Trans- -ACPC

The reduction produces a mixture of four diasteomers in which a trans- (ACPC derivatives) or a cis- isomer (ACHC derivatives) is the major product. In the former case, treatment of the mixture with 4 N HCl in dioxane led to the precipitation of the trans isomer hydrochloride salt. One recrystallization from acetonitrile enriched the optical purity to >99% de [120, 122] In the latter case, epimerization... 

Fig. 2.40 Sequences and helical wheel representation of amphiphilic 2.5,2-helical jS-pep-tide 17-mers evaluated for antimicrobial activity [234, 248]. These peptides are exclusively composed of hydrophobic trans-ACPC...

As predicted computationally, the trans-ACPC oligomers revealed a different type of helical conformation in both solution and the solid state. Crystal structures of the trans-ACPC hexamer and octamer displayed the 12-helical conformation (Figure 29).238 241 The spectral data of the ACPC oligomers in solution are consistent with the crystallographic observations. 

Figure 29. Side and top views of ca. one turn of the 12-helix extracted from the crystal structure of Gellman s trans-ACPC hexamer.241 A single S(12) H bond circuit in the peptide backbone has been rendered as thick cylinders. Additionally, a residue has been rendered as a space filling model to provide a frame of reference between the two views and to more clearly show the spatial relationship between cyclopentyl groups.

Trans-ACPC with (15,25) configuration was prepared in an elegantly short pathway (Scheme 13) by Enders et al. By addition of the chiral ammonia equivalent lithiated (5)-(-)-2-methoxymethyl-1 -trimethylsilylaminopyrro-lidine (TMS-SAMP) to co-halide-substituted enoate 84, followed by Michael-initiated ring closure (MIRC), 85 was formed with 96-98% diastereoselectivity (Scheme 13). After desilylation,... 

Macro-azo-initiators containing crown ether units were successfully synthesized by Yagci et al. [37,38] condensing ACPC with the c s or trans forms of 4,4 -diaminodibenzo-18-crown-6 (Scheme 8). The polymeric... 

Physicochemical data such as dielectric increments [35], partial molar volumes [36] and protonation and complex formation constants [37, 38], were earlier determined for racemic cis- and trans-2-ACPC. 

The enantiomers of trans-2-ACPC were separated by Yamazaki et al. [78]. The Boc-protected racemic amino acid was acylated with / -(+)- -methylbenzylamine by use of a mixed anhydride (Scheme 5). The diastereomers 34 and 35 were separated by silica gel column chromatography after removal of the acid-labile Boc group. The absolute configuration was proved by X-ray diffraction of 35. The amino acid enantiomers 36 and 37 were obtained after strong acid treatment of 34 and 35, and anion-exchange desalting of the product [78]. 

Kanerva et al. resolved ethyl esters of ten alicyclic (i-aminocarboxylic acids by lipase catalysis in organic solvents. The resolutions were based on acylation of the amino group at the / -stereogenic centre with various 2,2,2-trifluoroethyl esters. From the cis and trans racemic esters 42, all four enantiomers of 2-ACPC were prepared. The absolute configurations of 43 and 44 were proved by transformation to the known 2-ACPC enantiomers by hydrolysis and subsequent desalting with an anion-exchange resin [85]. 

A number of simple transformations of cis- and trans-2-ACPC have been carried out, under practically the same conditions as for a-amino acids. 

A number of tetrapeptide analogues related to morphiceptin were synthetized in which the proline in the second position was replaced with cis- or trans-2-ACPC [41, 169, 170]. The synthetic scheme is shown in Figure 1. The diastereomers were separated by using preparative HPLC. By means of this pathway, the following peptides were prepared Tyr-(lR,2iS)-ACPC-Phe-Val-NH2, Tyr-(lS,2R)-ACPC-Phe-Val-NH2, Tyr-(l/ ,2iS)-ACPC-Phe-D-Val-NH2, Tyr-(lS,2R)-ACPC-Phe-D-Val-NH2, Tyr-( 1 R,25)-ACPC-Phe-Pro-NH2, Tyr-(lS,2R)-ACPC-Phe-Pro-NH2 and... 

H NMR data [171, 173]. The following sequences were prepared c[( 15,25)-ACPC-Phe-D-Trp-Lys-Thr-Phe], c[(l/ ,2/ )-ACPC-Phe-D-Trp-Lys-Thr-Phe], c[(l/ ,25)-ACPC-Phe-D-Trp-Lys-Thr-Phe] and c[(15,2/ )-ACPC-Phe- )-Trp-Lys-Thr-Phe]. The synthetized analogues contain a trans amide bond in the bridging region, which leads to the loss of binding activity [173]. 

Various 7-aminobutyric acid (GABA) analogues, among them cis- and trans-2-AC C, were investigated as potential inhibitors of the GABA uptake in brain synaptosomes and in synaptic membrane vesicles [180-182]. cis-2-ACPC was found to be a potent inhibitor of the GABA uptake in the synaptosomes. The trans counterpart proved to be half as potent as the cis isomer [182]. 

Adlington et al. (338) first prepared cis- and trmis-[2,3- H2]-ACPC [340 + 341] and [343 + 344] from trans- and cis-[l, 2- H2]-ethylenes via meso-and d/-[l, 2- H2]-1,2-dibromoethanes 338 and 342, respectively (Scheme 86). Reaction of these with the lithium salt 339 then gave the desired products. The stereochemistry was confirmed using computer-simulated HNMR spectral comparison. The cis-isomer has also been prepared by Pirrung (339) using the meso-dibromide 338 in a method worked out by Schollkopf. These methods have been used by Ramalingam et al. (340), who also used a similar technique to prepare [2,2- H2]-ACPC. 

In contrast, oligopeptides of frani -2-amino-cyclopentane-carboxylic acid (fran -ACPC) formed a 12-helix, both in solution and in the solid state. The orientation of amide residues with respect to the helix N-terminus to C-terminus polarity is opposite in trans-ACRC and frans-ACPC... 

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