Dipeptide mimetics

In an approach toward dipeptide mimetics, Laufersweiler condensed ethyl pyroglutamate 255 with a range of substituted aminopyrroles 254 to generate the tricyclic system 256 in good yield (Equation 69) <2005BML4322>. 

Dipolar cycloadditions of 2-tert-butoxycarbonyl-1 -pyrroline A -oxide (627) with several chiral acrylamides (634a-f) (Scheme 2.276) followed by hydrogenolysis of cycloadducts (635) and (636) has been used in the synthesis of enantiopure tert-butyl (2RJ R)- and (2.S. 7a.S )-2-hydroxy-3-oxo-tetrahydro-l II -pyrrolizine-7a(5// )-carboxylates, useful intermediates for the synthesis of Gly-(s-cis)Pro dipeptide mimetic (790). 

Capping Croups as Amino Acid Analogues and Dipeptide Mimetics... 

JA Robl, DS Karanewsky, MM Asaad. Synthesis of benzo-fused, 7,5- and 7,6-fused azapinones as conformationally restricted dipeptide mimetics. (N-methyhnorpholine and Pht-Asp(OBzl)-Cl) Tetrahedron Lett 36, 1593, 1995. 

P. Gillespie, J. Cicariello, G.L. Olson, Conformational analysis of dipeptide mimetics. Biopolymers 43 (1997) 191-217. 

A. Otaka, F. Katagiri, T. Kinoshita, Y. Odagaki, S. Oishi, H. Tamamura, N. Hamanaka, N. Fujii, Regio- and stereoselective synthesis of ( )-Alkene frans-Xaa-Pro dipeptide mimetics utilizing organocopper-mediated Anti-S M2 reactions, J. Org. Chem. 

Y. Sasaki, A. Niida, T. Tsuji, A. Shigenaga, N. Fujii, A. Otaka, Stereoselective synthesis of (Z)-alkene-containing proline dipeptide mimetics, J. Org. Chem. 71 (2006) 4969 979. 

S. Oishi, K. Miyamoto, A. Niida, M. Yamamoto, K. Ajito, H. Tamamura, A. Otaka, Y. Kuroda, A. Asai, N. Fujii, Application of tri- and tetrasubstituted alkene dipeptide mimetics to conformational studies of cyclic ROD peptides. Tetrahedron 62 (2006) 1416-1424. 

Cheng, S. Tarby, C. M. Comer, D. D. Williams, J. P. Caporale, L. H. Myers, P. L. Boger, D. L. A Solution-Phase Strategy for the Synthesis of Chemical Libraries Containing Small Organic Molecules A Universal and Dipeptide Mimetic Template, Bioorg. Med. Chem. 1996, 4, 727. 

Vinylogous sulfonamide peptides may be considered as pseudopeptides, dipeptide mimetics, or pseudopeptides with five atoms in the backbone, instead of the usual six atoms in pro-teinogenic dipeptides (Scheme 31). 

In connection with an interest in generating /i-turn dipeptide mimetics, Piscopio and co-workers developed a solid-phase approach to the Freidinger lactam 86 via a solid-phase Ugi condensation and ring-closing metathesis (RCM) methodology [72], The resin-bound amine 85 is the equivalent of a traceless linker and the two-step protocol proceeds in good yield (Scheme 11.17). 

Robl JA, Sun C-Q et al (1997) Dual metalloprotease inhibitors mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral endopeptidase. J Med Chem 40 1570-1577... 

JA Robl, C Sun, J Stevenson, DE Ryono, LM Simpkins, MAP Cimarusti, T Dejneka, WA Slusarchyk, S Chao, L Stratton, RN Misra, MS Bednarz, MM Asaad, HS Cheung, BE Aboa-Offei, PL Smith, PD Mathers, M Fox, TR Schaeffer, AA Seymour, NC Trippodo. Dual metalloprotease inhibitors mercaptoacetyl-based fused heterocyclic dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral endopeptidase. J Med Chem 40 1570-1577, 1997. 

Cheng S, Tarby CM, Comer DD, Williams JP, Caporale LH, Myers PL, Boger DL, A solution-phase strategy for the synthesis of chemical libraries containing small organic molecules A universal and dipeptide mimetics template, Bioorg. Med. Chem., 4 727-737, 1996. 

Gouin and Murphy have reported [47] the s)uithesis of the more hydrophilic dipeptide mimetic 76 (O Fig. 9) in 13 steps from 1-DMJ [70]. This DMJ derivative lacks the benzyl group in the side chain to mimic Phe, yet still displayed a K value of 26 pM in an unspecific SST receptor assay, and it showed preferential binding to hSSTR4 (48% at 1 pM) over hSSTR5. 

Conformationally Constrained Analogs. Dermorphin analogs containing a local constraint were prepared by incorporation of a dipeptide mimetic in place of Phe -Gly". The Aba -Gly" (see Fig. 7.43) analog of dermorphin retains high affinity at [x receptors and potency in the GPI, whereas this structural modification increases S-receptor affinity and potency in the MVD 17- to 25-fold (892). A number of heterocycles are also tolerated as bond replacements for the Phe -Gly" peptide bond (893). 

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