DOCSLIB.ORG

Tam Metin.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tam Metin.Pdf KARADENİZ TEKNİK ÜNİVERSİTESİ FEN BİLİMLERİ ENSTİTÜSÜ KİMYA ANABİLİM DALI PİRİMİDİN TÜREVİ BİLEŞİKLERİN KALKONLARDAN MİKRODALGA YÖNTEMİ İLE SENTEZİ VE BİYOLOJİK AKTİVİTELERİ DOKTORA TEZİ Yüksek Kimyager Seda FANDAKLI ŞUBAT 2016 TRABZON KARADENİZ TEKNİK ÜNİVERSİTESİ FEN BİLİMLERİ ENSTİTÜSÜ KİMYA ANABİLİM DALI PİRİMİDİN TÜREVİ BİLEŞİKLERİN KALKONLARDAN MİKRODALGA YÖNTEMİ İLE SENTEZİ VE BİYOLOJİK AKTİVİTELERİ Yüksek Kimyager Seda FANDAKLI Karadeniz Teknik Üniversitesi Fen Bilimleri Enstitüsünce “DOKTOR (KİMYA)” Unvanı Verilmesi İçin Kabul Edilen Tezdir. Tezin Enstitüye Verildiği Tarih : 29.12.2015 Tezin Savunma Tarihi : 12.02.2016 Tez Danışmanı : Prof. Dr. Nurettin YAYLI Trabzon - 2016 ÖNSÖZ Doktora Tezi olarak sunduğum bu çalışma Karadeniz Teknik Üniversitesi Araştırma Fonu (FHD-2016-5395) tarafından desteklenmiş olup, K.T.Ü. Fen Bilimleri Enstitüsü Kimya Anabilim Dalı’nda ve K.T.Ü. Sağlık Bilimleri Enstitüsü Eczacılık Fakültesin’de değerli hocam Sayın Prof. Dr. Nurettin YAYLI’nın araştırma laboratuarlarında gerçekleşmiştir. Doktora tez danışmanlığımı üstlenen, çalışmalarımın yürütülmesinde ve sonuçların değerlendirilmesinde benden tecrübe ve bilgilerini esirgemeyen ve bir doktora öğrencisi olarak sürekli bana araştırmanın, çalışmanın ve okumanın önemini vurgulayan değerli hocam Sayın Prof. Dr. Nurettin YAYLI’ya sonsuz teşekkürlerimi ve saygılarımı sunuyorum. Tez çalışmalarımı takip eden ve önerileri ile bana yol gösteren Sayın Prof. Dr. Şule BAHÇECİ ve Sayın Prof. Dr. Olcay BEKİRCAN hocalarıma teşekkür ederim ve saygılarımı sunarım. Biyolojik aktivite çalışmaları için Sayın Prof. Dr. Şengül Alpay KARAOĞLU ve Sayın Doç. Dr. Serdar ÜLKER hocalarıma teşekkür eder, saygılarımı sunarım. Çalışmalarımda; bilgi ve deneyimlerini benimle paylaşan Sayın Doç. Dr. Nuran KAHRİMAN, Sayın Doç. Dr. Ahmet YAŞAR ve Sayın Yrd. Doç. Dr. Asu Usta hocalarıma teşekkür ediyorum ve saygılarımı sunuyorum. Lisans, Yüksek lisans ve Doktora eğitimim boyunca bana emeği geçen Kimya Bölümü’nün değerli öğretim üyelerine, asistan arkadaşlarıma ve Eczacılık Fakültesi’nde beni yalnız bırakmayan bütün büyüklerime ve küçüklerime teşekkürlerimi ve saygılarımı sunuyorum. Kardeşliklerinden ve arkadaşlıklarından ötürü Arş. Gör. Büşra YAYLI, Arş. Gör. Nevin ULAŞ ve yüksek lisans öğrencileri Zeynep Ş. HAŞİMOĞLU, Vildan SERDAROĞLU ve Kıvanç PEKER’e teşekkür ediyorum. Maddi ve manevi sürekli desteklerini gördüğüm canım annem Havva FANDAKLI’ya, ablam Zeynep FANDAKLI’ya ve küçüğüm Eda FANDAKLI’ya ve tüm akrabalarıma sonsuz minnetlerimi sunuyorum. Yüksek Lisans ve Doktora eğitim kararını beraber aldığımız, hayatım boyunca kendisini her zaman saygıyla hatırlıyacağım, kanatsız bir melek olan rahmetli babam Mustafa FANDAKLI’ya yüce Allah’tan rahmet diliyorum. Seda FANDAKLI Trabzon, 2016 III TEZ ETİK BEYANNAMESİ Doktora Tezi olarak sunduğum “Pirimidin Türevi Bileşiklerin Kalkonlardan Mikrodalga Yöntemi İle Sentezi ve Biyolojik Aktiviteleri” başlıklı bu çalışmayı baştan sona kadar danışmanım Prof. Dr. Nurettin YAYLI’nın sorumluluğunda tamamladığımı, verileri kendim topladığımı, analizleri ilgili laboratuarlarda yaptığımı, başka kaynaklardan aldığım bilgileri metinde ve kaynakçada eksiksiz olarak gösterdiğimi, çalışma sürecinde bilimsel araştırma ve etik kurallara uygun olarak davrandığımı ve aksinin ortaya çıkması durumunda her türlü yasal sonucu kabul ettiğimi beyan ederim. 12/02/2016 Seda FANDAKLI IV İÇİNDEKİLER Sayfa No ÖNSÖZ ................................................................................................................................ III TEZ ETİK BEYANNAMESİ .............................................................................................. IV İÇİNDEKİLER ..................................................................................................................... V ÖZET ................................................................................................................................... XI SUMMARY ....................................................................................................................... XII ŞEKİLLER DİZİNİ .......................................................................................................... XIII TABLOLAR DİZİNİ ........................................................................................................ XIV SEMBOLLER DİZİNİ ..................................................................................................... XVI 1. GENEL BİLGİLER ............................................................................................ 1 1.1. Giriş .................................................................................................................... 1 1.2. Pirimidin ............................................................................................................. 2 1.2.1. Pirimidin Türevi Bileşiklerin Biyolojik Aktiviteleri .......................................... 3 1.2.2. Pirimidin Türevi Bileşiklerin Sentez Yöntemleri ............................................. 12 1.3. Kalkonlar .......................................................................................................... 14 1.3.1. Pirimidin Türevi Bileşiklerin Kalkon Bileşiklerinden Sentez Yöntemleri ........................................................................................................ 17 1.4. Mikrodalga ........................................................................................................ 25 1.4.1. Mikrodalganın Tarihçesi ................................................................................... 26 1.4.2. Mikrodalganın Teorisi ...................................................................................... 27 1.4.3. Mikrodalga Isıtma Mekanizmaları ................................................................... 28 1.4.3.1. Dipolar Polarizasyon ........................................................................................ 29 1.4.3.2. İyonik İletim Mekanizması ............................................................................... 29 1.4.4. Mikrodalga Destekli Reaksiyonlar ................................................................... 30 1.4.4.1. Çözücü Varlığında (Polar ya da Apolar ) Gerçekleşen Reaksiyonlar .............. 30 1.4.4.2. Geri soğutucu Altında Gerçekleşen Reaksiyonlar ............................................ 30 1.4.4.3. Basınç Altında Gerçekleşen Reaksiyonlar........................................................ 31 1.4.5. Katı-Faz Reaksiyonları ..................................................................................... 32 1.4.5.2. Çözücü, Katalizör ya da Mineralin Kullanılmadığı Reaksiyonlar.................... 34 1.4.5.3. Faz Transfer Katalizörleri (FTK) ile Gerçekleşen Reaksiyonlar ...................... 34 1.4.6. Mikrodalga Reaksiyonlarında Kullanılan Açık ve Kapalı Kaplar .................... 34 V 1.4.8. Mikrodalga Reaksiyonlarda Sıcaklık ve Zaman ............................................... 35 1.4.9. Mikrodalga Destekli Organik Sentezlerin Klasik Yöntemden Üstünlükleri ...................................................................................................... 36 1.5. Spektroskopi ..................................................................................................... 37 1.6. Kromatografi .................................................................................................... 38 1.6.1. PİTK (Preparatif İnce Tabaka Kromatografisi) ................................................ 38 1.6.1.1. Preparatif İnce Tabaka Kromatografisinin Uygulanması ................................. 38 1.6.2. Kolon Kromatografisi ....................................................................................... 39 1.6.2.1. Kolon Kromatografisinin Uygulanması ........................................................... 40 1.7. Antimikrobiyal Etki .......................................................................................... 41 1.8. Enzimatik İnhibitörler ....................................................................................... 42 1.8.1. Lipaz ................................................................................................................. 42 1.8.2. Alfa-Glukozidaz ............................................................................................... 42 2. YAPILAN ÇALIŞMALAR .............................................................................. 44 2.1. Çözücüler ve Kimyasallar ................................................................................ 44 2.2. Enstrümentasyon .............................................................................................. 44 2.3. 166-184 Nolu Bileşiklerin Sentezlenmesi ........................................................ 45 2.3.1. (2E)-1-(2-Metoksifenil)-3-fenilprop-2-en-1-on (166) Nolu Bileşiğinin Sentezi .............................................................................................................. 45 2.3.2. (2E)-1,3-Bis(2-metoksifenil)prop-2-en-1-on (167) Nolu Bileşiğinin Sentezi .............................................................................................................. 46 2.3.3. (2E)-1-(2-Metoksifenil)-3-(3-metoksifenil)prop-2-en-1-on (168) Nolu Bileşiğinin Sentezi ............................................................................................ 47 2.3.4. (2E)-1-(2-Metoksifenil)-3-(4-metoksifenil)prop-2-en-1-on (169) Nolu Bileşiğinin Sentezi ............................................................................................ 48 2.3.5. (2E)-3-(2,3-Dimetoksifenil)-1-(2-metoksifenil)prop-2-en-1-on
Load more

Recommended publications
  • Phytochem Referenzsubstanzen
    High pure reference substances Phytochem Hochreine Standardsubstanzen for research and quality für Forschung und management Referenzsubstanzen Qualitätssicherung Nummer Name Synonym CAS FW Formel Literatur 01.286. ABIETIC ACID Sylvic acid [514-10-3] 302.46 C20H30O2 01.030. L-ABRINE N-a-Methyl-L-tryptophan [526-31-8] 218.26 C12H14N2O2 Merck Index 11,5 01.031. (+)-ABSCISIC ACID [21293-29-8] 264.33 C15H20O4 Merck Index 11,6 01.032. (+/-)-ABSCISIC ACID ABA; Dormin [14375-45-2] 264.33 C15H20O4 Merck Index 11,6 01.002. ABSINTHIN Absinthiin, Absynthin [1362-42-1] 496,64 C30H40O6 Merck Index 12,8 01.033. ACACETIN 5,7-Dihydroxy-4'-methoxyflavone; Linarigenin [480-44-4] 284.28 C16H12O5 Merck Index 11,9 01.287. ACACETIN Apigenin-4´methylester [480-44-4] 284.28 C16H12O5 01.034. ACACETIN-7-NEOHESPERIDOSIDE Fortunellin [20633-93-6] 610.60 C28H32O14 01.035. ACACETIN-7-RUTINOSIDE Linarin [480-36-4] 592.57 C28H32O14 Merck Index 11,5376 01.036. 2-ACETAMIDO-2-DEOXY-1,3,4,6-TETRA-O- a-D-Glucosamine pentaacetate 389.37 C16H23NO10 ACETYL-a-D-GLUCOPYRANOSE 01.037. 2-ACETAMIDO-2-DEOXY-1,3,4,6-TETRA-O- b-D-Glucosamine pentaacetate [7772-79-4] 389.37 C16H23NO10 ACETYL-b-D-GLUCOPYRANOSE> 01.038. 2-ACETAMIDO-2-DEOXY-3,4,6-TRI-O-ACETYL- Acetochloro-a-D-glucosamine [3068-34-6] 365.77 C14H20ClNO8 a-D-GLUCOPYRANOSYLCHLORIDE - 1 - High pure reference substances Phytochem Hochreine Standardsubstanzen for research and quality für Forschung und management Referenzsubstanzen Qualitätssicherung Nummer Name Synonym CAS FW Formel Literatur 01.039.
    [Show full text]
  • Influência De Chalconas Análogas, Xantonas E Monossacarídeos Na Glicemia Em Modelo Experimental Animal
    ELGA HELOISA ALBERTON INFLUÊNCIA DE CHALCONAS ANÁLOGAS, XANTONAS E MONOSSACARÍDEOS NA GLICEMIA EM MODELO EXPERIMENTAL ANIMAL FLORIANÓPOLIS 2007 Elga Heloisa Alberton INFLUÊNCIA DE CHALCONAS ANÁLOGAS, XANTONAS E MONOSSACARÍDEOS NA GLICEMIA EM MODELO EXPERIMENTAL ANIMAL Dissertação apresentada ao curso de Pós-graduação em Farmácia da Universidade Federal de Santa Catarina, como requisito parcial para o título de Mestre em Farmácia. Área de concentração: Análises Clínicas . Orientadora: Profa. Dra. Fátima Regina Mena Barreto Silva Florianópolis 2007 ALBERTON, Elga Heloisa Influência de chalconas análogas, xantonas e monossacarídeos na glicemia em modelo experimental animal/Elga Heloisa Alberton. Flrianópolis, 2006. //p. Dissertação (Mestrado) – Universidade Federal de Santa Catarina. Programa de pós Graduação em Farmácia 1. Diabetes. 2. Ácido glicônico. 3. Ácido tatárico. 4. Polygala paniculata. 5. Polygala cyparissias. 6. Xantonas. 7. Chalconas. “INFLUÊNCIA DE CHALCONAS ANÁLOGAS, XANTONAS E MONOSSACARÍDEOS NA GLICEMIA EM MODELO EXPERIMENTAL ANIMAL” POR ELGA HELOISA ALBERTON Dissertação julgada e aprovada em sua forma final pelo Orientador e membros da Banca Examinadora, composta pelos Professores Doutores: Banca Examinadora: ____________________________________ Adair Roberto Soares dos Santos (UFSC) ____________________________________ Danilo Wilhelm Filho (UFSC) ____________________________________ Maria Rosa Chitolina Schetinger (UFSM-RS) Florianópolis, 12 de fevereiro de 2007. Dedico este trabalho aos meus pais, Hercílio C. Alberton e Alba R. Lopes Minatto, pela oportunidade recebida e, que por vezes tão longe fisicamente, estiveram sempre, através de seu carinho e apoio, presentes em todos os momentos da minha vida. AGRADECIMETOS A DEUS por me conceder a oportunidade de realizar mais um sonho. Agradecimento especial à minha orientadora Profa. Dra. Fátima Regina Mena Barreto Silva, pela confiança em mim depositada.
    [Show full text]
  • From Alpinia Zerumbet: Its Isolation, Synthesis, and Characterization
    Molecules 2015, 20, 16306-16319; doi:10.3390/molecules200916306 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Dihydro-5,6-dehydrokavain (DDK) from Alpinia zerumbet: Its Isolation, Synthesis, and Characterization Tran Dang Xuan 1 and Rolf Teschke 2,* 1 Division of Development Technology, Graduate School for International Development and Cooperation (IDEC), Hiroshima University, Higashi Hiroshima 739-8529, Japan; E-Mail: [email protected] 2 Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Academic Teaching Hospital of the Medical Faculty of the Goethe University, Frankfurt/Main, 63450 Hanau, Germany * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +49-6181-218-59; Fax: +49-6181-296-4211. Academic Editor: Derek J. McPhee Received: 9 June 2015 / Accepted: 20 August 2015 / Published: 9 September 2015 Abstract: Dihydro-5,6-dehydrokavain (DDK) is the major and most promising component of the tropical plant Alpinia zerumbet (shell ginger), a species of the ginger family Zingiberaceae. Alpinia zerumbet is known for its human use as a traditional herbal medicine, food, and dietary supplement. With its α-lactone ring, DDK belongs to the large chemical group of kavalactones, which are also found in kava (Piper methysticum), another herbal medicine; DDK is characterized by a double-bond linkage at positions 5,6 and the absence of a double-bond linkage at positions 7,8. This dissociates DDK from other kavalactones with their linkages at positions 7,8 and 5,6 that are both either completely saturated or unsaturated, or may have an unsaturated bond at the position 7,8 as well as a saturated bond at the position 5,6.
    [Show full text]
  • The Biosynthetic Origin of Psychoactive Kavalactones in Kava
    bioRxiv preprint doi: https://doi.org/10.1101/294439; this version posted April 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The biosynthetic origin of psychoactive kavalactones in kava 1 1 1,2 1,2 Tomáš Pluskal ,​ Michael P. Torrens-Spence ,​ Timothy R. Fallon ,​ Andrea De Abreu ,​ ​ ​ ​ ​ 1,2 1,2, Cindy H. Shi ,​ and Jing-Ke Weng *​ ​ ​ 1 Whitehead​ Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142 USA. 2 Department​ of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA. *Corresponding author. Email: [email protected] ​ 1 bioRxiv preprint doi: https://doi.org/10.1101/294439; this version posted April 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract For millennia, humans have used plants for medicinal purposes. However, our limited understanding of plant biochemistry hinders the translation of such ancient wisdom into modern 1 pharmaceuticals .​ Kava (Piper methysticum) is a medicinal plant native to the Polynesian islands ​ ​ ​ with anxiolytic and analgesic properties supported by over 3,000 years of traditional use as well 2–5 as numerous recent clinical trials .​ The main psychoactive principles of kava, kavalactones, are ​ a unique class of polyketide natural products known to interact with central nervous system through mechanisms distinct from those of the prescription psychiatric drugs benzodiazepines 6,7 and opioids .​ Here we report de novo elucidation of the biosynthetic pathway of kavalactones, ​ ​ ​ consisting of seven specialized metabolic enzymes.
    [Show full text]
  • WO 2018/002916 Al O
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/002916 Al 04 January 2018 (04.01.2018) W !P O PCT (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C08F2/32 (2006.01) C08J 9/00 (2006.01) kind of national protection available): AE, AG, AL, AM, C08G 18/08 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, PCT/IL20 17/050706 HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (22) International Filing Date: KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 26 June 2017 (26.06.2017) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 246468 26 June 2016 (26.06.2016) IL kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (71) Applicant: TECHNION RESEARCH & DEVEL¬ UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, OPMENT FOUNDATION LIMITED [IL/IL]; Senate TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, House, Technion City, 3200004 Haifa (IL).
    [Show full text]
  • Standard Format for AOAC Standard Method Performance Requirement
    1 DRAFT AOAC SMPR 2017.XXX; Version 11.17.2017 2 3 Method Name: Determination of Kavalactones and/or Flavokavains from Kava (Piper 4 methysticum) 5 6 Approved by: Stakeholder Panel on Dietary Supplements (SPDS) 7 8 Intended Use: For quality assurance and compliance to current good manufacturing practices. 9 10 1. Purpose: 11 AOAC SMPRs describe the minimum recommended performance characteristics to be used 12 during the evaluation of a method. The evaluation may be an on-site verification, a single- 13 laboratory validation, or a multi-site collaborative study. SMPRs are written and adopted by 14 AOAC Stakeholder Panels composed of representatives from the industry, regulatory 15 organizations, contract laboratories, test kit manufacturers, and academic institutions. 16 AOAC SMPRs are used by AOAC Expert Review Panels in their evaluation of validation study 17 data for method being considered for Performance Tested Methods or AOAC Official 18 Methods of Analysis, and can be used as acceptance criteria for verification at user 19 laboratories. [Refer to Appendix F: Guidelines for Standard Method Performance 20 Requirements, Official Methods of Analysis of AOAC INTERNATIONAL (2012) 20th Ed., AOAC 21 INTERNATIONAL, Gaithersburg, MD, USA.] 22 23 2. Applicability: 24 Identification and quantitation of the six major kavalactones (desmethoxyyangonin, 25 dihydrokavain, yangonin, kavain, dihydromethysticin, and methysticin) and/or flavokavains 26 A, B, and C (see table 1 for more detailed information on analytes and figure 1 for molecular 27 structures) derived from the underground portions of kava (Piper methysticum) in plant 28 material, dietary ingredients and dietary supplements as listed table 2. Methods will be 29 accepted that identify and quantify either flavokavains and/or kavalactones.
    [Show full text]
  • Biological Activity, Hepatotoxicity, and Structure-Activity Relationship Of
    Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 6851798, 14 pages https://doi.org/10.1155/2021/6851798 Review Article Biological Activity, Hepatotoxicity, and Structure-Activity Relationship of Kavalactones and Flavokavins, the Two Main Bioactive Components in Kava (Piper methysticum) Yingli Wang , Chao Su , Bo Zhang , Yang Niu , Ruru Ren , Xiaojun Zhao , Lingling Yang , Wannian Zhang , and Xueqin Ma Department of Pharmaceutical Analysis, School of Pharmacy, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, 1160 Shenli Street, Yinchuan 750004, China Correspondence should be addressed to Xueqin Ma; [email protected] Received 11 June 2021; Accepted 13 August 2021; Published 23 August 2021 Academic Editor: Daniela Rigano Copyright © 2021 Yingli Wang et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Kava (Piper methysticum Forst) is a popular and favorable edible medicinal herb which was traditionally used to prepare a nonfermented beverage with relaxant beneficial for both social and recreational purposes. Numerous studies conducted on kava have confirmed the presence of kavalactones and flavokawains, two major groups of bioactive ingredients, in this miraculous natural plant. Expectedly, both kavalactone and flavokawain components exhibited potent antianxiety and anticancer activities,
    [Show full text]
  • Kavalactones and Flavokavains in Piper Methysticum (Kava)
    Original Papers Single-Lab Validation for Determination of Kavalactones and Flavokavains in Piper methysticum (Kava) Authors Ying Liu1,JensenA.Lund2,SusanJ.Murch2, Paula N. Brown 1 Affiliations ABSTRACT 1 Natural Health and Food Products Research Groups, Piper methysticum (Kava) is a plant whose roots are used in the BC Institute of Technology preparation of traditional beverages with spiritual, medicinal, 2 DepartmentofChemistry,UniversityofBritishColumbia and social importance for the Pacific Islanders. Kava is also sold as a herbal supplement or recreational beverage con- Key words sumed for its mild inebriating effect in Europe and North ‑ kava, Piper methysticum, kavalactones, flavokavains, HPLC UV, America. With an ongoing interest in the safety and quality ‑ single laboratory validation, Piperaceae, quality control of kava products, it is necessary to develop a validated meth- od for determination of kava chemical composition to ensure received March 13, 2018 confidence in quality assessment. Thus, an high-performance revised May 16, 2018 liquid chromatography with ultraviolet detection (HPLC-UV) accepted May 27, 2018 method was developed, optimized, and validated for deter- Bibliography mining six major kavalactones and three flavokavains in kava DOI https://doi.org/10.1055/a-0637-2400 raw materials and finished products based on AOAC single- Published online June 25, 2018 | Planta Med 2018; 84: 1213– laboratory validation guidelines. This is the first fully validated 1218 © Georg Thieme Verlag KG Stuttgart · New York | analytical method for measuring kavalactones and flavoka- ISSN 0032‑0943 vains in a single run. The separation of the analytes was achieved in 10 min with an Agilent Poroshell C18 column us- Correspondence ing gradient separation.
    [Show full text]
  • The Biosynthetic Origin of Psychoactive Kavalactones in Kava
    The biosynthetic origin of psychoactive kavalactones in kava 1 1 1,2 1,2 Tomáš Pluskal ,​ Michael P. Torrens-Spence ,​ Timothy R. Fallon ,​ Andrea De Abreu ,​ ​ ​ ​ ​ 1,2 1,2,* Cindy H. Shi ,​ and Jing-Ke Weng ​ ​ 1 Whitehead​ Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142 USA. 2 Department​ of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA. * Corresponding​ author. Email: [email protected] ​ Kava (Piper methysticum) is an ethnomedicinal shrub native to the Polynesian islands with ​ ​ well-established anxiolytic and analgesic properties. Its main psychoactive principles, kavalactones, form a unique class of polyketides that interact with the human central nervous system through mechanisms distinct from those of conventional psychiatric drugs. However, an unknown biosynthetic machinery and difficulty in chemical synthesis hinder the therapeutic use of kavalactones. In addition, kava contains several chalconoids with reported anti-cancer properties, known as flavokavains. Here, we report de novo ​ elucidation of key components of the kavalactone and flavokavain biosynthetic network, encompassing eight specialized metabolic enzymes. We present the structural basis for the evolutionary development of a pair of paralogous styropyrone synthases that establish the kavalactone scaffold as well as the catalytic mechanism of a regio- and stereo-specific kavalactone reductase that produces a subset of chiral kavalactones. We further demonstrate the feasibility of engineering kavalactone production
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2005/0037025A1 GOW Et Al
    US 20050O37025A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0037025A1 GOW et al. (43) Pub. Date: Feb. 17, 2005 (54) METHODS AND COMPOSITIONS Continuation-in-part of application No. 10/408,900, COMPRISING KAVA AND MATE OR filed on Apr. 8, 2003. THEOBROMINE Continuation-in-part of application No. 10/273,981, filed on Oct. 18, 2002. (76) Inventors: Robert T. Gow, Naples, FL (US); John Pierce, Thousand Oaks, CA (US); (60) Provisional application No. 60/514,187, filed on Oct. George W. Sypert, Naples, FL (US) 24, 2003. Correspondence Address: Publication Classification TROUTMAN SANDERS LLP BANK OF AMERICA PLAZA, SUITE 5200 (51) Int. Cl." ........................ A61K 35/78; A61K 31/366 600 PEACHTREE STREET, NE (52) U.S. Cl. ..................... 424/195.18; 424/734; 514/460 ATLANTA, GA 30308-2216 (US) (57) ABSTRACT (21) Appl. No.: 10/945,108 The present invention comprises compositions comprising (22) Filed: Sep. 20, 2004 combinations of compositions of extracts of kava mate extract compositions or theobromine. The invention further Related U.S. Application Data comprises methods for treating conditions related to mental and physical fatigue, anxiety, muscle tension, nervous (63) Continuation-in-part of application No. 10/263,579, depression, headache, obesity, and mild pain as well a filed on Oct. 3, 2002. enhancement of cognition and mental focus comprising Continuation-in-part of application No. 10/273,943, administering effective amounts of the compositions of the filed on Oct. 18, 2002. present invention. US 2005/0037025 A1 Feb. 17, 2005 METHODS AND COMPOSITIONS COMPRISING mate beverage is Such a part of the Social Structure and KAVA AND MATE OR THEOBROMINE cultural habits of So many people and the fact that it is being increasingly used as a nutraceutical medicinal agent, reduc CROSS-REFERENCE TO RELATED ing the amount of mate consumed does not appear to be a APPLICATIONS viable method for reducing caffeine consumption.
    [Show full text]
  • Dietary Chalcones with Chemopreventive and Chemotherapeutic Potential
    Genes Nutr (2011) 6:125–147 DOI 10.1007/s12263-011-0210-5 RESEARCH PAPER Dietary chalcones with chemopreventive and chemotherapeutic potential Barbora Orlikova • Deniz Tasdemir • Frantisek Golais • Mario Dicato • Marc Diederich Received: 23 July 2010 / Accepted: 6 January 2011 / Published online: 4 February 2011 Ó Springer-Verlag 2011 Abstract Chalcones are absorbed in the daily diet and Introduction appear to be promising cancer chemopreventive agents. Chalcones represent an important group of the polyphenolic Polyphenols represent one of the most prevalent classes of family, which includes a large number of naturally occurring compounds found in our daily diet [171]. Over the last ten molecules. This family possesses an interesting spectrum of years, increasing attention has been dedicated to chalcones biological activities, including antioxidative, antibacterial, because of their interesting biological activities. Indeed, anti-inflammatory, anticancer, cytotoxic, and immuno- chalcones constitute an important group of natural com- suppressive potential. Compounds of this family have been pounds that are especially abundant in fruits (e.g., citruses, shown to interfere with each step of carcinogenesis, apples), vegetables (e.g., tomatoes, shallots, bean sprouts, including initiation, promotion and progression. Moreover, potatoes) and various plants and spices (e.g., licorice),— numerous compounds from the family of dietary chalcones many of which have been used for centuries in traditional appear to show activity against cancer cells, suggesting that herbal medicine [29]. Chemically, chalcones are open- these molecules or their derivatives may be considered as chain flavonoids bearing two aromatic rings linked by a potential anticancer drugs. This review will focus primarily three-carbon enone moiety (Fig. 1).
    [Show full text]
  • Identification, Analysis and Manipulation of the Torrubiellone a Gene Cluster
    IDENTIFICATION, ANALYSIS AND MANIPULATION OF THE TORRUBIELLONE A GENE CLUSTER By GUILLERMO CARLOS FERNANDEZ BUNSTER School of Biological Sciences University of Bristol United Kingdom A dissertation submitted to the UNIVERSITY OF BRISTOL in accordance with the requirements of the DOCTOR OF PHILOSOPHY in the FACULTY OF SCIENCE June / December 2016 Word count = 43.800 i Abstract Torrubiellones A-D, extracted from Torrubiella sp. BCC2165, are structurally similar to 2- pyridone compounds. Torrubiellone A is particularly interesting because it has antimalarial activity. Combining knowledge of the gene clusters responsible for the biosynthesis of the structurally similar compounds with in-silico analysis of the Torrubiella genome sequence lead to the identification of the torrubiellone A biosynthetic gene cluster. Torrubiella sp. BCC2165 DNA was extracted, sequenced and analysed to reveal a putative torrubiellone A gene cluster, comprising torS encoding a hybrid polyketide synthase- nonribosomal peptide synthetase, torA and torB encoding two P450 cytochromes and torC encoding an enoyl reductase. Comparison to the tenellin and desmethylbassianin gene clusters identified two additional genes, torD and torE, which could be responsible for structural differences between torrubiellone A and desmethylbassianin. torS was assembled without introns by homologous recombination in yeast and combined with other biosynthetic genes from the putative torrubiellone cluster, on a multigene expression vector. Assembled plasmids were used to transform the filamentous fungus Aspergillus oryzae NSAR1, yielding strongly yellow-pigmented transformants. Analysis of organic extracts from transformants by liquid chromatography-mass spectroscopy indicated that the production of torrubiellone- related compounds has been achieved. torD and torE gene functions were investigated by co- expressing these genes in a tenellin-producing A.
    [Show full text]