title: Easy preparation of dehydroalanine building blocks equipped with oxazolidin-2-one chiral auxiliaries, and applications to the stereoselective synthesis of substituted tryptophans.
abstract: Chiral dehydroamino acid building blocks are versatile starting materials for the preparation of optically active unusual amino acids and other compounds of pharmacological interest. Herein we disclose the expedient preparation of dehydroalanines (ΔAla) equipped with oxazolidin-2-one (Oxd) chiral auxiliaries, Ts-Oxd-ΔAla-OMe. These compounds have been obtained in high yields from dipeptides Ts-Ser/Thr/phenylSer-Ser-OMe by the one-pot cyclization-elimination reaction with N,N-disuccinimidyl carbonate and catalytic DIPEA. To test the efficacy of the chiral auxiliaries in controlling asymmetric transformations, the Friedel-Crafts alkylations of indoles carrying diverse substituents were performed in the presence of Lewis and Brønsted acids. The reactions proceeded with good to excellent diastereomeric ratios giving (S)- or (R)-tryptophan derivatives, isolated very conveniently by simple flash chromatography. To verify the utility of this approach, optically pure (S)-2-methyltryptophan and (S)-5-fluorotryptophan were obtained and utilized to prepare analogues of endogenous opioid peptide endomorphin-1, H-Tyr-Pro-Trp-PheNH2.
authors.affiliation: Department of Chemistry, G. Ciamician University of Bologna, via Selmi 2, 40126, Bologna, Italy, rossella.demarco2@unibo.it.
authors.forename: Rossella
authors.initials: R
authors.lastname: De Marco
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cavina
authors.forename: Arianna
authors.initials: A
authors.lastname: Greco
authors.forename: Luca
authors.initials: L
authors.lastname: Gentilucci
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D023303:Oxazolidinones / Q000737:chemistry*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000737:chemistry; D013237:Stereoisomerism; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D023303:Oxazolidinones; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D014364:Tryptophan; C015102:dehydroalanine; D000409:Alanine