Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The efficacy of new inductors from camphor derivatives

12.07.2005


Ainara Lecumberri Munárriz recently defended her PhD thesis at the Public University of Navarre, in which the applicability of new inductors derived from camphor in asymmetric alkylation and Diels-Alder reactions was studied.



Spatially selective synthesis

Assymetric synthesis is the process by which the molecule is made to react solely on one side. This is of interest because carbons are tetrahedral and the properties of the molecules depend on how their atoms are situated in space. In order to understand the importance of this process, we can look to the thalidomide drug of the 1970s, which was given to pregnant women to allay vomiting. The medicine had a spatial formation which, while stopping vomiting, caused malformations in the fetus, and the result was children born without hands, or arms or legs. It was as a result of this that the synthesis f molecules with a specific spatial situation was seen to be significant and, since then, great importance has been attached to stereoselective or ‘spatially selective’ synthesis.


In the Phd entitled, “The use of a´-hydroxyketones derived from camphor in asymmetric alkylation and Diels-Alder reactions”, it was proposed to optimise the conditions for producing this type of asymmetric reactions, based on camphor derivatives. After attempting different types of reactions, the ones chosen for investigation were the alkylation and Diels-Alder reactions, used for the synthesis of organic molecules, i.e. to form carbon links. In concrete, the alkylation ones to introduce substituents - alkyl or carbonated chains -, and the Diels-Alder reactions to form more complex molecules.

Her research confirmed the viability of the alkylation reactions carried out with ketones derived from camphor. Thus, using acetylene and alkyl halides, easily accesible and cheap products provide a wide variety of optically active alpha-substituted carbonylic compounds, incorporating all the carbon atoms of the substrates of the initial batch, which gives a sequence with a significant economy of atoms, i.e. a number of traditional steps in obtaining the end product are avoided. Thus, we undertook the first asymmetric variant of the classical method for transforming acetylene into alpha-substituted carboxyl compounds in a chemo-, regio- and stereoselective manner.

Also determined, for the first time, was a procedure for the asymmetric alpha-chiral hydroxyketone Diels-Alder reaction obtained from the(R)-(+)-camphor and methoxyalene, using Brönsted acids as catalysts. To date metallic catalysts have been used – derivatives of titanium, aluminium, copper, etc. Nevertheless, given that the absence of metal traces is evermore important in medication, effective organic actalysts are of great interest. Thus, in the PhD thesis it was demonstrated that, based on the corresponding cycloaducts, high-purity enantiomeric acids and ketones can be accessed easily and, moreover, the Chiral information source is recovered.

Alzheimer therapeutic agent

Over the past three decades alkylation in the alpha position of carbonylic compounds has been one of the most popular ways of forming carbon-carbon links in a regio- and stereoselective manner. The use, as Chiral auxiliaries, of oxazolidinones developed by Evans has laid down the guidelines in this field for more than a decade. Amongst the camphor derivatives used in asymmetric alkylation, special attention has been given to the Oppolzer N-acyl sultames.

Aminoalcohol derivatives have also been used. However, asymmetric alkylation based on the employment of ketone enolates has been considerably less developed, above all due to problems of regioselectivity and polyalkylation. Ketones,which have been used in aldolic and Mannich reactions, are both easily accesible from commercial products and also the alkylation aducts are transformed easily to carboxylic acids, aldehydes or alkylated ketones, and enable the recovery of the Chiral source of information.

In this way, first, preparation of the camphor-derived a-hydroxymethylketone was carried out by means of a sequence of two reactions that involve the addition of lithium acetylide to camphor and the subsequent hydratation of the triple link. Once the a´-trimethylsiloxyketones were prepared, we decided to carry out a study of the reaction of their corresponding enolates with methyl iodide as the electrophile. In every case just one isomer was obtained with yields of between 78 and 85%.

The end target was to enantiomerically synthesise pure carbonylic a-substituted compounds with recovery of the Chiral source of information. Obtaining a-substituted acids was achieved using oxidant excision with cerium nitrate and ammonia at 0ºC for an hour, obtaining acids with yields of about 90%. With the same treatment and in a simple manner, the initial batch of camphor was obtained from the organic phase with yields of between 85% and 90%, thus recovering the Chiral source of information, one of the other aims put forward. It should be emphasised that, by a simple change in the alkylation sequence, we can access one or other of the isomers.

The method described above for the alkylation of a´-hydroxyketonts derived from (R)-(+)-camphor is efficient both for reactive halides as well as for less reactive ones. Thus, it was decided to apply the same to obtaining (R)-2-propyloctanoic acid, a therapeutic agent for the treatment of Alzheimer and its enantiomere, the (S)-2-propyloctanoic acid, obtaining both with a global yield in the region of 50 % and with optical purities greater than 98%.

Irati Kortabitarte | alfa
Further information:
http://www.basqueresearch.com

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>