Macrocyclic peptides, 4. Preparations and enantioface‐differentiating abilities of 27‐ and 36‐membered ring peptides containing N,N′‐ethylene‐bridged dipeptides and glycine

Abstract

27-and 36-membered ring peptides were prepared using glycine, (2S, 3'S)4methyL2-(2'-oxo-3'-isobutyl-l '-piperaziny1)pentanoic acid (2) and (2 S,3' S)-3-pheny1-2-(2'-0~0-3'-benzyl-l '-pipera-ziny1)propanoic acid as the units of peptides. The interactions of 1-phenylethylammonium (1) and p-methoxy-I-phenylethylammonium bromides (11) with these cyclic peptides were studied by 'H and 13C NMR measurements in CDCI,. It was found from these results that the peptides distinguish the enantiomers (Rand S-isomers) of the substrates. Furthermore, it was shown that the enantioface-differentiating abilities of 36-membered ring peptides are superior to those of , 27-membered rings. 0 1990, HUthig & Wepf Verlag, Basel CCC 0025-1 16X/90/$03.00

Conformations of 24-Membered Ring Pseudopeptides Containing N,N′-Ethylene-Bridged Dipeptides Constructed from (S)-Alanine, -Leucine, -Isoleucine, and -Phenylalanine

“…The macrocyclic peptide concentrations in 1 H and 13 C NMR measurements were 0.075 and 0.040moldm-3 , respectively, in DMSO-d 6 .…”

“…13 C Spin-lattice relaxation times (T1) were measured at 40°C using a 180°-r-90°-AQ pulse sequence. Interval between pulse sequences was 10s.…”

New fMLF-OMe Analogues Containing Constrained Mimics of Phenylalanine Residue

“…The cyclization and esterification of (2S,7S)-2,7-dibenzyl-3,6-diazaoctane-1,8-dioic acid (N,N′-ethylene-bridged bis-(S)-phenylalanine, HO-PheePhe-OH) (5) [25,26] in boiling methanol, using p-toluenesulphonic acid monohydrate (Tos-OH . H2O) as an acid catalyst [27,28] , afforded methyl (2S,3′S)-2-(3′-benzyl-2′-oxopiperazin-1′-yl)-3-phenylpropanoate (ePhePhe-OMe) (6) [27,28] .…”

“…Following known procedures [27,28] , HO-PheePhe-OH (5) [25,26] (0.178 g, 0.5 mmol) was refluxed with Tos-OH . H2O (0.19 g, 1 mmol) in dry methanol (7.5 ml) for 24 h. The salt obtained after evaporation of the solvent was freed by saturated aqueous NaHCO3, cooling at 0 °C, and the mixture was extracted with dichloromethane.…”

A Cyclic Hexa-Pseudopeptide Constructed from N,N'-Ethylene-Bridged (S)-Phenylalanyl-(S)-Phenylalanine and Glycine

“…It has been shown by us that modification of the macrocyclic skeleton using N,N'-ethylene bridges can provide fixed and deep cavities without the formation of intramolecular hydrogen bonds (Kojima, Yamashita & Miyake, 1995). This paper describes the crystal structure of a new 18-membered cyclic pseudopeptide, cyclo-(Gly-eFF)2 [where Gly is glycine and eFF is (2S, YS)-2-(3'-benzyl-2 ~-oxopiperazin-l'-yl)-3-phenylpropanoic acid] (Yamashita et al, 1990).The two piperazin-2-one rings are approximately perpendicular to the 18-membered ring, forming a deep cavity in the center of this macrocyclic pseudopeptide (Fig. 1).…”