Solid-Phase SN2 Macrocyclization Reactions To Form β-Turn Mimics
- 26 May 1999
- journal article
- letter
- Published by American Chemical Society (ACS) in Organic Letters
- Vol. 1 (1) , 121-124
- https://doi.org/10.1021/ol990597r
Abstract
[formula: see text] Efficient solid-phase SN2 macrocyclization reactions were sought to facilitate preparations of focused libraries of beta-turn mimetics. A very efficient, but undesired, cyclization reaction to give five-membered ring lactams 4 was identified in attempts to use O-nucleophiles. Subsequent studies focused exclusively on S-nucleophiles. These reactions gave the desired macrocyclization products 1 in high purities and good overall yields. Conformational analyses of illustrative macrocyclization products 1 via NMR, CD, and molecular simulations showed that they seem to sample both type I and type II beta-turn conformations in solution. CD studies indicate a curious relationship between the preferred conformation and the amino acids encapsulated in the macrocycles.Keywords
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