uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Cascade synthesis with (triphenylphosphoranylidene)ethenone as a versatile reagent for fast synthesis of heterocycles and unsaturated amides under microwave dielectric heating
Personal Chemistry AB.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
2002 (English)In: Combinatorial chemistry & high throughput screening, ISSN 1386-2073, Vol. 5, no 7, 571-574 p.Article in journal (Refereed) Published
Abstract [en]

A general procedure for the synthesis of a large variety of compounds comprising an alpha, beta-unsaturated carbonyl functionality was developed. The use of one-pot cascade synthesis with (triphenylphosphoranylidene)ethenone as a versatile reagent for various formations including heterocycles of different ring sizes and unsaturated amides in combination with microwave dielectric heating is described. The method was used to synthesize a small library of unsaturated amides.

Place, publisher, year, edition, pages
2002. Vol. 5, no 7, 571-574 p.
Keyword [en]
microwave heating, one-pot synthesis, cascade reaction, library synthesis, (triphenylphosphoranylidene)ethenone, organic-synthesis, cumulated ylides, chemistry
National Category
Organic Chemistry
URN: urn:nbn:se:uu:diva-100964ISI: 000181710400008PubMedID: 12470270ISBN: 1386-2073OAI: oai:DiVA.org:uu-100964DiVA: diva2:211425
Available from: 2009-04-14 Created: 2009-04-14 Last updated: 2010-11-23Bibliographically approved
In thesis
1. On the Versatility of Microwave-Assisted Chemistry: Exemplified by Applications in Medicinal Chemistry, Heterocyclic Chemistry and Biochemistry
Open this publication in new window or tab >>On the Versatility of Microwave-Assisted Chemistry: Exemplified by Applications in Medicinal Chemistry, Heterocyclic Chemistry and Biochemistry
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Today, the demand for speed in drug discovery is constantly increasing, particularly in the iterative processes of hit validation and expansion and lead optimization. Irradiation with microwaves (MWs) has been applied in the area of organic synthesis to accelerate chemical reactions and to facilitate the generation of new chemical entities since 1986. In the work presented in this thesis, the use of MW-mediated heating has been expanded to address three fields of drug discovery, namely hit expansion, chemical library generation and genomics.

In the first project, potential inhibitors of malaria aspartic proteases were designed and synthesized, partly by MW-assisted organic chemistry, and evaluated with regard to their inhibitory efficacy on five malaria aspartic proteases and their selectivity over two human aspartic proteases. The synthetic work included the development of fast and convenient methods of MW-assisted formation of thiazolidines and epoxy esters. Some of the resulting structures proved to be efficacious inhibitors of the aspartic protease that degrades haemoglobin in all four malaria parasites infecting man. No inhibitor affected the human aspartic proteases.

Expedient, two-step, single-operation synthetic routes to heterocycles of medicinal interest were developed in the second and third projects. In the former, the use of a versatile synthon, Ph3PCCO, provided α,β-unsaturated lactones, lactams and amides within 5–10 minutes. In the latter project, saturated lactams were formed from amines and lactones in 35 minutes, in the absence of strong additives. These two MW-mediated protocols allowed the reduction of the reaction time from several hours or days to minutes.

In the fourth project, a fully automated MW-assisted protocol for the important enzyme-catalysed polymerase chain reaction (PCR) was established. In addition, the PCR reaction could be performed in unusually large volumes, 2.5 mL and 15 mL, with yields corresponding to those from conventional PCR. Good amplification rates suggested that the thermophilic enzyme, Taq polymerase, was not affected by the MW radiation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 109 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 100
microwave-assisted chemistry, malaria, aspartic protease, plasmepsin, PfPM4, PmPM4, PoPM4, PvPM4, inhibitor, unsaturated lactone, unsaturated lactam, unsaturated amide, lactam, Bestmann's ylide, ionic liquid, polymerase chain reaction, thermophilic enzyme
National Category
Medicinal Chemistry Organic Chemistry Biochemistry and Molecular Biology
Research subject
urn:nbn:se:uu:diva-101356 (URN)978-91-554-7535-2 (ISBN)
Public defence
2009-06-12, B22, Biomedical Centre (BMC), Husargatan 3, Uppsala, 09:15 (English)
Available from: 2009-05-20 Created: 2009-04-23 Last updated: 2009-05-20Bibliographically approved

Open Access in DiVA

No full text

By organisation
Organic Pharmaceutical Chemistry
In the same journal
Combinatorial chemistry & high throughput screening
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 194 hits
ReferencesLink to record
Permanent link

Direct link