N-Carbamoyl Derivatives and Their Nitrosation by Gaseous NOx − A New, Promising Tool in Stepwise Peptide Synthesis

Abstract

New uses of the N‐carbamoyl group in peptide synthesis − as an Nα‐protecting group in classical peptide coupling methods, and as a preactivating group for stepwise coupling by NCA formation − are presented. In the first application, the N‐carbamoyldipeptide esters C‐Val‐Gly‐OEt, C‐Leu‐Gly‐OEt, C‐Ala‐Gly‐OEt, and C‐Ala‐Phe‐OEt were obtained in good yields by treatment of the corresponding N‐carbamoylamino acids (CAA) with amino acid esters. Quantitative N‐deprotection without racemisation was then achieved in the solid through nitrosation by gaseous NOx. The extent of racemisation occurring in the coupling step is discussed. In the second application, an easy route to amino acid N‐carboxy anhydrides (NCAs) through nitrosation of CAA under the same conditions as above allowed straightforward “one‐pot” peptide stepwise coupling, as demonstrated by the formation of Leu‐Gly and Val‐Gly in good yields and enantiomeric excess. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synthesis, Crystal Structure and Hydrogen-Bonding Patterns in (RS)-1-Carbamoyl Pyrrolidine-2-Carboxylic Acid

“…Moreover, the intercepting angles between the average planes of the ureido and carboxyl group are 88.07(8)°and 83.15 (8)°for the residues A and B, respectively. These values agree with the value 79.08(9)°observed in the same angle for N-carbamoyl-L-proline, and differs from that observed in the two other N-carbamoyl derivatives of a-amino acids reported in the Cambridge structural database [30]; N-carbamoyl-L-asparagine [31] and N-carbamoyl-DL-aspartic acid [32], which have intercepting angles of 155.0(3)°and 164.2(5)°, respectively.…”

“…For example, N-carbamoyl-glycine causes sedative and anticonvulsant effects [3], N-carbamoyl-b-alanine has antidiabetic properties [4], N-carbamoyl-methionine is used in insulin analogues design [5], and N-carbamoyl-c-aminobutyric acid is a weak GABA antagonist [6]. Moreover, Ncarbamoyl-a-amino acids are useful intermediates in the synthesis of biologically active heterocyclic compounds [7] and peptides [8].…”

N-Boc Deprotection and Isolation Method for Water-Soluble Zwitterionic Compounds

“…The slurry was stirred for 2 h. The product was isolated by filtration of the slurry followed by a DCM wash to afford the desired peptide. Compounds 9 , 10 , 11 , and 12 are known compounds.…”

Ureido Functionalization through Amine-Urea Transamidation under Mild Reaction Conditions

“…The derivatives of N ε -[N′-(2-chloroethyl)carbamoyl]-L-lysine display anti-tumoral activity [ 15 ]. Additionally, antibiotic agents such as oxazolidinone can be prepared from N-carbamoylamino alcohols [ 16 ], and N-carbamoylaminoacids are useful intermediates in the peptide synthesis [ 17 ].…”

“…Traditionally, the synthesis of ureido and ureylene materials is carried out by the reaction of amino groups with isocyanates. The most popular reagent for ureido formation is KOCN [ 3 , 7 , 8 , 9 , 17 , 18 , 19 , 20 , 21 , 22 ], which displays high reactivity and is used at temperatures from 20 to 100 °C but is a toxic reagent. There has been a growing interest to find non-isocyanate routes for the synthesis of polyurethane, polyurea and ureido-functionalized materials [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”