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New Methods for the...
New Methods for the Synthesis of 3-Substituted 1-Indanones : A Palladium-Catalyzed Approach
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- Arefalk, Anna, 1974- (författare)
- Uppsala universitet,Institutionen för läkemedelskemi
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Hallberg, Anders (preses)
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Larhed, Mats (preses)
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- Carretero, Juan Carlos, Professor (opponent)
- Universidad Autónoma de Madrid, Madrid
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(creator_code:org_t)
- ISBN 9155463665
- Uppsala : Acta Universitatis Upsaliensis, 2005
- Engelska 66 s.
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Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 1651-6192 ; 18
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- In medicinal chemistry, there is a constant need for new preparative methods, both to make the synthesis process more effective, and to increase the accessibility to a wide variety of compounds. A number of different approaches can be used to attain these goals. Transition metal catalysis is generally performed under mild conditions, providing both regio- and chemoselective reactions. Thus, it offers an attractive means of preparation of complex drug candidates. Two additional methodologies used to increase the preparative efficiency are one-pot protocols and controlled microwave heating. One-pot and multi-component reactions are less time consuming than step-by-step reactions, and microwave heating has been used to considerably shorten the reaction times. This thesis describes a new palladium-catalyzed, one-pot reaction producing racemic acetal-protected 3-hydroxy-1-indanones from ethylene glycol vinyl ether and triflates of salicylic aldehydes. The triflates were prepared using controlled microwave heating. The reaction sequence starts with a regioselective internal Heck coupling, followed by an annulation cascade. By including secondary amines in the reaction mixture, the reaction was further developed into a three-component reaction delivering racemic acetal-protected 3-amino-1-indanones. This new method was utilized for the synthesis of primary, secondary and tertiary aminoindanones. Finally, by using enantiopure t-butyl sulfinyl imines, derived from salicylic aldehyde triflates and ethylene glycol vinyl ether as starting materials in a closely related type of palladium coupling–annulation sequence, a stereoselective protocol providing enantiomerically pure 3-amino-1-indanones was developed. To demonstrate an application in medicinal chemistry, the enantiopure 3-amino-1-indanones were incorporated as P2 and/or P2´ substituents into active HIV-1 protease inhibitors.
Ämnesord
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- Organic chemistry
- Heck
- palladium
- indanone
- annulation
- microwave heating
- triflate
- sulfinyl imine
- HIV-1 protease inhibitor
- Organisk kemi
- Organic chemistry
- Organisk kemi
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
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