DOCSLIB.ORG

Last Decade of Unconventional Methodologies for the Synthesis Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Last Decade of Unconventional Methodologies for the Synthesis Of Review molecules Last Decade of Unconventional Methodologies for theReview Synthesis of Substituted Benzofurans Last Decade of Unconventional Methodologies for the Lucia Chiummiento *, Rosarita D’Orsi, Maria Funicello and Paolo Lupattelli Synthesis of Substituted Benzofurans Department of Science, Via dell’Ateneo Lucano, 10, 85100 Potenza, Italy; [email protected] (R.D.); [email protected] (M.F.); [email protected] (P.L.) Lucia Chiummiento * , Rosarita D’Orsi, Maria Funicello and Paolo Lupattelli * Correspondence: [email protected] Department of Science, Via dell’Ateneo Lucano, 10, 85100 Potenza, Italy; [email protected] (R.D.); Academic Editor: Gianfranco Favi [email protected] (M.F.); [email protected] (P.L.) Received:* Correspondence: 22 April 2020; [email protected] Accepted: 13 May 2020; Published: 16 May 2020 Abstract:Academic This Editor: review Gianfranco describes Favi the progress of the last decade on the synthesis of substituted Received: 22 April 2020; Accepted: 13 May 2020; Published: 16 May 2020 benzofurans, which are useful scaffolds for the synthesis of numerous natural products and pharmaceuticals.Abstract: This In review particular, describes new the intramolecular progress of the and last decadeintermolecular on the synthesis C–C and/or of substituted C–O bond- formingbenzofurans, processes, which with aretransition-metal useful scaffolds catalysi for thes or synthesis metal-free of numerous are summarized. natural products(1) Introduction. and (2) Ringpharmaceuticals. generation via In particular, intramolecular new intramolecular cyclization. and (2.1) intermolecular C7a–O bond C–C formation: and/or C–O (route bond-forming a). (2.2) O– C2 bondprocesses, formation: with transition-metal (route b). (2.3) catalysis C2–C3 bond or metal-free formation: are summarized. (route c). (2.4) (1) Introduction.C3–C3a bond (2) formation: Ring generation via intramolecular cyclization. (2.1) C7a–O bond formation: (route a). (2.2) O–C2 (route d). (3) Ring generation via intermolecular cyclization. (3.1) C7a-O and C3–C3a bond bond formation: (route b). (2.3) C2–C3 bond formation: (route c). (2.4) C3–C3a bond formation: formation (route a + d). (3.2) O–C2 and C2–C3 bond formation: (route b + c). (3.3) O–C2 and C3–C3a (route d). (3) Ring generation via intermolecular cyclization. (3.1) C7a-O and C3–C3a bond formation bond(route formation: a + d). (route (3.2) O–C2 b + d). and (4) C2–C3 Benzannulation. bond formation: (5) Conclusion. (route b + c). (3.3) O–C2 and C3–C3a bond formation: (route b + d). (4) Benzannulation. (5) Conclusion. Keywords: synthesis of benzofurans; intra-molecular approach; inter-molecular approach Keywords: synthesis of benzofurans; intra-molecular approach; inter-molecular approach 1. Introduction 1. Introduction Benzofuran (BF) and 2,3-dihydrobenzofuran (2,3-DBF) are key structural units in a variety of Benzofuran (BF) and 2,3-dihydrobenzofuran (2,3-DBF) are key structural units in a variety of biologically active natural products (Figure 1) and represent the core structures of many approved biologically active natural products (Figure1) and represent the core structures of many approved drugs,drugs, as well as well as lead-design as lead-design developments developments from from naturalnatural products products [1 –[1–4].4]. 3 3 2 2 O O BF 2,3-DBF Figure 1. Structures of benzofuran (BF) and 2,3-dihydrobenzofuran (2,3-DBF). Figure 1. Structures of benzofuran (BF) and 2,3-dihydrobenzofuran (2,3-DBF). BF is a completely aromatic flat structure, while 2,3-DBF bears two prochiral sp3 carbons on the heterocycle,BF is a completely placing thearomatic substituents flat structure, out of the while benzofuryl 2,3-DBF plane. bears Naturally two prochiral occurring sp3 compounds carbons on the heterocycle,bearing BFplacing and their the derivativessubstituents show out aof broad the benzofuryl range of pharmacological plane. Naturally activities. occurring Among compounds them, bearingamurensin BF and H their (or viniferifuran) derivatives show1 (Figure a broad2) displayed range anti-inflammatoryof pharmacological e ff ectactivities. on an asthma-like Among them, amurensinreaction H induced (or viniferifuran) in mice [5], while1 (Figure Anigopreissin 2) displayed A 2 showedanti-inflammatory low antimicrobial effect activityon an asthma-like against reactionStaphylococcus. induced in aureus miceand [5],S. while pyogene Anigopreissin[6] and was also A 2 discovered showed low as an antimicrobial inhibitor of HIV-1 activity reverse against Staphylococcus.transcriptase aureus (IC50 =and8 mM), S. pyogene including [6] two and mutant was enzymesalso discovered resistant to as the an clinical inhibitor drug of nevirapine HIV-1 reverse [7]. transcriptase (IC50 = 8 mM), including two mutant enzymes resistant to the clinical drug nevirapine [7]. Molecules 2020, 25, 2327; doi:10.3390/molecules25102327 www.mdpi.com/journal/molecules Molecules 2020, 24, x; doi: www.mdpi.com/journal/molecules Molecules 2020, 25, 2327 2 of 52 Molecules 2020, 24, x 2 of 54 Figure 2. RepresentativeRepresentative pharmacologica pharmacologicallylly active BF derivatives. Permethylated anigopreissin anigopreissin A A (PAA) (PAA) 3 showed inhibitory activity for human hepatoma cell proliferation [[8,9],8,9], whilewhile di differentfferent benzofuran benzofuran derivatives derivatives have have shown shown pharmacological pharmacological properties properties such suchas anticancer as anticancer [10,11], antiviral[10,11], [12an,tiviral13], anti-Alzheimer [12,13], anti-Alzheimer0s disease [14′,s15 disease], together [14,15], with antiparasitic together with [16], antiparasiticantitubercular [16], [17 antitubercular], and antibacterial [17], and [18, 19antibacter] activities.ial [18,19] Prescribed activities. agents Prescribed featuring agents the benzofuran featuring scaffold include the antidepressant ( )-BPAP 4, the antiarrythmic amiodarone 5 [20], the clinical the benzofuran scaffold include the antidepressant− (−)-BPAP 4, the antiarrythmic amiodarone 5 [20], β thecandidate clinical drug candidate for renal drug and for ovarian renal and cancers ovarian BNC105 cancers6 [BNC10521], and 6 the [21], inhibitor and the of inhibitor A fibril of formation Aβ fibril formation7 [2]. Such 7 a variety[2]. Such of a biological variety of and biological pharmacological and pharmacological activities make activities BF an important make BF pharmacophore an important pharmacophorefor the development for the of newdevelopment drugs. of new drugs. Thus, synthetic accessaccess toto benzofurans benzofurans is is of of considerable considerable interest, interest, and and numerous numerous approaches approaches to this to thisscaff scaffoldold have have been been disclosed disclosed in the in literature. the literature. Herein, Herein, we deal we with deal the with most the recent most literature, recent literature, which is whichnot included is not included in the appeared in the appeared reviews ofreviews the last of decade the last (2009–2020) decade (2009–2020) [22]. [22]. The review ofof DeDe Luca Luca et et al. al. [23 [23]] dealt dealt with with the the synthesis synthesis of 2-substituted-benzofurans of 2-substituted-benzofurans up to up 2009, to 2009,while while the one the of Abu-Hashemone of Abu-Hashem et al. [24 ]et was al. an[24] overview was an aboutoverview the diaboutfferent the approaches different toapproaches benzofurans. to benzofurans.Very recently, Very from recently, the same from authors, the same a chapter authors, in Advances a chapter in in Heterocyclic Advances in Chemistry Heterocyclic [25 ]Chemistry and three [25]reviews and havethree beenreviews published have been in which published the full in which perspective the full of perspective reactivity of of benzofurans reactivity of [26 benzofurans], advances [26],in the advances synthesis in of the biologically synthesis potentof biologically compounds potent bearing compounds at least bearing one benzofuran at least one moiety benzofuran in their moietystructures in [their27] and structures the recent [27] reports and onthe therecent total re synthesisports on of the natural total productssynthesis containing of natural at products least one containingbenzofuran at moiety least one in their benzofuran complex moiety structures in [their28] have complex been structures discussed. [28] A review have onbeen synthetic discussed. routes A reviewfor synthesis on synthetic of benzofuran-based routes for synthesis compounds of benzof appeareduran-based in 2017 compounds [29] and at appeared the least onein 2017 summarizes [29] and atthe the recent least studies one summarizes on the various the aspectsrecent studies of benzofurans on the various derivatives, aspects including of benzofurans their natural derivatives, sources, includingbiological their activities natural and sources, drug prospects, biological and activities chemical and synthesis, drug prospects, as well asand the chemical relationship synthesis, between as wellthe bioactivities as the relationship and structures between [30 the]. bioactivities and structures [30]. In this this plethora plethora of methodologies, of methodologies, different different classifications classifications were used, were subdividing used, subdividing the data into the synthesisdata into of synthesis 2- or 3-substituted of 2- or 3-substitutedor 2,3-disubstituted or 2,3-disubstituted benzofurans [31,32], benzofurans or into transition-metal- [31,32], or into catalyzedtransition-metal-catalyzed
Load more

Recommended publications
  • Retention Indices for Frequently Reported Compounds of Plant Essential Oils
    Retention Indices for Frequently Reported Compounds of Plant Essential Oils V. I. Babushok,a) P. J. Linstrom, and I. G. Zenkevichb) National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA (Received 1 August 2011; accepted 27 September 2011; published online 29 November 2011) Gas chromatographic retention indices were evaluated for 505 frequently reported plant essential oil components using a large retention index database. Retention data are presented for three types of commonly used stationary phases: dimethyl silicone (nonpolar), dimethyl sili- cone with 5% phenyl groups (slightly polar), and polyethylene glycol (polar) stationary phases. The evaluations are based on the treatment of multiple measurements with the number of data records ranging from about 5 to 800 per compound. Data analysis was limited to temperature programmed conditions. The data reported include the average and median values of retention index with standard deviations and confidence intervals. VC 2011 by the U.S. Secretary of Commerce on behalf of the United States. All rights reserved. [doi:10.1063/1.3653552] Key words: essential oils; gas chromatography; Kova´ts indices; linear indices; retention indices; identification; flavor; olfaction. CONTENTS 1. Introduction The practical applications of plant essential oils are very 1. Introduction................................ 1 diverse. They are used for the production of food, drugs, per- fumes, aromatherapy, and many other applications.1–4 The 2. Retention Indices ........................... 2 need for identification of essential oil components ranges 3. Retention Data Presentation and Discussion . 2 from product quality control to basic research. The identifi- 4. Summary.................................. 45 cation of unknown compounds remains a complex problem, in spite of great progress made in analytical techniques over 5.
    [Show full text]
  • Molecular Signatures of G-Protein-Coupled Receptors A
    REVIEW doi:10.1038/nature11896 Molecular signatures of G-protein-coupled receptors A. J. Venkatakrishnan1, Xavier Deupi2, Guillaume Lebon1,3,4,5, Christopher G. Tate1, Gebhard F. Schertler2,6 & M. Madan Babu1 G-protein-coupled receptors (GPCRs) are physiologically important membrane proteins that sense signalling molecules such as hormones and neurotransmitters, and are the targets of several prescribed drugs. Recent exciting developments are providing unprecedented insights into the structure and function of several medically important GPCRs. Here, through a systematic analysis of high-resolution GPCR structures, we uncover a conserved network of non-covalent contacts that defines the GPCR fold. Furthermore, our comparative analysis reveals characteristic features of ligand binding and conformational changes during receptor activation. A holistic understanding that integrates molecular and systems biology of GPCRs holds promise for new therapeutics and personalized medicine. ignal transduction is a fundamental biological process that is comprehensively, and in the process expand the current frontiers of required to maintain cellular homeostasis and to ensure coordi- GPCR biology. S nated cellular activity in all organisms. Membrane proteins at the In this analysis, we objectively compare known structures and reveal cell surface serve as the communication interface between the cell’s key similarities and differences among diverse GPCRs. We identify a external and internal environments. One of the largest and most diverse consensus structural scaffold of GPCRs that is constituted by a network membrane protein families is the GPCRs, which are encoded by more of non-covalent contacts between residues on the transmembrane (TM) than 800 genes in the human genome1. GPCRs function by detecting a helices.
    [Show full text]
  • Synthesis of Indole and Oxindole Derivatives Incorporating Pyrrolidino, Pyrrolo Or Imidazolo Moieties
    From DEPARTMENT OF BIOSCIENCES AT NOVUM Karolinska Institutet, Stockholm, Sweden SYNTHESIS OF INDOLE AND OXINDOLE DERIVATIVES INCORPORATING PYRROLIDINO, PYRROLO OR IMIDAZOLO MOIETIES Stanley Rehn Stockholm 2004 All previously published papers have been reproduced with permission from the publishers. Published and printed by Karolinska University Press Box 200, SE-171 77 Stockholm, Sweden © Stanley Rehn, 2004 ISBN 91-7140-169-5 Till Amanda Abstract The focus of this thesis is on the synthesis of oxindole- and indole-derivatives incorporating pyrrolidins, pyrroles or imidazoles moieties. Pyrrolidino-2-spiro-3’-oxindole derivatives have been prepared in high yielding three-component reactions between isatin, α-amino acid derivatives, and suitable dipolarophiles. Condensation between isatin and an α-amino acid yielded a cyclic intermediate, an oxazolidinone, which decarboxylate to give a 1,3-dipolar species, an azomethine ylide, which have been reacted with several dipolarophiles such as N- benzylmaleimide and methyl acrylate. Both N-substituted and N-unsubstituted α- amino acids have been used as the amine component. 3-Methyleneoxindole acetic acid ethyl ester was reacted with p- toluenesulfonylmethyl isocyanide (TosMIC) under basic conditions which gave (in a high yield) a colourless product. Two possible structures could be deduced from the analytical data, a pyrroloquinolone and an isomeric ß-carboline. To clarify which one of the alternatives that was actually formed from the TosMIC reaction both the ß- carboline and the pyrroloquinolone were synthesised. The ß-carboline was obtained when 3-ethoxycarbonylmethyl-1H-indole-2-carboxylic acid ethyl ester was treated with a tosylimine. An alternative synthesis of the pyrroloquinolone was performed via a reduction of a 2,3,4-trisubstituted pyrrole obtained in turn by treatment of a vinyl sulfone with ethyl isocyanoacetate under basic conditions.
    [Show full text]
  • Phosphodiesterase Isoforms and Camp Compartments in The
    University of Groningen Phosphodiesterase isoforms and cAMP compartments in the development of new therapies for obstructive pulmonary diseases Schmidt, Martina; Cattani-Cavalieri, Isabella; Nuñez, Francisco J; Ostrom, Rennolds S Published in: Current Opinion in Pharmacology DOI: 10.1016/j.coph.2020.05.002 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2020 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Schmidt, M., Cattani-Cavalieri, I., Nuñez, F. J., & Ostrom, R. S. (2020). Phosphodiesterase isoforms and cAMP compartments in the development of new therapies for obstructive pulmonary diseases. Current Opinion in Pharmacology, 51, 34-42. https://doi.org/10.1016/j.coph.2020.05.002 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • Electrooxidation Enables Highly Regioselective Dearomative Annulation of Indole and Benzofuran Derivatives
    ARTICLE https://doi.org/10.1038/s41467-019-13829-4 OPEN Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives Kun Liu1, Wenxu Song1, Yuqi Deng1, Huiyue Yang1, Chunlan Song1, Takfaoui Abdelilah1, Shengchun Wang 1, Hengjiang Cong 1, Shan Tang1 & Aiwen Lei1* 1234567890():,; The dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functio- nalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate- determining step. 1 College of Chemistry and Molecular Sciences, Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, P. R. China. *email: aiwenlei@whu. edu.cn NATURE COMMUNICATIONS | (2020) 11:3 | https://doi.org/10.1038/s41467-019-13829-4 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-13829-4 reaking the aromatic systems of electron-rich arenes or fused indolines (Fig. 1a)39–44. Therefore, it is highly appealing to heteroarenes provides three-dimensional chemicals of high develop efficient approaches to allow for their preparation.
    [Show full text]
  • Benzofuran Synthesis Through Iodocyclization Reactions: Recent Advances
    MOJ Bioorganic & Organic Chemistry Mini Review Open Access Benzofuran synthesis through iodocyclization reactions: recent advances Abstract Volume 1 Issue 7 - 2017 Recent advancements (2014-17) in the benzofuran synthesis through iodocyclization Saurabh Mehta have been summarized. The successful use of various iodinating agents, bases, additives Department of Applied Chemistry, Delhi Technological etc. make iodocyclization a versatile and efficient methodology. The methodology has University, India been applied for the synthesis of more complex benzofuran derivatives, and may open interesting avenues in the area of heterocyclic chemistry (Figure 1). Correspondence: Saurabh Mehta, Department of Applied O-LG Chemistry, Delhi Technological University, Bawana Road, Delhi, + O R1 I 1 2 110042 India, Tel +9188 0066 5868, R R Email [email protected], [email protected] R2 I Received: December 17, 2017 | Published: December 29, 2017 LG = H, Me or other Protecting group 1 R = H, Me, OMe, I, CO2Me, etc. R2 = H, aryl, alkyl, alkenyl, etc. Figure 1 Keywords: annulations, alkyne, benzofuran, iodocyclization, heterocycle Introduction derivatives were obtained in high yields (84%−100%) under mild conditions. The authors demonstrated that the choice of bis(2,4,6- Benzo[b]furan is a privileged heterocyclic scaffold. Several collidine)iodonium hexafluorophosphate [I(coll)2PF6] as the compounds containing this scaffold have interesting biological iodinating agent was necessary for the success of the reaction. Also, 1 activities, such as anti-cancer, anti-viral, anti-inflammatory, etc. Few the ethoxyethyl ether group acted as a protecting group as well as a 2 derivatives are even used as commercial drugs, such as Amiodarone, good leaving group.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness Et Al
    USOO6264,917B1 (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness et al. (45) Date of Patent: Jul. 24, 2001 (54) TARGETED ULTRASOUND CONTRAST 5,733,572 3/1998 Unger et al.. AGENTS 5,780,010 7/1998 Lanza et al. 5,846,517 12/1998 Unger .................................. 424/9.52 (75) Inventors: Jo Klaveness; Pál Rongved; Dagfinn 5,849,727 12/1998 Porter et al. ......................... 514/156 Lovhaug, all of Oslo (NO) 5,910,300 6/1999 Tournier et al. .................... 424/9.34 FOREIGN PATENT DOCUMENTS (73) Assignee: Nycomed Imaging AS, Oslo (NO) 2 145 SOS 4/1994 (CA). (*) Notice: Subject to any disclaimer, the term of this 19 626 530 1/1998 (DE). patent is extended or adjusted under 35 O 727 225 8/1996 (EP). U.S.C. 154(b) by 0 days. WO91/15244 10/1991 (WO). WO 93/20802 10/1993 (WO). WO 94/07539 4/1994 (WO). (21) Appl. No.: 08/958,993 WO 94/28873 12/1994 (WO). WO 94/28874 12/1994 (WO). (22) Filed: Oct. 28, 1997 WO95/03356 2/1995 (WO). WO95/03357 2/1995 (WO). Related U.S. Application Data WO95/07072 3/1995 (WO). (60) Provisional application No. 60/049.264, filed on Jun. 7, WO95/15118 6/1995 (WO). 1997, provisional application No. 60/049,265, filed on Jun. WO 96/39149 12/1996 (WO). 7, 1997, and provisional application No. 60/049.268, filed WO 96/40277 12/1996 (WO). on Jun. 7, 1997. WO 96/40285 12/1996 (WO). (30) Foreign Application Priority Data WO 96/41647 12/1996 (WO).
    [Show full text]
  • An Update on Natural Occurrence and Biological Activity of Benzofurans
    Acta Scientific MEDICAL SCIENCES (ISSN: 2582-0931) Volume 4 Issue 10 October 2020 Review Article An Update on Natural Occurrence and Biological Activity of Benzofurans Kavita Khatana* and Anjali Gupta Received: June 28, 2020 Department of Chemistry, School of Basic and Applied Sciences, Galgotias Published: September 21, 2020 University, Greater Noida, UP, India © All rights are reserved by Kavita Khatana. *Corresponding Author: Kavita Khatana, Department of Chemistry, School of Basic and Applied Sciences, Galgotias University, Greater Noida, UP, India. Graphical Abstract Figure a Abstract Benzofuran and its derivatives are the major group amongst the natural collection of biologically active heterocyclic compounds. Their wide range of pharmacological activities and imaginable applications in medicinal and pharmaceutical chemistry have at- tracted various research scholars, medicinal chemists and pharmacologists. This review emphasizes the progress and development . ofKeywords: benzofuran Benzofuran; derivatives Antioxidant; in various biological Antiviral; activities Antimicrobial; with an Anticancer update of current research findings during a decade Introduction physiological and industrial world. In reference to pharmaceutical Heterocyclic ring systems have emerged as powerful scaf- industry, over 60% of the top retailing drugs contain at least one folds for many biological evaluations. Heterocyclic compounds heterocyclic motif as a part of overall topography of the compound. Benzofurans and its derivatives are important class of heterocyclic have significant role in medicinal and pharmacological chemistry, Citation: Kavita Khatana and Anjali Gupta. “An Update on Natural Occurrence and Biological Activity of Benzofurans”. Acta Scientific Medical Sciences 4.10 (2020): 114-123. An Update on Natural Occurrence and Biological Activity of Benzofurans 115 compounds, which are known to possess various biological proper- 3-(hydroxymethyl)-7-methoxy-2,3-dihydrobenzo furan-5-yl) ties.
    [Show full text]
  • Note N-Methyltyramine, a Gastrin-Releasing Factor in Beer, and Structurally Related Compounds As Agonists for Human Trace Amine-Associated Receptor 1
    _ Food Science and Technology Research, 26 (2), 313 317, 2020 Copyright © 2020, Japanese Society for Food Science and Technology http://www.jsfst.or.jp doi: 10.3136/fstr.26.313 Note N-Methyltyramine, a Gastrin-releasing Factor in Beer, and Structurally Related Compounds as Agonists for Human Trace Amine-associated Receptor 1 1,2* 1 1 1 3 3 Hiroto OHTA , Yuka MURAKAMI , Youhei TAKEBE , Kaori MURASAKI , Kenji OSHIMA , Hiroshi YOSHIHARA 1 and Shigeru MORIMURA 1Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami Chuo-ku, Kumamoto 860- 8555, Japan 2Department of Applied Microbial Technology, Faculty of Biotechnology and Life Science, Sojo University, 4-22-1 Ikeda Nishi-ku, Kumamoto 860-0082, Japan 3Department of Biological and Chemical Systems Engineering, National Institute of Technology, Kumamoto College, 2627 Hirayama-shinmachi, Yatsushiro, Kumamoto 866-8501, Japan Received September 30, 2019 ; Accepted December 5, 2019 N-Methyltyramine (N-MeTA) is known as a gastrin-releasing factor in beer. In this study, the agonistic actions of N-MeTA as well as tyramine (TA)/β-phenylethylamine (PEA) and their other N-methylated derivatives were examined to elucidate their structure-activity relationships, using a secreted placental alkaline phosphatase (SEAP)-based reporter assay in HEK-293 cells transiently expressing a G protein- coupled receptor, human trace amine-associated receptor 1 (hTAAR1). We detected the agonistic actions of six test compounds, including N-MeTA (EC50 = 6.78 µM), on hTAAR1. The agonistic actions were reduced depending on the number of N-methyl groups introduced into TA and PEA; the order of potency is PEA > N-methylphenylethylamine > TA ≈ N,N-dimethylphenylethylamine ≥ N-MeTA ≥ N,N-dimethyltyramine.
    [Show full text]
  • Cathinone-Derived Psychostimulants Steven J
    Review Cite This: ACS Chem. Neurosci. XXXX, XXX, XXX−XXX pubs.acs.org/chemneuro DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants Steven J. Simmons,*,† Jonna M. Leyrer-Jackson,‡ Chicora F. Oliver,† Callum Hicks,† John W. Muschamp,† Scott M. Rawls,† and M. Foster Olive‡ † Center for Substance Abuse Research (CSAR), Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 19140, United States ‡ Department of Psychology, Arizona State University, Tempe, Arizona 85281, United States ABSTRACT: Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These “synthetic cathinones” include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs.
    [Show full text]
  • Enantioselective Synthesis of (-)-Vallesine: Late- Stage C17-Oxidation Via Complex Indole Boronation
    Enantioselective synthesis of (-)-vallesine: late- stage C17-oxidation via complex indole boronation The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Antropow, Alyssa H., et al., "Enantioselective synthesis of (-)-vallesine: late-stage C17-oxidation via complex indole boronation." Organic Letters 20, 12 (2018): p. 3647-50 doi 10.1021/ acs.orglett.8b01428 ©2018 Author(s) As Published 10.1021/acs.orglett.8b01428 Publisher American Chemical Society (ACS) Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/125882 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Org Lett Manuscript Author . Author manuscript; Manuscript Author available in PMC 2019 June 15. Published in final edited form as: Org Lett. 2018 June 15; 20(12): 3647–3650. doi:10.1021/acs.orglett.8b01428. Enantioselective Synthesis of (−)-Vallesine: Late-stage C17- Oxidation via Complex Indole Boronation Alyssa H. Antropow, Nicholas R. Garcia, Kolby L. White, and Mohammad Movassaghi* Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Abstract The first enantioselective total synthesis of (−)-vallesine via a strategy that features a late-stage regioselective C17-oxidation, followed by a highly stereoselective transannular cyclization is reported. The versatility of this approach is highlighted by divergent synthesis of the archetypal alkaloid of this family, (+)-aspidospermidine, and an A-ring oxygenated derivative (+)- deacetylaspidospermine, the precursor to (−)-vallesine, from a common intermediate.
    [Show full text]
  • Effects of Acute Tyrosine/Phenylalanine Depletion on the Selective Processing of Smoking-Related Cues and the Relative Value of Cigarettes in Smokers
    Psychopharmacology DOI 10.1007/s00213-007-0995-5 ORIGINAL INVESTIGATION Effects of acute tyrosine/phenylalanine depletion on the selective processing of smoking-related cues and the relative value of cigarettes in smokers Brian Hitsman & James MacKillop & Anne Lingford-Hughes & Tim M. Williams & Faheem Ahmad & Sally Adams & David J. Nutt & Marcus R. Munafò Received: 16 May 2007 /Accepted: 18 October 2007 # Springer-Verlag 2007 Abstract tive mood, and expired carbon monoxide (CO) levels were Rationale Acute tyrosine/phenylalanine depletion (ATPD) is measured at various timepoints through 300 min. Participants a validated neurobiological challenge that results in reduced smoked at hourly intervals to prevent acute nicotine with- dopaminergic neurotransmission, allowing examination of drawal during testing. the effects of a hypodopaminergic state on craving-related Results The TYR/PHE-free mixture, as compared to the processes. BAL mixture, was associated with a greater increase in CO Objectives We studied 16 nonabstaining smokers (>10 levels from baseline ( p=0.01). Adjusting for the potential cigarettes/day; 9 males; age 20–33 years) to whom was confounding influence of between-condition differences in administered a tyrosine/phenylalanine-free mixture (TYR/ CO levels across time, TYR/PHE-free mixture was asso- PHE-free) and a balanced amino acid mixture (BAL) in a ciated with increased demand for cigarettes ( p=0.01) and double-blind, counterbalanced, crossover design. decreased attentional bias toward smoking-related words Methods Subjective cigarette craving, attentional bias to ( p=0.003). There were no significant differences between smoking-related word cues, relative value of cigarettes, nega- conditions in either subjective craving or depressed or anxious mood ( p values>0.05).
    [Show full text]