Synthesis of bioactive natural products and analogues
(2014)- Abstract
- Natural products have until recently provided the only remedy for treatment of diseases. The development of modern chemistry in the last centuries has opened the door for tapping into the chemical diversity found in nature. Synthetic natural products, together with analogues, are an important piece in the puzzle towards curing many ailments. In this thesis, synthetic endeavors towards different biological targets are presented.
A plant derived cannabinoid was synthesized and shown to have nociceptive properties in mice, by activating the TRPA1 receptors in the spinal cord, without having any activity on the cannabinoid receptors.
Chronic obstructive pulmonary disease (COPD) is a growing health problem and the... (More) - Natural products have until recently provided the only remedy for treatment of diseases. The development of modern chemistry in the last centuries has opened the door for tapping into the chemical diversity found in nature. Synthetic natural products, together with analogues, are an important piece in the puzzle towards curing many ailments. In this thesis, synthetic endeavors towards different biological targets are presented.
A plant derived cannabinoid was synthesized and shown to have nociceptive properties in mice, by activating the TRPA1 receptors in the spinal cord, without having any activity on the cannabinoid receptors.
Chronic obstructive pulmonary disease (COPD) is a growing health problem and the cytokine thymic stromal lymphopoietin (TSLP) has been shown to play a key role. By semisynthesis of TSLP inhibitors, a structure activity relationship study was performed in order to find new TSLP inhibitors, which leave the bodily defense systems intact, and help persons with asthma or COPD.
Parasitic illnesses often lack efficient treatments, thus a total synthesis of pulchrol and pulchral, natural antiprotozoal benzochromenes, and the preparation of a library of analogues for a SAR study, is presented. Furthermore, a synthetic effort towards the total synthesis of the plant metabolite pulcaffeate is presented, a compound that also has been shown to possess antiprotozoal activity.
By targeting different biological systems, new compounds are developed and tested, In the case of the synthesis of the bioactive benzochromenes, this led to the finding of a method for synthesizing either benzochromene or fluorene compounds from a common starting material. This could possibly be of interest for the synthetic organic chemists in the future. (Less) - Abstract (Swedish)
- Popular Abstract in Swedish
I flera tusentals år har människan använt sig av naturen till hjälp för att bota åkommor och krämpor. Det som hon har dragit nytta av då är att alla växter och plantor producerar flertalet små föreningar till skydd eller nytta för plantan. Dessa som föreningar kan då interagera med andra växter och organismer till exempel som ett skydd mot att bli uppäten, som en lockelse för att bli uppäten så att plantan kan sprida sig vidare eller mot bakterieangrepp mm. Det som skiljer ett gift och ett läkemedel kan ibland bara vara dosen, ta till exempel flugsvampen som är giftig i hög dos men som bara ger ett hallucinogent rus vid låg dos, något vikingarna utnyttjade frekvent. Med tiden har schamanerna... (More) - Popular Abstract in Swedish
I flera tusentals år har människan använt sig av naturen till hjälp för att bota åkommor och krämpor. Det som hon har dragit nytta av då är att alla växter och plantor producerar flertalet små föreningar till skydd eller nytta för plantan. Dessa som föreningar kan då interagera med andra växter och organismer till exempel som ett skydd mot att bli uppäten, som en lockelse för att bli uppäten så att plantan kan sprida sig vidare eller mot bakterieangrepp mm. Det som skiljer ett gift och ett läkemedel kan ibland bara vara dosen, ta till exempel flugsvampen som är giftig i hög dos men som bara ger ett hallucinogent rus vid låg dos, något vikingarna utnyttjade frekvent. Med tiden har schamanerna bytts ut mot kemister i vita rockar och nu undersöker vi naturen på ett systematiskt sätt där föreningar i växter, naturprodukter, blir isolerade och analyserade för sammansättning och struktur.
Mitt bidrag till denna vetenskap är att jag har byggt några av de här föreningarna i laboratoriet på ett annat vis än vad växterna gör. Detta för att kunna testa dem mot olika sjukdomar utan att behöva skövla hela skogar för att få tillräckligt mängd. Dessutom kan man då göra små variationer av föreningarna som gör dem till naturproduktlika med förhoppningsvis förbättrade och mer selektiva egenskaper.
Jag har syntetiserat flertalet olika naturprodukter och variationer av dessa och de har eller skall testas mot allt från smärtlindring, till astma och parasiter. Vi har hittat substanser från Cannabis Sativa som ger smärtlindring utan att ge några hallucinogena effekter. Vi har undersökt kolesterol sänkande preparat, statiner för deras antiinflammatoriska effekter samt syntetiserat en del variationer av dessa för att kunna finjustera och optimera effekten. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4407344
- author
- Killander, Dan LU
- supervisor
-
- Olov Sterner LU
- opponent
-
- Docent Kann, Nina, Chalmers Tekniska Högskola
- organization
- publishing date
- 2014
- type
- Thesis
- publication status
- published
- subject
- keywords
- SAR, natural product, total synthesis, benzochromene, fluorene, cannabinoid, statin, TRPA1, TSLP, antiprotozoal, nociception, asthma, inflammation
- pages
- 180 pages
- publisher
- Department of Chemistry, Lund University
- defense location
- Chemistry center, lecture hall K:E
- defense date
- 2014-05-23 09:30:00
- ISBN
- 978-91-7422-354-5
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)
- id
- d769ced8-ea17-430b-98bf-9a1720f66266 (old id 4407344)
- date added to LUP
- 2016-04-04 11:25:56
- date last changed
- 2018-11-21 21:04:48
@phdthesis{d769ced8-ea17-430b-98bf-9a1720f66266,
abstract = {{Natural products have until recently provided the only remedy for treatment of diseases. The development of modern chemistry in the last centuries has opened the door for tapping into the chemical diversity found in nature. Synthetic natural products, together with analogues, are an important piece in the puzzle towards curing many ailments. In this thesis, synthetic endeavors towards different biological targets are presented.<br/><br>
<br/><br>
A plant derived cannabinoid was synthesized and shown to have nociceptive properties in mice, by activating the TRPA1 receptors in the spinal cord, without having any activity on the cannabinoid receptors.<br/><br>
Chronic obstructive pulmonary disease (COPD) is a growing health problem and the cytokine thymic stromal lymphopoietin (TSLP) has been shown to play a key role. By semisynthesis of TSLP inhibitors, a structure activity relationship study was performed in order to find new TSLP inhibitors, which leave the bodily defense systems intact, and help persons with asthma or COPD.<br/><br>
<br/><br>
Parasitic illnesses often lack efficient treatments, thus a total synthesis of pulchrol and pulchral, natural antiprotozoal benzochromenes, and the preparation of a library of analogues for a SAR study, is presented. Furthermore, a synthetic effort towards the total synthesis of the plant metabolite pulcaffeate is presented, a compound that also has been shown to possess antiprotozoal activity.<br/><br>
<br/><br>
By targeting different biological systems, new compounds are developed and tested, In the case of the synthesis of the bioactive benzochromenes, this led to the finding of a method for synthesizing either benzochromene or fluorene compounds from a common starting material. This could possibly be of interest for the synthetic organic chemists in the future.}},
author = {{Killander, Dan}},
isbn = {{978-91-7422-354-5}},
keywords = {{SAR; natural product; total synthesis; benzochromene; fluorene; cannabinoid; statin; TRPA1; TSLP; antiprotozoal; nociception; asthma; inflammation}},
language = {{eng}},
publisher = {{Department of Chemistry, Lund University}},
school = {{Lund University}},
title = {{Synthesis of bioactive natural products and analogues}},
year = {{2014}},
}