883143-12-2Relevant academic research and scientific papers
Design and synthesis of glucose-templated proline-lysine chimera: polyfunctional amino acid chimera with high prolyl cis amide rotamer population
Zhang, Kaidong,Schweizer, Frank
experimental part, p. 576 - 585 (2009/05/11)
We describe the synthesis of two glucose-templated proline-lysine chimeras (GlcTProLysCs) that differ in the stereochemistry of the hydroxymethyl substituent at the C-5′ position of the pyrrolidine ring. The key synthetic steps involve C-glycosylation of an exocyclic glucose-based epoxide with allyltributylstannane, which affords functionalized C-ketosides containing an α-hydroxy ester moiety; introduction of an amino group at C-2 through stereoselective reductive amination; and regioselective installation of the azide group at C-6 on the glucose scaffold. Incorporation of these chimeras into the model peptides Ac-GlcTProLysC-NHMe and Ac-GlcTProLysC-OMe demonstrates that the stereochemistry of the hydroxymethyl substituent at the C-5′ position has a profound effect on the equilibrium constant of prolyl amide cis/trans isomerization. The equilibrium constant Kc/t for the peptide mimic Ac-GlcTProLysC-NHMe with C-5′(R) stereochemistry was determined to be 3.03 ± 0.04, while the Kt/c for the C-5′(S) diastereoisomer was 0.56 ± 0.04 in D2O. Temperature coefficient experiments indicate that the origin of these effects is derived from two critical hydrogen bonds involving the C-5′ hydroxymethyl substituent: one to the N-terminal amide carbonyl group, and the other to the primary amino group in the glucose moiety.
Synthesis of Carbohydrate-Templated Amino Acids and Methods of Using Same
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, (2008/12/08)
The present invention generally relates to tetrahydropyranyl-derivatized amino acids, their syntheses and their incorporation into peptides and peptidomimetics. The tetrahydropyran moiety constrains the side chain of an amino acid, thereby providing a molecule that may act as a sugar- or amino acid-mimetic as well as a scaffold for combinatorial synthesis.
Synthesis of sugar-lysine chimera with integrated gluco-configured 1,3-hydroxyamine motif
Zhang, Kaidong,Wang, Jialiang,Sun, Zhizhi,Nguyen, Dung-Huang,Schweizer, Frank
, p. 239 - 242 (2007/10/03)
The paper describes the synthesis of glucose-configured sugar-lysine chimeras in which the side chain of lysine is conformationally constrained via incorporation into a D-glucose scaffold. Key step in the synthesis is a high-yielding, reductive ring opening of an exocyclic glucose-derived epoxide to form an α-hydroxyester that can be converted into chimeric sugar-lysine analogues. To demonstrate the use of these novel chimeric sugar-lysine building blocks in peptide coupling, we replaced D-lysine in the antimicrobial dipeptide sequence kW by a D-glucose-D-lysine chimera. Georg Thieme Verlag Stuttgart.
Synthesis of spirocyclic glucose-proline hybrids (GlcProHs)
Zhang, Kaidong,Schweizer, Frank
, p. 3111 - 3115 (2007/10/03)
A short synthetic route to polyhydroxylated spirocyclic glucose-based L-proline analogues is described from easily prepared 2,3,4,6 tetra-O-benzyl-D-glucono-lactone. The synthesis involves C-glycosylation of an exocyclic glucose-based epoxide with allyltributylstannane that affords functionalized C-ketosides containing an α-hydroxy ester moiety. Oxidation of the alcohol function, followed by stereoselective reductive amination provides an amine that undergoes iodine-induced aminocyclization to provide spirocyclic glucose-proline hybrids bearing an iodomethylene side-chain. The iodo function of the side-chain can be converted into other functional groups such as ester and hydroxyl groups, thereby allowing additional modifications to the pyrrolidine ring. Georg Thieme Verlag Stuttgart.
