MW-​enhanced high-​speed deprotection of Boc group using p-​TsOH and concomitant formation of N-​Me-​amino acid benzyl ester p-​TsOH salts

A high-​speed, complete deprotection of Boc group from Boc (Boc = tert-​butoxycarbonyl) amino acids and protected peptide esters employing p-​TsOH in toluene under microwave irradn. is found to be complete in 30 s. The deprotection can be carried out in methanol and acetonitrile also. Under the present conditions, C-​peptide benzyl esters and O-​benzyl ethers have been found to be stable. This has permitted us to carry out the synthesis of [Leu]​enkephalin employing the Boc​/Bzl-​group strategy. Further more, it has been found that both Nα-​Fmoc (Fmoc = 9-​fluorenylmethyloxycarbonyl) and Nα-​Z (Z = benzyloxycarbonyl) groups are completely stable. The present conditions can be extended for the concomitant removal of the Boc group and the formation of C-​benzyl amino acid esters as well. This has been utilized for the synthesis of N-​Me amino acid benzyl esters starting from Boc-​N-​Me amino acids in a single step

Synthesis of peptidyl ureas using p-​nitrophenyl (9-​fluorenylmethoxycarbonylamino)​methylcarbamate derivatives

Carbamates Fmoc-​NHCHRNHCO2C6H4NO2-​p (Fmoc is 9-​fluorenylmethoxycarbonyl, R is an amino acid side chain) were prepd. using isocyanates derived from Fmoc-​amino acid azides and p-​nitrophenol in the presence of an equimolar quantity of N-​ethyldiisopropylamine. The carbamates were coupled with amino acid ester hydrochlorides to afford dipeptidyl ureas

Homologation of <i>α</i>-amino acids to <i>β</i>-amino acids: 9-Fluorenylmethyl chloroformate as a carboxyl group activating agent for the synthesis of <i>N^α-</i> protected aminoacyldiazomethanes

2152-2158An efficient and stereospecific homologation of urethane-protected α-amino acids to β-amino acids by Arndt-Eistert approach using an equimolar mixture of Fmoc-/Boc-/Z-α-amino acid and 9-fluorenylmethyl chloroformate for the acylation of diazomethane synthesizing the key intermediates Fmoc-/Boc-/Z-α-aminoacyldiazo-methanes as crystalline solids is described. They are then converted to the corresponding,β-amino acids using silver benzoate/1,4-dioxane-water under microwave irradiation. All the protected β-amino acids prepared have been obtained in good yield as well as purity

2,4,5-Trichlorophenyl-(9<i>H</i>-fluoren-9-ylmethoxycarbonylamino)methylcarbamates: Synthesis, isolation, characterization and utility in the synthesis of dipeptidyl ureas

1046-1053An efficient synthesis of 2,4,5-trichlorophenyl-(9H-fluoren-9-ylmethoxycarbonylamino)methylcarbamates employing isocyanates derived from several Fmoc-amino acids has been described. All the carbamates made have been obtained as crystalline solids and are fully characterized by IR, 1H NMR, 13C NMR and mass spectrometry. They have been used as building blocks for the synthesis of several dipeptidyl urea esters. The coupling of carbamates with N,O-bis[trimethyl­silyl]amino acids resulted in Fmoc-protected dipeptide urea acids in good yield as well as purity. All the dipeptidyl urea esters and acids made have been well characterized