesis was the one-pot
protection/Suzuki–Miyaura cross-coupling of hydroquinone utilizing
alkenylboronic acid. This reaction enabled the protecting-group-free and
concise synthesis of violaceoid A. Furthermore, the conversion of violaceoid A
into violaceoid C was also described.
The extract of an Epipolasis sp. marine sponge collected
in the Republic of Palau provided four new pregnane 10,2 carbolactone
derivatives. The structures of these rare pregnane analogues were fully
elucidated through HRMS measurements and detailed analysis of their one- and
two-dimensional NMR spectroscopic data. Pregnane steroids possessing a
10,2-carbolactone ring have only been reported previously from Hawaiian
collections of Myrmekioderma and Petrosia (Stongylophora)
sponges, so the current results suggest this class of steroid is more widely
distributed in the marine environment than previously recognized.
The packing structure of intercellular lipids in the
stratum corneum plays a critical role in the skin’s barrier function. The
mechanism of packing structure disruption is not fully understood. The authors constructed
models for collapsed skin intercellular lipids composed of short-chain free
fatty acids and α-hydroxy
ceramide. To investigate the packing structure’s characteristics, they changed the
lipid composition and used temperature-scanning, simultaneous small-angle and
wide-angle X-ray diffraction to determine resulting structural changes. The results suggest a change in ceramide
conformation into a V-shape structure. The authors discussed the relationship
between the V-shape structure formation and a reduction in the skin’s barrier
function.
Authors evaluate the characteristics of
acid-activated bentonite by focusing on its capability of improving the quality
of tap water used during wire electrical discharge machining. This study shows
that the acid activation of bentonite using sulfuric acid, nitric acid, and
phosphoric acid solutions increases the specific surface area and pore volume. Additionally,
authors revealed that the relationship between the concentrations of the
removed ions and electrical conductivity were negatively correlated (correlation
coefficient: -0.950). Thus, the acid-activated bentonite is useful in
controlling the reduction in the electrical conductivity of tap water.
Quantitative
NMR (qNMR) has emerged
as a new absolute
quantitation method for
small molecules. Authors examined the absolute purity determination of a hygroscopic substance
indocyanine green (ICG)
using qNMR. The three different humidity conditions yielded comparable purity
means of 86.12 ± 2.70%, 84.19 ± 0.47%, and 82.26 ± 0.19%
under non-controlled humidity, controlled humidity using a saturated NaBr
solution, and using a constant temperature and humidity box, respectively. As
the results using the constant temperature and humidity box showed the lowest
variability, it is recommended to use it if the reference standard of ICG with
its purity value is needed for Japanese Pharmacopoeia assays.
Stereoselectivity
in chemical glycosylation frequently varies in reaction substrates. This paper
describes the influence of the protecting groups on rhamnose connected to the
2-O position of a glucosyl donor with axial-rich conformation on stereoselectivity
in its glycosylation with cholestanol. The authors revealed that two bulky
silyl groups existing at the 3-O and 4-O positions of rhamnose synergistically
enhanced β-selectivity. In contrast, the silyl group introduced to the 2-O
position decreased the selectivity. These results suggest that appropriately designing
a protecting-group pattern for another sugar far from the reaction center of a
glycosyl donor can control the stereoselectivity of glycosylation.
Tubulin is an important target for developing anticancer drugs. To
discover novel tubulin polymerization inhibitors, the authors designed and
synthesized a new series of pyrimidine-based compounds based on the principle
of molecular hybrid-based approach. Several compounds exhibited potent
anti-tubulin activity and showed antiproliferative activities against MCF-7 and
HepG2 cancer cell lines. The results indicated that these compounds may have
the potential for further development as anticancer agents.
Intramolecular Diels-Alder (IMDA) reactions are powerful
synthetic methods for construction of complex carbon skeletons from relatively
simple starting materials. Regioselectivity
for producing fused or bridged products by the IMDA reactions is very important
for planning a rational synthetic route for target molecules. It has been well known that the IMDA
reactions usually provide fused products, while factors for selective formation
of bridged products has not been understood well. The authors experimentally found some factors
for giving bridged products selectively in IMAD reactions, and they explained
the reasons for the observed bridged selectivity by DFT calculations.
Stimulus-responsive
molecules that modify nucleic acids in a site- and base-selective manner play
an important role for genomic research. N-Acetyl-7-nitroindoline is a characteristic in
that its acetyl group is photo-activated to acetylate amines to form amides. In
this study, the N-acetyl-7-nitroindoline
part was connected to the 2´-deoxyribose part, which was incorporated into the oligodeoxynucleotide
probes, and their photo-reactivities toward the complementary RNA were
investigated. One probe was photo-activated to deacetylate to the nitroso
derivative. Photo-activation of another probe induced acetylation of the RNA. An
interesting finding was the cross-link formation of another probe with the RNA strand.
Nitrogen dioxide has been used
as an oxidant and nitrating reagent in organic synthesis. However, its use is
limited because it is harmful and hard to handle. Iron(III) nitrate nonahydrate
has attracted attention as a source of nitrogen dioxide because it is a readily
available reagent of low toxicity and cost. This paper describes development of
nitrolactonization mediated by iron nitrate as a source of nitrogen dioxide. Nitrolactones
obtained by this reaction could lead to useful compounds, such as
1,2-aminoalcohol and amino acid derivatives bearing a tetrasubstituted carbon
center.
Peptide/protein thioesters function as an
indispensable synthetic intermediate in Native Chemical Ligation (NCL) that has
enjoyed great success in the chemical synthesis of proteins. Facile conversion
of recombinant proteins to thioesters allows for the straightforward access to
semi-synthetic proteins with chemically synthesized peptides used as an NCL
partner. In this paper, the authors developed an efficient thioester-producing
protocol. The protocol features the traceless conversion of the CysPro triple
repeat–Leu-OH-tagged sequence to the corresponding thioesters by treatment with
carboxypeptidase Y in the presence of hydrazine followed by an auto-processing
of the CysPro units.
Molecular imprinting has been broadly perceived as the most advanced
technology for preparing various materials that have a specific recognition
site with selective adsorption. MIPs (Molecular Imprinted Polymer) are
three-dimensional polymers with specific recognition sites for a certain
molecule. A MIP is formed by crosslinking template with monomers to create
copolymers. For every MIP, each template:monomer:crosslinker ratio shows a distinct
performance for a specific analyte. Ratio effect on analytical performances are
briefly outlined in this review. From all reports in this review, the synthesis
of MIP using a template:monomer:crosslinker ratio of 1:4:20 is more likely to
provide optimal imprinting efficiency.
With
the globalization of the drug supply chain, the quality assurance of drugs is
required worldwide. Pharmacopoeias provide public standards for the drug quality
assurance, and smooth incorporation of the concepts of the international
guidelines into pharmacopoeias is desired. In particular, impurities in drugs
are to be controlled to ensure patient safety. The authors focused on the
harmonized guidelines for residual solvents, elemental impurities, and
mutagenic impurities, and proposed an approach for promoting incorporation of
the concepts of the guidelines into pharmacopoeias by combining the cause and
effect analysis and the logic model.
In
clinical practice, a thickening solution is frequently used to allow easy
swallowing of tablets as well as foods by patients suffering from dysphagia. This
study
investigated the effect of thickening solution on tablet disintegration. Model tablets
containing different disintegrants were prepared and their disintegration times
were measured. The tablet disintegration times were
significantly prolonged by immersion in thickening
solution containing xanthan gum and the degree of prolongation differed depending on
the type of disintegrant
contained in the tablets. These findings provide valuable information for
design of tablet formulation and clinical medication
management for older patients with dysphagia.
Chlorofluoroacetamide (CFA) shows
chemically tuned mild reactivity that is suitable as an electrophilic warhead
for highly target selective covalent inhibitors. Assembly of a small set of
CFA-appended fragment library and its screening against cysteine protease
papain demonstrated the potential utility of CFA in novel covalent drug
discovery using a fragment-based approach.
This
review describes development of innovative reactions utilizing the
characteristic reactivity of oxygen atoms, 1) asymmetric synthesis of chiral quaternary
carbon centers, 2) asymmetric synthesis using acetal functions, and 3) organic
chemistry using acetal-type reactive salt chemical species, and their
application to the asymmetric synthesis of natural products such as
Fredericamycin A, anthracycline antibiotics, scyphostatin, Sch 642305, stenin, claboronin,
rubrenolide, rubrynolide, centrolobine, and decytospolides A and B, etc. In
particular, reactions using acetal-type reactive salt chemical species can
alter the retrosynthesis planned based on conventional reactions because they allow
the coexistence of functional groups that normally cannot coexist.
Binding
assays are widely used to study the estrogenic activity of endocrine-disrupting
chemicals targeting the estrogen receptor (ER). In this study, the authors synthesized benzofurazan-labeled estradiol
(BD-E2) derivatives as a fluorescent ligand for ER binding assays. BD-E2
compounds exhibit spectroscopic properties with high fluorescence intensities
and large Stokes shifts in a hydrophobic environment. Analysis of the fluorescent
ligands and human recombinant ER interactions revealed that the fluorescence
intensity increased in hydrophobic environments, such as the receptor-binding
site. By evaluation of the bound ligands based on changes in the fluorescence
intensity, the authors established a simple,
rapid, reliable ER binding assay.
An extemporaneous preparation, sodium
dantrolene granules, has been manufactured using planetary centrifugal
granulation method in the pharmacy. The amount of water was determined based on
plastic limit value of the formulation, which is a critical parameter of the
granulation method. The granulation process completes within 45 s, followed by
coating process (20 s). The resultant granules show sharp particle size
distribution and excellent flowability. The bulky powder was reformulated to the
granules with non-adhesive and free-flowing properties. Thus, the granulation
improves the usability of the medicine in the dispensing and dosing processes.
The quaternary nitrogen (N-Q) has been found to be
an effective adsorption site for nitrate ions. However, in addition to N-Q, there
are many functional groups such as C-π sites on activated carbon fibers (ACFs),
and these functional groups have various effects on the adsorption capacity. Understanding
the properties of functional groups other than N-Q can be expected to further
improve ACFs adsorption performance. In this paper, the authors prepared the ACFs
with and without N-Q and examined their adsorption properties.