- Design and synthesis of a novel class of sugar-peptide hybrids: C-linked glyco β-amino acids through a stereoselective "acetate" Mannich reaction as the key strategic element
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A new type of sugar-amino acid hybrid, which is comprised of a sugar unit (gluco-, galacto-, or mannopyranose) linked through a C-glycosidic linkage to the β-position of an α-unsubstituted β-amino acid unit, is presented. It is hypothesized that these new compounds, or the oligomeric peptides derived therefrom, might possess the structural features of β-amino acid oligomers and the chemical and enzymatic resistance of C-glycosides to hydrolysis. The synthetic strategy is based on a new Mannich-type reaction between a chiral acetate enolate equivalent and α-amido sulfones derived from the corresponding sugar-C-glycoside aldehydes. While the sugar-C-glycoside aldehyde partner is prepared from well-established transformations on known sugar precursors, the lithium enolate derived from (1 R)-endo-2-acetylisoborneol 3 is employed as the key element. This Mannich approach proceeds with essentially perfect diasteromeric control leading to the new β-amino carbonyl adducts in good yields. Further, cleavage of the camphor auxiliary is smoothly performed by oxidative treatment with ammonium cerium nitrate (CAN). Complementarily, direct peptide-type coupling of the β-amino carbonyl Mannich adducts with an α- or β-amino acid residue and subsequent CAN-promoted detachment of the auxiliary yields dipeptide fragments bearing a sugar-containing aliphatic side chain and is a process that can be iterated. A preliminary conformational study based on the combination of experimental NMR data and molecular mechanics and molecular dynamics (MD) of one particular adduct is also provided.
- Palomo, Claudio,Oiarbide, Mikel,Landa, Aitor,Gonzalez-Rego, M. Concepcion,Garcia, Jesus M.,Gonzalez, Alberto,Odriozola, Jose M.,Martin-Pastor, Manuel,Linden, Anthony
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p. 8637 - 8643
(2007/10/03)
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- α-Oxymethyl ketone enolates for the asymmetric Mannich reaction. From acetylene and N-alkoxycarbonylimines to β-amino acids
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The insufficient diastereoselectivity and generality, which are the main problems of the 'acetate' aza - aldol reaction, can now be addressed through the reaction of the lithium enolate of endo-O-trimethylsilyl acetyl isoborneol with various N[(p-tolylsul
- Palomo, Claudio,Oiarbide, Mikel,Gonzalez-Rego, M. Concepcion,Sharma, Arun K.,Garcia, Jesus M.,Gonzalez, Alberto,Landa, Cristina,Linden, Anthony
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p. 1063 - 1066
(2007/10/03)
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