Design and synthesis of novel oxetane β3-amino acids and α, β-peptides

• Published in: Tetrahedron 2015-04, Vol.71 (14), p.2158-2167
• Main Authors: Sharma, Gangavaram V.M., Venkateshwarlu, Gajulapati, Katukuri, Sirisha, Ramakrishna, Kallaganti V.S., Sarma, Akella V.S.
• Format: Article
• Language: English
• Subjects: Mosher amides; Oxetane side chain; Oxetane β3-amino acid (β3-Oaa); α, β-Peptides; β-Amino acids
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2015.02.039

The study describes synthesis of (S)- and (R)-oxetane-β3-amino acid (β3-Oaa) monomers from diacetone glucose (DAG). The oxetane ring is prepared by a nucleophilic cyclization reaction, wherein, the C-3 and C-4 stereocenters of DAG represent the C-2 and C-1 of oxetane ring, respectively. The hydroxy methyl group generated from C-1/C-2 was used for the ring formation, and C-5/C-6 of DAG were used for the introduction of amine and ester groups via aza-Michael addition reaction on the α, β-unsaturated ester. The stereochemistry at the newly created amine center was defined through modified Mosher method. The (S)-β3-Oaa monomer and l-Ala were used for the synthesis of regular 1:1 was converted into α, β-peptides. The conformational analysis of the peptides revealed the presence of 11/9-helical patterns from the NMR, CD and MD studies. [Display omitted]