N-Benzyloxycarbonyl-glycine

Dibenzyl dicarbonate offers some advantages in the preparation of N-benzyloxycarbonyl amino-acids, compared to the widely used benzyl chloroformate. For example, preparation of dipeptide-free N-benzyloxycarbonyl glycine is easily achieved under standard pH-stat conditions if the pH is carefully regulated. 

N-(Benzyloxycarbonyl)glycine 576 Benzyl chloroformate (17 g) and 4N-sodium hydroxide solution (25 ml) are added separately but simultaneously, slowly and with stirring, within 20-25 min to an ice-cooled solution of glycine (7.5 g) in 2N-sodium hydroxide solution (50 ml). The mixture is then stirred for a further 10 min, whereafter it is extracted with ether. The aqeuous phase is acidified to Congo Red by concentrated hydrochloric acid under icecooling. The precipitated amide acid is filtered off, washed with a little water, dried in the air, and recrystallized from chloroform. The yield is 18-19 g and the m.p. 120°. 

Little is known about the direct oxidation of amino acid derivatives. Although an a-acetoxy derivative can be prepared from hippuric acid by treatment with lead tetraacetate (99) this reaction is not applicable to N-phthaloyl- or N-benzyloxycarbonyl-glycine. Anodic oxidation of acetamidomalonic acid monoester in alcohol yielded the ot-alkoxy-a-acetamino acetic acid, while in acetic acid the corresponding oc-acetoxy compound was obtained (186). The oxidation of optically active N-salicylidene-alanine cobalt (III) complexes has been studied as a model reaction for enzymatic deamination of a-amino acids, and found to yield the corresponding diastereomeric a-hydroxy alanine complexes (118). 

In 1962, Barltrop et al. were among the first to report a photochemical deprotection reaction of a biologicaUy significant substrate here, glycine was released from N-benzyloxycarbonyl glycine ... 

N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-alanyl-L-threonyl-L-leucyl-L-alanine p-nitrobenzyl ester)-4-oyl]-N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-alanyl-L-threonyl-L-leucyl-L-alanyl-L-serine p-nitrobenzyl ester)-4-oyl]-N-[N-(benzyloxycarbonyl)-L-aspart-1 -oyl-(glycine ethyl ester)-4-oyl -N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(glycyl-L-serine methyl ester)-4-oyl]-... 

Cl ii X H5Ca 0 N C00CH3 N-Benzyloxycarbonyl- 2-chlor-glycin- metkylester 0 OH II x HsCi O N COOCHj + soc iz, ch2ci2 5... 

Butyllithium, 56 Organozinc reagents, 220 3-Trimethylsilyl-l-propyne, 329 Cross-coupling of alkyl + vinyl groups Iodosylbenzene, 151 Methyl N-benzyloxycarbonyl-a-chloro-glycinate, 186... 

Although CDI was applied as early as 1972 as reagent for the esterification of starch and dextran, it has only scarcely been used up to now. Its renaissance during the last few years may be due to the fact that it became an affordable commercially available product. Among the first attempts for the esterification of polysaccharides via CDI is the binding of amino acids onto dextran. Besides CDI, -(thiocarbony diimidazole can be utilised to obtain the corresponding imidazolide [198]. The amino acids bound via this path are glycine, L-leucine, L-phenylalanine, L-histidine and L-alanyl-L-histidine. They are protected with N-trifluoroacetyl, N-benzyloxycarbonyl... 

Related Reagents. l-Benzoyl-2-r-butyl-3,5-dimethyl-4-imi-dazolidinone (2S,4S)-3-Benzoyl-2-/-butyl-4-methyl-1,3-oxazo-lidin-5-one N-Benzyloxycarbonyl-t-serine p-Lactone N-r-Buto-xycarbonyl-N-methylaminomethyllithium (R)-2-r-Butyl-6-methyl-4H-l, 3-dioxin-4-one N, N-Diethylaminoacetonitrile Ethyl N-(Diphenylmethylene)glycinate Ethyl Isocyanoacetate Methyl ot-Phenylglycinate... 

Synthesis of N-benzyloxycarbonyl-lysine-glycine methyl ester. 

HsC2OOC-CH2-NH—CO-CH-(CH2)2-CO-NH 1 1 H5C6-CH2-O-CO-NH H5ce-NH 50%ige H3C-COOH, MnOa 25 0,5 N-Benzyloxycarbonyl-a-L-glutamyl- glycin-ethylester 82 426... 

An equimolar soln. of glycine isopropyl ester hydrochloride and D-alanine methyl ester in methanoll 3 M tris(hydroxymethyl)aminomethane containing a little 2-mer-captoethanol adjusted to pH 9.5 with 10 MNaOH, 0.5 eqs. of N-benzyloxycarbonyl-phenylalanine methyl ester and a little (crude) papain added successively, the mixture shaken for 1 min, methyl isobutyl ketone added, and stirred vigorously at room temp, for 12 h - Z-Phe-Gly-D-Ala-OMe. Y 57%. A 2-fold increase in yield was observed with methanol as cosolvent compared with dioxane. The method appears to be quite... 

Benzyloxycarbonyl-glycyl-prolyl-leucine, 42B, 370 N-(Benzyloxycarbonyl)prolylleucine ethyl ester, 44B, 444 t-Amyloxycarbonyl-L-prolyl-L-prolyl-L-proline, 40B, 462 Cycloheptasarcosyl monohydrate, 41B, 556 N-Acetyl-bis(dehydrophenylalanine)-glycine, 4IB, 556 n, N-(Bromoacetyl)-L-phenylalanyl-L-phenylalanine ethyl 501... 

Peptides. A mixture of N-benzyloxycarbonyl-L-phenylalanine, ethyl glycinate hydrochloride, triphenylphosphine, bromotridiloromethane, and ethyldiisopropyl-amine refluxed 3 hrs. in tetrahydrofuran ethyl N-benzyloxycarbonyl-L-phenyl-alanylglycinate. Y 85%. F. e. and procedure, also with CCI4 instead of CBrClg, s. L. E. Barstow and V. J. Hruby, J. Org. Chem. 36, 1305 (1971). 

Base catalyzed formation of hydantoins is not limited to blocked dipeptides, it can take place in derivatives of longer chains as well if they are blocked with the benzyloxycarbonyl group at the N-terminus and contain glycine as the second residue in their sequence. 

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