Solid-phase SN2 macrocyclization reactions to form beta-turn mimics.
[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.
Feng
Y
Y
Department of Chemistry, Texas A & M University, College Station 77842-3012, USA.
Pattarawarapan
M
M
Wang
Z
Z
Burgess
K
K
D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003500:Cyclization; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D012694:Serine / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D047090:beta-Lactams / Q000138:chemical synthesis*
D010455:Peptides; D011506:Proteins; D047090:beta-Lactams; D012694:Serine