Directed Hydrogenation of Acyclic Homoallylic Alcohols: Enantioselective Syntheses of (+)- and (−)-Laurenditerpenol

Laurenditerpenol is the first marine natural product shown to inhibit hypoxia-inducible factor 1 (HIF-1) activation. Preclinical studies support that the inhibition of HIF-1 is one of the molecular targets for antitumor drug discovery. The synthetically challenging molecular architecture of laurenditerpenol, its absolute stereostructure, and the biological activity of several diastereoisomers were accomplished by our group in 2007 by diastereoselective synthesis. Herein, we report enantioselective syntheses of both enantiomers of laurenditerpenol involving sequential Michael addition and remote homoallylic hydroxyl group-directed asymmetric hydrogenation at ambient temperature and pressure as key reaction steps. The current approach is elegant and overall more efficient than the ones previously reported in the literature

Alternative Testing Methods for Skin Sensitization: NMR Spectroscopy for Probing the Reactivity and Classification of Potential Skin Sensitizers

Evaluating consumer products for potentially harmful side effects of chemical ingredients is important for the protection of both the consumer and those involved in the manufacturing process. In order to assess the risk potential of chemicals, regulatory agencies have encouraged the development of several <i>in silico</i>, <i>in vitro</i>, and <i>in chemico</i> methods as alternatives to eliminate or minimize the use of animals. To add structural information to the existing <i>in chemico</i> methods, an NMR-based method is proposed for probing the reactivity and classification of the potential electrophiles (E) using a model thiol, DCYA, as a nucleophile. The major advantage of the NMR method is the quantitation of the actual adduct, DCYA-E. The degree of reaction is here provided as a direct measurement of adduct formation and/or electrophile depletion, in contrast to other <i>in chemico</i> assays, e.g., ADRA and DPRA, where the reactivity is inferred from the quantification of the test nucleophile depletion. Moreover, the developed NMR method should serve as a qualitative and quantitative tool in understanding the site of reaction and other structural information associated with test sensitizer. This is particularly valuable and advantageous over methods encouraged by regulatory agencies, which merely provide quantification of the reaction but lack any structural information. Several compounds with multiple reaction sites were successfully tested with the proposed NMR method. Otherwise, these compounds have proven to be a challenge to identify and classify using existing alternative methods

A new isoflavane-4-ol derivative from <i>Melilotus officinalis</i> (L.) Pall.

<p>A new isoflavane derivative, melilofficinaside together with seven other metabolites including coumarin, uridine, methyl-<i>α</i>-d-fructofuranoside, and flavonoid glucosides were isolated from the aerial parts of <i>Melilotus officinalis</i> (L.) Pall.</p

Inhibition of CYP3A4 and CYP1A2 by <i>Aegle marmelos</i> and its constituents

<p>1. <i>Aegle marmelos</i> (bael) is a popular tree in India and other Southeast Asian countries. The fruit is usually consumed as dried, fresh or juice, and is reported to have a high nutritional value and many perceived health benefits. Despite its edible nature and therapeutic properties, no studies are reported regarding its effects on major drug metabolizing enzymes.</p> <p>2. This study was aimed to evaluate the inhibitory potential of methanolic extract of <i>A. marmelos</i> fruit and its constituents (three furanocoumarins, namely marmelosin, marmesinin and 8-hydroxypsoralen, and 1 alkaloid, aegeline) towards major Cytochrome P450 enzymes (CYP3A4, 2D6, 1A2, 2C9 and 2C19) using human liver microsomes and recombinant CYPs.</p> <p>3. The methanolic extract and marmelosin was found to be competitive and time-dependant inhibitor of CYP3A4. While reversible and non-competitive inhibition was observed for CYP1A2. Time-dependent inhibition of CYP3A4 was not affected by the addition of reduced glutathione. Marmesinin showed moderate inhibition of CYP3A4 and 1A2, while aegeline was a very weak inhibitor of CYP3A4 and showed no inhibition for CYP1A2 isoform. No significant inhibition of recombinant CYP2D6, 2C9, and 2C19 was seen with the extract or its constituents.</p> <p>4. This is the first report of CYP3A4 and CYP1A2 inhibition by <i>A. marmelos</i> extract and one of its furanocoumarins, marmelosin. Further studies are warranted to determine if acute or prolonged use of bael fruit could affect the pharmacokinetics of drugs that are substrates of CYP3A4 or CYP1A2.</p

<i>In Chemico</i> Evaluation of Tea Tree Essential Oils as Skin Sensitizers: Impact of the Chemical Composition on Aging and Generation of Reactive Species

Tea tree oil (TTO) is an essential oil obtained from the leaves of <i>Melaleuca alternifolia</i>, <i>M. linariifolia</i>, or <i>M. dissitiflora</i>. Because of the commercial importance of TTO, substitution or adulteration with other tea tree species (such as cajeput, niaouli, manuka, or kanuka oils) is common and may pose significant risks along with perceived health benefits. The distinctive nature, qualitative and quantitative compositional variation of these oils, is responsible for the various pharmacological as well as adverse effects. Authentic TTOs (especially aged ones) have been identified as potential skin sensitizers, while reports of adverse allergic reactions to the other tea trees essential oils are less frequent. Chemical sensitizers are usually electrophilic compounds, and <i>in chemico</i> methods have been developed to identify skin allergens in terms of their ability to bind to biological nucleophiles. However, little information is available on the assessment of sensitization potential of mixtures, such as essential oils, due to their complexity. In the present study, 10 “tea tree” oils and six major TTO constituents have been investigated for their sensitization potential using a fluorescence <i>in chemico</i> method. The reactivity of authentic TTOs was found to correlate with the age of the oils, while the majority of nonauthentic TTOs were less reactive, even after aging. Further thio-trapping experiments with DCYA and characterization by UHPLC-DAD-MS led to the identification of several possible DCYA-adducts which can be used to deduce the structure of the candidate reactive species. The major TTO components, terpinolene, α-terpinene, and terpinene-4-ol, were unstable under accelerated aging conditions, which led to the formation of several DCYA-adducts

Production of High Levels of Chirally Pure d‑2,3-Butanediol with a Newly Isolated <i>Bacillus</i> Strain

2,3-Butanediol (2,3-BD), especially when it exists in the chirally pure form, is a valuable chemical feedstock with numerous applications in various industries. However, in most cases, the 2,3-BD naturally produced by the microorganism is a mixture of two of the three isomers (d-2,3-BD, l-2,3-BD, and <i>meso</i>-2,3-BD), which has restricted applications and thus a much lower value than the chirally pure one. In this study, we report a new isolate <i>Bacillus spp.</i> FJ-4 strain, which can produce highly chirally pure d-2,3-BD (>99.9%) to high levels, with very high productivity and yield. The composition of the fermentation medium for the strain was sequentially optimized using statistical experimental methodologies. During a fed-batch experiment, 100.0 g/L of d-2,3-BD was produced from 226.8 g/L glucose, with a yield of 0.44 g/g (88.2% of the theoretical maximum). Acetoin was the primary byproduct, and no other byproduct such as lactate, acetate, or ethanol was detected, which would be advantageous for the downstream purification process. Moreover, no special conditions such as limited oxygen level (which generally limits the cell growth and thus final d-2,3-BD production) are required for the fermentation. These results indicated that <i>Bacillus spp.</i> FJ-4 is a robust workhorse for efficient d-2,3-BD production from low-value carbon sources

Hydroxylated Bisabolol Oxides: Evidence for Secondary Oxidative Metabolism in <i>Matricaria chamomilla</i>

German chamomile (<i>Matricaria chamomilla</i>) is one of the most popular medicinal plants used in Western herbal medicine. Among the various phytochemicals present in the essential oil of the flowers of German chamomile, bisabolol and its oxidized metabolites are considered as marker compounds for distinguishing different chemotypes. These compounds are influential in mediating the aroma of the essential oil of <i>M. chamomilla</i> and contribute to the therapeutic properties (anti-inflammatory, antibacterial, insecticidal, and antiulcer) of this species. In order to find other possible bisabolol derivatives as marker compounds for authentication of German chamomile in botanical and commercial products, an in-depth investigation using a GC-assisted fractionation procedure was performed on nonpolar fractions. As a result of this approach, three new hydroxylated derivatives of bisabolol oxides A and B (<b>1</b>–<b>3</b>) have been isolated from <i>M. chamomilla</i>. Plausible biogenetic pathways are presented

Skin Bleaching and Dermatologic Health of African and Afro-Caribbean Populations in the US: New Directions for Methodologically Rigorous, Multidisciplinary, and Culturally Sensitive Research

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s13555-016-0154-1">https://link.springer.com/article/10.1007/s13555-016-0154-1</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

New Triterpenoid Saponins from Ilex cornuta and Their Protective Effects against H₂O₂‑Induced Myocardial Cell Injury

Five new triterpenoid saponins, <b>1</b>–<b>5</b>, together with 10 known ones, <b>6</b>–<b>15</b> were isolated from the aerial parts of Ilex cornuta. The structures of compounds <b>1</b>–<b>5</b> were determined as 3β-<i>O</i>-α-l-arabinopyranosyl-19α,23-dihydroxy-20α-urs-12-en-28-oic acid 28-<i>O</i>-β-d-glucopyranosyl ester, <b>1</b>; 3β-<i>O</i>-β-d-glucopyranosyl-(1→2)-α-l-arabinopyranosyl-19-hydroxy-20α-urs-12-en-28-oic acid 28-<i>O</i>-β-d-glucopyranosyl ester, <b>2</b>; 19α,23-dihydroxyurs-12-en-28-oic acid 3β-<i>O</i>-β-d-glucuronopyranoside-6-<i>O</i>-methyl ester, <b>3</b>; 19α,23-dihydroxyurs-12-en-28-oic acid 3β-<i>O</i>-[β-d-glucuronopyranoside-6-<i>O</i>-methyl ester]-28-<i>O</i>-β-d-glucopyranosyl ester, <b>4</b>; and 3β-<i>O</i>-[α-l-arabinopyranosyl-(1→2)-β-d-glucuronic acid]-oleanolic acid 28-<i>O</i>-β-d-glucopyranosyl ester, <b>5</b>, on the basis of spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D and 2D NMR) and chemical reactions. Protective effects of compounds <b>1</b>–<b>15</b> were tested against H₂O₂-induced H9c2 cardiomyocyte injury, and the data showed that compounds <b>1</b>, <b>4</b>, <b>6</b>, and <b>13</b> had significant cell-protective effects. No significant DPPH radical scavenging activity was observed for compounds <b>1</b>–<b>15</b>

Quality Evaluation of Terpinen-4-ol-Type Australian Tea Tree Oils and Commercial Products: An Integrated Approach Using Conventional and Chiral GC/MS Combined with Chemometrics

GC/MS, chiral GC/MS, and chemometric techniques were used to evaluate a large set (<i>n</i> = 104) of tea tree oils (TTO) and commercial products purported to contain TTO. Twenty terpenoids were determined in each sample and compared with the standards specified by ISO-4730-2004. Several of the oil samples that were ISO compliant when distilled did not meet the ISO standards in this study primarily due to the presence of excessive <i>p</i>-cymene and/or depletion of terpinenes. Forty-nine percent of the commercial products did not meet the ISO specifications. Four terpenes, viz., α-pinene, limonene, terpinen-4-ol, and α-terpineol, present in TTOs with the (+)-isomer predominant were measured by chiral GC/MS. The results clearly indicated that 28 commercial products contained excessive (+)-isomer or contained the (+)-isomer in concentrations below the norm. Of the 28 outliers, 7 met the ISO standards. There was a substantial subset of commercial products that met ISO standards but displayed unusual enantiomeric +/– ratios. A class predictive model based on the oils that met ISO standards was constructed. The outliers identified by the class predictive model coincided with the samples that displayed an abnormal chiral ratio. Thus, chiral and chemometric analyses could be used to confirm the identification of abnormal commercial products including those that met all of the ISO standards