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- Berts, Wei
(author)
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Syntheses of functionalized Phe-Gly dipeptidomimetics
- 1999
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Doctoral thesis (other academic/artistic)abstract
- The complete series of Boc-protected C-4 mono- and difluoroallyl Phe-Gly dipeptidomimetics and their corresponding saturated derivatives has been synthesized. A mechanism that rationalizes the formation of the two isomeric allylic mono-fluorides from an allylic alcohol with diethylaminosulfur trifluoride (DAST) has been investigated. Most likely, the reaction proceeds via an aziridine intermediate. An allylic ketone isostere wasused as starting material for all the fluorination transformations. Two synthetic approaches to this ketone were developed.A series of vicinal diamines was synthesized by reactions of allylic cis- and transaziridines with nucleophilic amines. The nucleophiles reacted either via ring opening or 1,4-addition reactions with the α,β-unsaturated aziridines. The 1,4-addition reaction was found to be favoured in most cases. To improve the yield of ring opening products, various reaction conditions were examined. The Lewis acids Yb(OTf)3 and Zn(OTf)2 were chosen as the reaction catalysts since they are believed to coordinate differently to acylaziridines. It was observed that addition of these Lewis acids did not influence the outcome of the reaction.Five Boc-protected Phe-Gly and Phe-Phe vinyl isosteres were synthesized using a Julia olefination reaction. The epoxidation of the vinyl isosteres were performed with three different peracids and VO(acac)2/TBHP. The stereoselectivities observed in the peracid epoxidation may emanate from a cooperative coordination of the incoming peracid by the allylic carbamate group and more weakly coordinating allylic methyl ester, alcohol,and acetate functions. The vanadium catalyzed reactions demonstrated that the face selectivity in the epoxidation of the double bond of the Phe-Gly and Phe-Phe vinyl isosteres is only dependent of the steric interference.
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