uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Synthesis of 4H-Benzo[e][1,3]oxazin-4-ones by a Carbonylation-Cyclization Domino Reaction of ortho-Halophenols and Cyanamide
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.ORCID-id: 0000-0002-3600-0497
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
2017 (Engelska)Ingår i: ChemistryOpen, ISSN 2191-1363, Vol. 6, nr 5, s. 620-628Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

A mild and convenient one-step preparation of 4H-1,3-benzoxazin-4-ones by a domino carbonylation-cyclization process is developed. Readily available ortho-iodophenols are subjected to palladium-catalyzed carbonylative coupling with Mo(CO)(6) and cyanamide, followed by a spontaneous, intramolecular cyclization to afford 4H-1,3-benzaxazin-4-ones in moderate to excellent yields. Furthermore, the scope of the reaction is ex tended to include challenging orthobromophenols. Finally, to highlight the versatility of the developed method, Mo(CO), is successfully replaced with a wide array of CO-releasing reagents, such as oxalyl chloride, phenyl formate, 9-methylfluorene-9-carbonyl chloride, and formic acid, making this an appealing strategy for the synthesis of 4H-benzo[e][1,3]oxazin-4-ones.

Ort, förlag, år, upplaga, sidor
2017. Vol. 6, nr 5, s. 620-628
Nationell ämneskategori
Organisk kemi
Identifikatorer
URN: urn:nbn:se:uu:diva-329967DOI: 10.1002/open.201700130ISI: 000413038400003PubMedID: 29046856OAI: oai:DiVA.org:uu-329967DiVA, id: diva2:1143964
Tillgänglig från: 2017-09-24 Skapad: 2017-09-24 Senast uppdaterad: 2018-02-05Bibliografiskt granskad
Ingår i avhandling
1. Palladium(0)-Catalysed Carbonylative Multicomponent Reactions: Synthesis of Heterocycles and the Application of Quinolinyl Pyrimidines as Enzyme Inhibitors
Öppna denna publikation i ny flik eller fönster >>Palladium(0)-Catalysed Carbonylative Multicomponent Reactions: Synthesis of Heterocycles and the Application of Quinolinyl Pyrimidines as Enzyme Inhibitors
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Palladium-catalysed carbonylative multicomponent reactions have proven useful for the synthesis of structurally diverse compounds. Carbon monoxide serves as an atom-efficient, one-carbon building block, which allows for further structural elaboration of the carbonyl compound. By varying the components of the carbonylative multicomponent reaction, considerable product diversity can readily be attained. However, due to the reluctance to use toxic CO gas, considerable efforts have been directed at exploring non-gaseous approaches. The work described in this thesis has mainly focused on the development of palladium(0)-catalysed, carbonylative multicomponent synthetic methodology, using the non-gaseous CO source molybdenum hexacarbonyl, in the synthesis of heterocycles and other biologically relevant functional groups.

The first part of this work describes the development of a non-gaseous carbonylative Sonogashira cross-coupling of bifunctional ortho-iodoanilines and terminal alkynes. Where 4-quinolones were synthesised via a carbonylation/cyclisation sequence. Using a similar synthetic strategy, three different N-cyanobenzamide intermediates were prepared by palladium-catalysed carbonylative couplings of various aryl halides and bromides and cyanamide. The formed intermediates provided a basis for further chemical transformations. First, ortho-iodoanilines were carbonylatively coupled with cyanamide and subsequently cyclised to yield heterocyclic 2-aminoquinazolinones. Next, building on those findings, the same synthetic strategy was applied to ortho-halophenols to provide a highly convenient domino carbonylation/cyclisation method for the preparation of benzoxazinones. The developed method was used to evaluate the efficiency of various non-gaseous CO sources. Third, the palladium-catalysed carbonylative synthesis of N-cyanobenzamides, was used to produce biologically relevant N-acylguanidines with considerable product diversity. Finally, one of the developed carbonylative methodologies was used in the preparation of potential NDH-2 inhibitors based on a quinolinyl pyrimidine scaffold. The prepared compounds were biologically evaluated in terms of inhibition of oxidoreductase NDH-2 and antibacterial activity on Gram-negative bacteria, S. aureus and Mtb. The biological evaluation revealed that some of the quinolinyl pyrimidines exerted inhibitory activity on the NDH-2 enzyme and possessed antibacterial properties.

The work described in this thesis has been devoted to the development of non-gaseous one-pot, multicomponent carbonylation/cyclisation and carbonylation/amination reactions. The described methods offer highly attractive synthetic strategies that can be of great value to synthetic and medicinal chemists.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2017. s. 86
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 237
Nyckelord
Palladium catalysis, Carbonylation, Multicomponent reactions, Domino reactions, Heterocycles, 4-Quinolones, 2-Aminoquinazolinones, Benzoxazinones, N-Acylguanidines, Type II NADH dehydrogenase, NDH-2
Nationell ämneskategori
Organisk kemi Läkemedelskemi
Identifikatorer
urn:nbn:se:uu:diva-329970 (URN)978-91-513-0083-2 (ISBN)
Disputation
2017-11-10, B41, BMC, Husargatan 3, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2017-10-20 Skapad: 2017-09-24 Senast uppdaterad: 2018-01-13

Open Access i DiVA

fulltext(463 kB)63 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 463 kBChecksumma SHA-512
e7c67829bbb61591b1dd7862318fd5ea7d0a184ec11d7daff34570c8f89da67b61ddc425b60f716cf2d5cc14dedc1cff6fc177ad05e1e6a9bb0c65c89e7f61cc
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Åkerbladh, LindaChow, Shiao Y.Odell, Luke R.Larhed, Mats

Sök vidare i DiVA

Av författaren/redaktören
Åkerbladh, LindaChow, Shiao Y.Odell, Luke R.Larhed, Mats
Av organisationen
Avdelningen för organisk farmaceutisk kemiInstitutionen för läkemedelskemiScience for Life Laboratory, SciLifeLab
I samma tidskrift
ChemistryOpen
Organisk kemi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 63 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 128 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf