Dedicated to Prof. Elias J. Corey on the occasion of his 80th birthday Cyclo-b-tetrapeptides are known to adopt a conformation with an intramolecular transannular hydrogen bond in solution. Analysis of this structure reveals that incorporation of a b 2 -amino-acid residue should lead to mimics of a-peptidic b-turns (cf. A, B, C). It is also known that short-chain mixed b/a-peptides with appropriate side chains can be used to mimic interactions between a-peptidic hairpin turns and G protein-coupled receptors. Based on these facts, we have now prepared a number of cyclic and open-chain tetrapeptides, 7 -20, consisting of a-, b 2 -, and b 3 -amino-acid residues, which bear the side chains of Trp and Lys, and possess backbone configurations such that they should be capable of mimicking somatostatin in its affinity for the human SRIF receptors (hsst 1-5 ). All peptides were prepared by solid-phase coupling by the Fmoc strategy. For the cyclic peptides, the three-dimensional orthogonal methodology (Scheme 3) was employed with best success. The new compounds were characterized by high-resolution mass spectrometry, NMR and CD spectroscopy, and, in five cases, by a full NMRsolution-structure determination (in MeOH or H 2 O; Fig. 4). The affinities of the new compounds for the Fig. 1. Molecular formulae of somatostatin (SRIF-14) and Sandostatin , and X-ray crystal structure of Sandostatin [11] 16 ) One of the first to recognize the quasi-high-dilution effect with polymer-bound reagents and intermediates was Patchornik [39]. 17 ) Cf. the use of a simple thioester linkage [45]. 18 ) For some representative examples, see [31] [46]. 19 ) Besides the somatostatin-mimicking cyclopeptides described herein, we have also synthesized RGD-mimicking cyclopeptides, and, in all cases, the yields obtained with the safety catch method were disappointingly low. Scheme 2. Cyclopeptide Head-to-Tail Synthesis by the Kenner -Ellman Safety Catch Methodology [43].The 4-sulfamoyl-butyryl AM resin is commercially available. For activation of the acyl-sulfonamide group, the sulfamoyl N-atom is alkylated (R' ¼ Me, CH 2 CN). In the cyclization step, the peptide is removed from the resin, with the side-chain functional-group protection still in place [44]. This method was applied to the synthesis of the cyclo-b-tetrapeptide 7.Helvetica Chimica Acta -Vol. 91 (2008) 20 ) In the spectrum of 18, this second Cotton effect is at 220 nm! Fig. 2. Normalized CD spectra of cyclic tetrapeptides 10 -14 recorded in MeOH (0.2 mm). The CD spectra of compounds 7 -9 have not been recorded. Fig. 4. NMR Solution structures of the cyclic tetrapeptides 7, 9, and 14 , and of the open-chain tetrapeptides 16 and 17. Low-energy structures derived from SA annealing calculations are shown.

The synthesis of substituted imidazolo[1,2‐a]‐L‐arabino‐piperidinoses is reported. The substituents are methyl, phenylmethyl, phenylethyl, cyclohexylethyl, pyridinylethyl, piperidinylethyl, phenylpropyl and hydroxymethyl. All substituents are connected to the imidazole moiety. Examination of the inhibitory properties of the newly synthesised compounds against a β‐glucosidase (from almonds) and a β‐galactosidase (from Escherichia coli) lead to the conclusion that the substitution of the C‐2 position on the imidazole moiety with cyclohexylethyl or phenylethyl gives the best results (Ki = 2 and 4 nM, respectively, against a β‐galactosidase) as compared with the non‐substituted azasugar. The synthesis of the imidazolo[1,2‐a]‐D‐xylo‐piperidinose substituted with phenylethyl is also reported, as well as its inhibitory potency against the β‐xylosidase from Aspergillus niger.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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