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.

journal_name

Amino Acids

journal_title

Amino acids

authors

De Marco R,Cavina L,Greco A,Gentilucci L

doi

10.1007/s00726-014-1839-3

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

2823-39

issue

12

eissn

0939-4451

issn

1438-2199

journal_volume

46

pub_type

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