Title

Synthesis Of N-(Hydroxy)Amide- And N-(Hydroxy)Thioamide-Containing Peptides

Abstract

Methods developed with N-(benzoyloxy)amines and hydroxamic acids were used in the synthesis of N-(hydroxy)amide-containing pseudopeptides. Acylation of N-(benzoyloxy)phenethylamine with the acid chloride of N(α)- Fmoc-L-leucine provided a N(α)-Fmoc-N-(benzoyloxy)-L-leucinamide in 90% yield. Deprotection of the benzoyl group (using 10 vol % NH4OH/MeOH) provided the N(α)-Fmoc-N-(hydroxy)-L-leucinamide in 87% yield. In general, the appended Fmoc group allowed for further elaboration of the N-hydroxy-N- (alkyl)amides using classic peptide-coupling methods. A practical synthetic strategy was developed, and racemization issues were addressed using diastereomeric Val-Leu derivatives. In addition, N-(hydroxy)thioamides were generated from the corresponding N-(benzoyloxy)thioamides. N- (Benzoyloxy)thioamides were obtained in moderate yields (53-76%) from the reaction of the corresponding N-(benzoyloxy)amides with Lawesson's reagent (i.e., 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide). In summary, this new technology allows for the introduction of either N- hydroxyamide or N-(hydroxy)thioamide linkages into pseudopeptide chains without racemization.

Publication Date

3-10-2000

Publication Title

Journal of Organic Chemistry

Volume

65

Issue

5

Number of Pages

1442-1447

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1021/jo991589r

Socpus ID

0034629103 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/0034629103

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