New Method for Chloroamidation of Olefins. Application in the Synthesis of N-Glycopeptides and Anticancer Agents

Abstract

Chloroamidation of olefins using a new reagent system (COCl)2-AgNO3-CH3CN was observed. Various glycals with this reagent system produce 2-chloro-1-acetamido sugars in good yields which, in turn, were converted to free amino derivatives and various glycopeptides. The acetamido sugar derivatives and free amines were found to be promising anticancer agents against the U-87 malignant glyoma (a brain tumor) cell line with IC-50=1 nm-22 microM, and they were found to be far less cytotoxic against a normal human embryonic kidney cell line.

Efficient and Stereodivergent Syntheses of D‐ and L‐Fagomines and Their Analogues

“…[22,23] Benzyl (4S,5R,6R)-4,5-Bis(benzyloxy)-6-(benzyloxymethyl)-3-chlorotetrahydro-2H-pyran-2-ylcarbamate (9a): Benzyl chloroformate (CbzCl) (0.54 g, 3.19 mmol) and saturated aq. NaHCO 3 solution (5 mL) were added at room temperature to a mixture of chloroamine 8a (1 g, 2.13 mmol) and EtOAc (7 mL).…”

“…In continuation of our efforts directed towards the synthesis of new glycosidase inhibitors from carbohydrate derivatives, [21] here we report short and efficient syntheses of -and -fagomines and their epimers by two methodologies newly developed in our laboratory [22,23] for the preparation of 2-deoxy-1-amino sugar derivatives from -glycals.…”

Glycoside Mimics from Glycosylamines: Recent Progress

“…As miscellaneous examples, 2-deoxy glycosylamines of type 69 could be synthesized through vicinal amino chlorination of related glycals 70 [96]. …”

Direct Addition of Amides to Glycals Enabled by Solvation‐Insusceptible 2‐Haloazolium Salt Catalysis

“…[5] However,the glycosylated amide bond of the Asn side chain can be readily hydrolyzed by glycoamidases, [6] and crystallographic analysis and site-directed mutagenesis have revealed that these enzymes require the 2-acetamide group on the Asnlinked GlcNAc for substrate recognition. [10,11] The direct 2-deoxyglycosylation of nucleophiles with glycals is one of the most straightforward approaches to 2-deoxysugar compounds. Despite the utilities of the N-(2-deoxysugar)-amide structure in the fields of biochemistry and pharmacology,o nly limited synthetic methodologies for this structure have been reported.…”