Peptidosulfonamides

In this chapter we consider Fmoc solid-phase synthesis of peptide analogs containing the amide surrogate that tend to be isosteric with the natural amide. This includes synthesis of peptidosulfonamides, phosphonopeptides, oligoureas, depsides, depsipeptides, and peptoids. 

Key Words Peptidomimetics pseudopeptides isosteres Fmoc solid-phase synthesis peptidosulfonamides phosphonopeptides oligourea depsides depsipeptides peptoids. 

Fig. 3. Solid-phase peptidosulfonamide synthesis using sulfonyl chloride methodology.

To the solution containing cleaved peptidosulfonamide, add cold diethyl ether and collect the resulting precipitate by filtration. 

Liskamp, R. M. J., and Kruijtzer A. W. (2004) Peptide transformastion leading to pep tide-pep tidosulfonamide hybrids and oligo peptidosulfonamides. Mol. Divers.,... 

De Jong, R., Rijkers, D. T. S., and Liskamp, R. M. J. (2002) Automated solid-phase synthesis and structural investigation of /3-peptidosulfonamides and /3-peptidosulfonamide//J-peptide hybrids /J-peptidosulfonamide and /3-peptide foldamers are two of a different kind. Helv. Chim. Acta 85,4230 1243. 

Moree, W. J., Vand der Marel, G. A., and Liskamp R. M. J. (1995) Synthesis of peptidosulfinamides and peptidosulfonamides peptidomimetics containing the sulfinamide or sulfonamide transition-state isostere../. Org. Chem. 60, 5157-5169. 

Humljan, J., Kotnik, M., Boniface, A., et al. (2006) A new approach towards peptidosulfonamides synthesis of potential inhibitors of bacterial peptidoglycan biosynthesis enzymedMurD andMurE. Tetrahedron 62,10980-10899. 

Synthesis of model cyclic peptidosulfonamides containing 1,2,7-thiadiazonine moiety was performed by the incorporation of an amino acid on the 7-position leading to 71 (Scheme 9) <2004JOC3662>. 

Using the solid-phase strategy also libraries of other biopolymer mimetics have become accessible, for example, oligoureas, oligo-sulfones, peptidosulfonamides, [14] peptido-phosphoramidates, and peptoids (Scheme 2). 

Liskamp has reported the synthesis and the screening in asymmetric catalysis of a library of polymer-supported peptidosulfonamide [147]. Rt) or (5 -pyrrolydines 222 prepared in six steps from D or Z-tartaric acid were anchored onto Argonaut resin (0.41 mmol/g) to afford the corresponding supported pyrrolidines 223 (Scheme 91). The polymeric peptidosulfonamides 224 and 225 were then synthesized in four steps from the immobilized pyrrolidines 223. The different chiral polymers were tested in the titanium-mediated diethylzinc addition to benzaldehyde,/ -chlorobenzaldehyde, cyclohexanecarboxaldehyde and phenylacetaldehyde. Both yield and ee were very low with all these supported-ligands for the enantioselective reaction with the two aliphatic aldehydes. With aromatic aldehydes, the best results were observed with both leucine-derived supported peptidosulfonamides 224d and 225d. 

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