S-Michael Additions to Chiral Dehydroalanines as an Entry to Glycosylated Cysteines and a Sulfa-Tn Antigen Mimic

Abstract

Stereoselective sulfa-Michael addition of appropriately protected thiocarbohydrates to chiral dehydroalanines has been developed as a key step in the synthesis of biologically important cysteine derivatives, such as S-(β-D-glucopyranosyl)-D-cysteine, which has not been synthesized to date, and S-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-cysteine, which could be considered as a mimic of Tn antigen. The corresponding diamide derivative was also synthesized and analyzed from a conformational viewpoint, and its bound state with a lectin was studied.

Chemoselective Glycosylation of Peptides through S‐Alkylation Reaction

“…As found for 4 a , NOE contacts between Glc H 1 and Cys H β /H α (see the Supporting Information) confirmed an excellent chemoselectivity for the Cys thiol over potentially competing His and Trp sites. The 1 H NMR chemical shift of the anomeric Glc H 1 was approximately 4.9 ppm (and 3 J H1,H2 =9.8 Hz) for all three compounds, indicating the β‐configuration of the glucopyranose ring . This is consistent with the expected S N 2 reaction mechanism …”

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

“…As part of our ongoing research on the use of the unsaturated amino acid dehydroalanine (Dha) in organic synthesis [26–37], we have focused our attention on the syntheses of tryptophans, cyclo-tryptophans (also known as pyrroloindolines), and tryptophan-containing natural products from simple indole starting materials [38–44]. …”

Elusive Dehydroalanine Derivatives with Enhanced Reactivity

“…In addressing this topic, we have reported the synthesis of chiral dehydroalanine (Dha) and dehydrobutyrine (Dhb) building blocks and their application in the asymmetric synthesis of lanthionine and β‐methyllanthionine derivatives . Our first‐generation chiral Dha scaffold was a versatile Michael acceptor towards nucleophilic thiols such as protected 1‐thiocarbohydrates …”