molecules-logo

Journal Browser

Journal Browser

Organic Chemistry in the USA

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Organic Chemistry".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 37481

Special Issue Editors


E-Mail Website
Guest Editor
Department of Chemistry, Oakland University, 146 Library Drive, Rochester, MI 48309-4479, USA
Interests: organic, organometallic, and medicinal chemistry; organic synthesis; nucleosides; heterocycles; alkynes; fluorine and fluorous; cycloisomerizations; cyclizations
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA
Interests: organic reaction mechanisms; stereoelectronic effects; organic photochemistry; DNA photocleavage; carbon-rich materials; chemistry of alkynes; radical chemistry; cyclizations; cycloaromatizations; electron upconversion; hole catalysis; high energy functional groups
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Organic chemistry has traditionally been positioned at the forefront of chemical research. It broadly encompasses the study of structure, study of properties, and chemical reactivity via the laboratory and via theoretical (in silico) methods. The study of organic reactions includes synthesis of novel molecules, natural products, drugs, polymers, etc. 

Chemists in the US has traditionally spearheaded efforts in many areas. Thus, providing a convenient avenue for the dissemination of interesting results from US laboratories is of interest for the organic chemistry community. This Special Issue aims to illustrate the most recent and pertinent developments in organic chemistry, organic synthesis, etc. The contributions will focus on a broad range of organic studies, methodologies, or reactions. 

This Special Issue of Molecules journal collects articles from the best research groups in the US, representing not only the 50 states but also unincorporated territories of the United States The readers will be able to find diverse articles on the topic of organic chemistry, including communications, full papers and reviews.

Prof. Roman Dembinski
Prof. Dr. Igor V. Alabugin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • acetals
  • acid anhydrides
  • aldehydes
  • alkanes
  • alkenes
  • alkynes
  • alcohols
  • aldehydes
  • alkyl halides
  • amides
  • amines
  • aminoacids
  • arenes
  • azo compounds
  • carboxylix acids
  • carbohydrates
  • catalysis
  • electrophiles
  • esters
  • flow
  • fluorine
  • fluorous
  • heterocycles
  • hydrogenation
  • isocyanates
  • ketones
  • methatesis
  • nitriles
  • nucleophiles
  • nucleosides
  • nucleotides
  • organic synthesis
  • photochemistry
  • radical reactions
  • rearrangements
  • stereoselective synthesis
  • stereospecific synthesis
  • total synthesis

Published Papers (11 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

11 pages, 1791 KiB  
Communication
The Synthesis and Initial Evaluation of MerTK Targeted PET Agents
by Li Wang, Yubai Zhou, Xuedan Wu, Xinrui Ma, Bing Li, Ransheng Ding, Michael A. Stashko, Zhanhong Wu, Xiaodong Wang and Zibo Li
Molecules 2022, 27(5), 1460; https://doi.org/10.3390/molecules27051460 - 22 Feb 2022
Viewed by 2044
Abstract
MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to [...] Read more.
MerTK (Mer tyrosine kinase), a receptor tyrosine kinase, is ectopically or aberrantly expressed in numerous human hematologic and solid malignancies. Although a variety of MerTK targeting therapies are being developed to enhance outcomes for patients with various cancers, the sensitivity of tumors to MerTK suppression may not be uniform due to the heterogeneity of solid tumors and different tumor stages. In this report, we develop a series of radiolabeled agents as potential MerTK PET (positron emission tomography) agents. In our initial in vivo evaluation, [18F]-MerTK-6 showed prominent uptake rate (4.79 ± 0.24%ID/g) in B16F10 tumor-bearing mice. The tumor to muscle ratio reached 1.86 and 3.09 at 0.5 and 2 h post-injection, respectively. In summary, [18F]-MerTK-6 is a promising PET agent for MerTK imaging and is worth further evaluation in future studies. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Figure 1

12 pages, 3053 KiB  
Article
Preparation of Deuterium Labeled Compounds by Pd/C-Al-D2O Facilitated Selective H-D Exchange Reactions
by Anne Kokel, Dora Kadish and Béla Török
Molecules 2022, 27(3), 614; https://doi.org/10.3390/molecules27030614 - 18 Jan 2022
Cited by 4 | Viewed by 2773
Abstract
The chemo/regioselective H-D exchange of amino acids and synthetic building blocks by an environmentally benign Pd/C-Al-D2O catalytic system is described. Due to the importance of isotope labeled compounds in medicinal chemistry and structural biology, notably their use as improved drug candidates [...] Read more.
The chemo/regioselective H-D exchange of amino acids and synthetic building blocks by an environmentally benign Pd/C-Al-D2O catalytic system is described. Due to the importance of isotope labeled compounds in medicinal chemistry and structural biology, notably their use as improved drug candidates and biological probes, the efficient and selective deuteration methods are of great interest. The approach is based on selective H-D exchange reactions where the deuterium source is simple D2O. D2 gas is generated in situ from the reaction of aluminum and D2O, while the commercially available palladium catalyst assists the H-D exchange reaction. The high selectivity and efficiency, as well as the simplicity and safe nature of the procedure make this method an environmentally benign alternative to current alternatives. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Figure 1

10 pages, 990 KiB  
Article
Precursor-Directed Biosynthesis of Aminofulvenes: New Chalanilines from Endophytic Fungus Chalara sp.
by Mahsa Khoshbakht, Jason Srey, Donovon A. Adpressa, Annika Jagels and Sandra Loesgen
Molecules 2021, 26(15), 4418; https://doi.org/10.3390/molecules26154418 - 22 Jul 2021
Cited by 2 | Viewed by 2469
Abstract
The plant endophyte Chalara sp. is able to biotransform the epigenetic modifier vorinostat to form unique, aniline-containing polyketides named chalanilines. Here, we sought to expand the chemical diversity of chalaniline A-type molecules by changing the aniline moiety in the precursor vorinostat. In total, [...] Read more.
The plant endophyte Chalara sp. is able to biotransform the epigenetic modifier vorinostat to form unique, aniline-containing polyketides named chalanilines. Here, we sought to expand the chemical diversity of chalaniline A-type molecules by changing the aniline moiety in the precursor vorinostat. In total, twenty-three different vorinostat analogs were prepared via two-step synthesis, and nineteen were incorporated by the fungus into polyketides. The highest yielding substrates were selected for large-scale precursor-directed biosynthesis and five novel compounds, including two fluorinated chalanilines, were isolated, purified, and structurally characterized. Structure elucidation relied on 1D and 2D NMR techniques and was supported by low- and high-resolution mass spectrometry. All compounds were tested for their bioactivity but were not active in antimicrobial or cell viability assays. Aminofulvene-containing natural products are rare, and this high-yielding, precursor-directed process allows for the diversification of this class of compounds. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Graphical abstract

11 pages, 4336 KiB  
Article
A Formal Rearrangement of Allylic Silanols
by Ranjeet A. Dhokale, Frederick J. Seidl and Shyam Sathyamoorthi
Molecules 2021, 26(13), 3829; https://doi.org/10.3390/molecules26133829 - 23 Jun 2021
Cited by 10 | Viewed by 3006
Abstract
We show that 1M aqueous HCl/THF or NaBH4/DMF allows for demercurative ring-opening of cyclic organomercurial synthons into secondary silanol products bearing terminal alkenes. We had previously demonstrated that primary allylic silanols are readily transformed into cyclic organomercurials using Hg(OTf)2/NaHCO [...] Read more.
We show that 1M aqueous HCl/THF or NaBH4/DMF allows for demercurative ring-opening of cyclic organomercurial synthons into secondary silanol products bearing terminal alkenes. We had previously demonstrated that primary allylic silanols are readily transformed into cyclic organomercurials using Hg(OTf)2/NaHCO3 in THF. Overall, this amounts to a facile two-step protocol for the rearrangement of primary allylic silanol substrates. Computational investigations suggest that this rearrangement is under thermodynamic control and that the di-tert-butylsilanol protecting group is essential for product selectivity. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Graphical abstract

26 pages, 3823 KiB  
Article
Synthesis of Carbohydrate Based Macrolactones and Their Applications as Receptors for Ion Recognition and Catalysis
by Surya B. Adhikari, Anji Chen and Guijun Wang
Molecules 2021, 26(11), 3394; https://doi.org/10.3390/molecules26113394 - 3 Jun 2021
Cited by 5 | Viewed by 2794
Abstract
Glycomacrolactones exhibit many interesting biological properties, and they are also important in molecular recognitions and for supramolecular chemistry. Therefore, it is important to be able to access glycomacrocycles with different sizes and functionality. A new series of carbohydrate-based macrocycles containing triazole and lactone [...] Read more.
Glycomacrolactones exhibit many interesting biological properties, and they are also important in molecular recognitions and for supramolecular chemistry. Therefore, it is important to be able to access glycomacrocycles with different sizes and functionality. A new series of carbohydrate-based macrocycles containing triazole and lactone moieties have been designed and synthesized. The synthesis features an intramolecular nucleophilic substitution reaction for the macrocyclization step. In this article, the effect of some common sulfonate leaving groups is evaluated for macrolactonization. Using tosylate gave good selectivity for monolactonization products with good yields. Fourteen different macrocycles have been synthesized and characterized, of which eleven macrocycles are from cyclization of the C1 to C6 positions of N-acetyl D-glucosamine derivatives and three others from C2 to C6 cyclization of functionalized D-glucosamine derivatives. These novel macrolactones have unique structures and demonstrate interesting anion binding properties, especially for chloride. The macrocycles containing two triazoles form complexes with copper sulfate, and they are effective ligands for copper sulfate mediated azide-alkyne cycloaddition reactions (CuAAC). In addition, several macrocycles show some selectivity for different alkynes. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Figure 1

10 pages, 2960 KiB  
Article
Sweet-Tasting Ionic Conjugates of Local Anesthetics and Vasoconstrictors
by John K. Neubert, Alexander A. Oliferenko, Polina V. Oliferenko, Sergey V. Emets, David A. Ostrov, Gary I. Altschuler, Joe Calkins, Jay Wickersham, Robert Hromas and Iryna O. Lebedyeva
Molecules 2021, 26(4), 983; https://doi.org/10.3390/molecules26040983 - 12 Feb 2021
Viewed by 2631
Abstract
Local anesthetics are widely utilized in dentistry, cosmetology, and medicine. Local anesthesia is essential to providing a pain-free experience during dental and local surgeries as well as cosmetic procedures. However, the injection itself may produce discomfort and be a source of aversion. A [...] Read more.
Local anesthetics are widely utilized in dentistry, cosmetology, and medicine. Local anesthesia is essential to providing a pain-free experience during dental and local surgeries as well as cosmetic procedures. However, the injection itself may produce discomfort and be a source of aversion. A novel approach toward the taste modulation of local anesthetics is proposed, in which the anesthetics of the “-caine” family serve as cations and are coupled with anionic sweeteners such as saccharinate and acesulfamate. Ionic conjugates of vasoconstrictor epinephrine such as epinephrine saccharinate and epinephrine acesulfamate have also been synthesized. Novel ionic conjugates were developed using anion exchange techniques. Reported compounds are sweet-tasting and are safe to use both topically and as injections. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Graphical abstract

14 pages, 2313 KiB  
Article
Development of Second Generation Activity-Based Chemical Probes for Sirtuins
by Alyson M. Curry, Elizabeth Barton, Wenjia Kang, Daniel V. Mongeluzi and Yana Cen
Molecules 2021, 26(1), 11; https://doi.org/10.3390/molecules26010011 - 22 Dec 2020
Cited by 5 | Viewed by 2722
Abstract
NAD+ (nicotinamide adenine dinucleotide)-dependent protein deacylases, namely, the sirtuins, are important cell adaptor proteins that alter cell physiology in response to low calorie conditions. They are thought to mediate the beneficial effects of calorie restriction to extend longevity and improve health profiles. [...] Read more.
NAD+ (nicotinamide adenine dinucleotide)-dependent protein deacylases, namely, the sirtuins, are important cell adaptor proteins that alter cell physiology in response to low calorie conditions. They are thought to mediate the beneficial effects of calorie restriction to extend longevity and improve health profiles. Novel chemical probes are highly desired for a better understanding of sirtuin’s roles in various biological processes. We developed a group of remarkably simple activity-based chemical probes for the investigation of active sirtuin content in complex native proteomes. These probes harbor a thioacyllysine warhead, a diazirine photoaffinity tag, as well as a terminal alkyne bioorthogonal functional group. Compared to their benzophenone-containing counterparts, these new probes demonstrated improved labeling efficiency and sensitivity, shortened irradiation time, and reduced background signal. They were applied to the labeling of individual recombinant proteins, protein mixtures, and whole cell lysate. These cell permeable small molecule probes also enabled the cellular imaging of sirtuin activity change. Taken together, our study provides new chemical biology tools and future drug discovery strategies for perturbing the activity of different sirtuin isoforms. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Figure 1

16 pages, 1295 KiB  
Article
Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone
by Tania J. Bellinger, Teavian Harvin, Ti’Bran Pickens-Flynn, Nataleigh Austin, Samuel H. Whitaker, Mai Ling C. Tang Yuk Tutein, Dabria T. Hukins, Nichele Deese and Fenghai Guo
Molecules 2020, 25(9), 2128; https://doi.org/10.3390/molecules25092128 - 1 May 2020
Cited by 4 | Viewed by 4234
Abstract
Grignard reagents undergo conjugate addition to thiochromones catalyzed by copper salts to afford 2-substituted-thiochroman-4-ones, both 2-alkylthiochroman-4-ones and thioflavanones (2-arylthiochroman-4-ones), in good yields with trimethylsilyl chloride (TMSCl) as an additive. The best yields of 1,4-adducts can be attained with CuCN∙2LiCl as the copper source. [...] Read more.
Grignard reagents undergo conjugate addition to thiochromones catalyzed by copper salts to afford 2-substituted-thiochroman-4-ones, both 2-alkylthiochroman-4-ones and thioflavanones (2-arylthiochroman-4-ones), in good yields with trimethylsilyl chloride (TMSCl) as an additive. The best yields of 1,4-adducts can be attained with CuCN∙2LiCl as the copper source. Excellent yields of 2-alkyl-substituted thiochroman-4-ones and thioflavanones (2-aryl substituted) are attained with a broad range of Grignard reagents. This approach works well with both alkyl and aromatic Grignard reagents, thus providing a unified synthetic approach to privileged 2-substituted thiochroman-4-ones and a potential valuable precursor for further synthetic applications towards many pharmaceutically active molecules. The use of commercially available and/or readily prepared Grignard reagents will expedite the synthesis of a large library of both 2-alkyl substituted thiochroman-4-ones and thioflavanones for additional synthetic applications. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Graphical abstract

7 pages, 1510 KiB  
Communication
Synthesis of the C3 and C1 Constitutional Isomers of Trifluorosubphthalocyanine and Their Fluorescence within MDA-MB-231 Breast Tumor Cells
by Rosemarie L. Calandrino, Katherine J. McAuliffe, Lauren E. Dolmage and Evan R. Trivedi
Molecules 2019, 24(21), 3832; https://doi.org/10.3390/molecules24213832 - 24 Oct 2019
Cited by 3 | Viewed by 2816
Abstract
Metal tetrapyrrole macrocycles such as porphyrins and chlorins are ubiquitous in nature. Synthetic analogs, including phthalocyanines, have found applications in medicine, particularly as photosensitizers for photodynamic therapy and as fluorescent imaging probes. Tripyrrolic macrocycles, called subphthalocyanines (SPcs) with a smaller boron atom at [...] Read more.
Metal tetrapyrrole macrocycles such as porphyrins and chlorins are ubiquitous in nature. Synthetic analogs, including phthalocyanines, have found applications in medicine, particularly as photosensitizers for photodynamic therapy and as fluorescent imaging probes. Tripyrrolic macrocycles, called subphthalocyanines (SPcs) with a smaller boron atom at their core, have similar potential as optical agents. We have recently reported a series of mixed fluorinated SPcs with varying aromaticity, showing that electronic absorption and emission are synthetically tunable across the far visible region, and that the inclusion of 4–12 peripheral fluorine atoms results in strong fluorescence within MDA-MB-231 breast tumor cells. Further probing this system, we report herein the synthesis and characterization of boron trifluorosubphthalocyanine chloride (F3SPc). The constitutional isomers F3SPc(C3) and F3SPc(C1) are readily separable by chromatography, and their identity and purity have been confirmed by 1H NMR, 19F NMR, HR APCI-MS, and HPLC. Unsurprisingly, these structurally similar F3SPcs have identical electronic absorption (λmax = 557 nm; tetrahydrofuran (THF)) and emission (λem = 574 nm; Φf = 0.27–0.28; THF). Strong fluorescence from MDA-MB-231 breast tumor cells was observed following treatment with F3SPc(C3) and F3SPc(C1) (50 µM F3SPc, 15 min), further highlighting the importance of even a limited number of peripheral fluorine atoms for this type of application. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Figure 1

Review

Jump to: Research

44 pages, 20643 KiB  
Review
Recent Advances in Macrocyclic Drugs and Microwave-Assisted and/or Solid-Supported Synthesis of Macrocycles
by Dianqing Sun
Molecules 2022, 27(3), 1012; https://doi.org/10.3390/molecules27031012 - 2 Feb 2022
Cited by 11 | Viewed by 4387
Abstract
Macrocycles represent attractive candidates in organic synthesis and drug discovery. Since 2014, nineteen macrocyclic drugs, including three radiopharmaceuticals, have been approved by FDA for the treatment of bacterial and viral infections, cancer, obesity, immunosuppression, etc. As such, new synthetic methodologies and high throughput [...] Read more.
Macrocycles represent attractive candidates in organic synthesis and drug discovery. Since 2014, nineteen macrocyclic drugs, including three radiopharmaceuticals, have been approved by FDA for the treatment of bacterial and viral infections, cancer, obesity, immunosuppression, etc. As such, new synthetic methodologies and high throughput chemistry (e.g., microwave-assisted and/or solid-phase synthesis) to access various macrocycle entities have attracted great interest in this chemical space. This article serves as an update on our previous review related to macrocyclic drugs and new synthetic strategies toward macrocycles (Molecules, 2013, 18, 6230). In this work, I first reviewed recent FDA-approved macrocyclic drugs since 2014, followed by new advances in macrocycle synthesis using high throughput chemistry, including microwave-assisted and/or solid-supported macrocyclization strategies. Examples and highlights of macrocyclization include macrolactonization and macrolactamization, transition-metal catalyzed olefin ring-closure metathesis, intramolecular C–C and C–heteroatom cross-coupling, copper- or ruthenium-catalyzed azide–alkyne cycloaddition, intramolecular SNAr or SN2 nucleophilic substitution, condensation reaction, and multi-component reaction-mediated macrocyclization, and covering the literature since 2010. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Figure 1

37 pages, 15150 KiB  
Review
Synthesis of Naphthoquinone Derivatives: Menaquinones, Lipoquinones and Other Vitamin K Derivatives
by Margaret Braasch-Turi and Debbie C. Crans
Molecules 2020, 25(19), 4477; https://doi.org/10.3390/molecules25194477 - 29 Sep 2020
Cited by 15 | Viewed by 6184
Abstract
Menaquinones are a class of isoprenoid molecules that have important roles in human biology and bacterial electron transport, and multiple methods have been developed for their synthesis. These compounds consist of a methylnaphthoquinone (MK) unit and an isoprene side chain, such as found [...] Read more.
Menaquinones are a class of isoprenoid molecules that have important roles in human biology and bacterial electron transport, and multiple methods have been developed for their synthesis. These compounds consist of a methylnaphthoquinone (MK) unit and an isoprene side chain, such as found in vitamin K1 (phylloquinone), K2, and other lipoquinones. The most common naturally occurring menaquinones contain multiple isoprene units and are very hydrophobic, rendering it difficult to evaluate the biological activity of these compounds in aqueous assays. One way to overcome this challenge has been the application of truncated MK-derivatives for their moderate solubility in water. The synthesis of such derivatives has been dominated by Friedel-Crafts alkylation with BF3∙OEt2. This attractive method occurs over two steps from commercially available starting materials, but it generally produces low yields and a mixture of isomers. In this review, we summarize reported syntheses of both truncated and naturally occurring MK-derivatives that encompass five different synthetic strategies: Nucleophilic ring methods, metal-mediated reactions, electrophilic ring methods, pericyclic reactions, and homologation and side chain extensions. The advantages and disadvantages of each method are discussed, identifying methods with a focus on high yields, regioselectivity, and stereochemistry leading to a detailed overview of the reported chemistry available for preparation of these compounds. Full article
(This article belongs to the Special Issue Organic Chemistry in the USA)
Show Figures

Figure 1

Back to TopTop