Studies toward the synthesis of novel MDM2 inhibitor candidates
Başlık:
Studies toward the synthesis of novel MDM2 inhibitor candidates
Yazar:
Dilek, Fikrican, author.
Yazar Ek Girişi:
Fiziksel Tanımlama:
xii, 49 leaves: charts;+ 1 computer laser optical disc.
Özet:
Protein protein interactions are valuable targets to discover novel anticancer agents. One of these is the p53-MDM2 interaction. In one of these interaction MDM2 protein inhibits p53 protein and may cause cancer. New drugs that inhibit this interaction are important for the treatment of cancer. One class of these anticancer agents are morpholinone derivative. In this study, it is aimed to synthesize new morpholinone derivatives. (R)-2-amino-2-(4-chlorophenyl)acetic acid was used as starting material for the synthesis. The first step was a trityl protection of amine with trityl chloride. Trityl protected amino acid was first reduced to N-Trt amino alcohol with LiAlH4 then oxidized to aldehyde by using Dess-Martin periodinane. The resulting aldehyde was reacted with 3-chlorophenylmagnesium bromide. This part of the synthesis was performed successfully. Then addition of methyl fumarate to this Grignard product was studied by a coupling reagents such as HATU. All attempts were failed. Then trityl group was removed by TFA and successfully coupled with methyl fumarate by using HATU. All cyclization reactions in the presence of a base like hydroxide, alkoxide or NaH to form morpholinone skeleton was failed. The cyclization reaction with the potassim carbonate in alcohol was successful and the morpholinone skeleton was formed.
Yazar Ek Girişi:
Tüzel Kişi Ek Girişi:
Tek Biçim Eser Adı:
Thesis (Master)--İzmir Institute of Technology:Chemistry.
İzmir Institute of Technology:Chemistry --Thesis (Master).
Elektronik Erişim:
Access to Electronic Versiyon.