N"-tert.-Butyloxycarbonyl

A solution of 3.55 parts of L-trypTtophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide trifluoroacetate in 30 parts of dimethylformamide is cooled to 0 C, and 1.01 parts of tri-ethylamine are added. The mixture is stirred while 1.84 parts of N-tert-butyloxycarbonyl-(3-alanine 2,4,5-trichlorophenyl ester are added at 0 C. The reaction mixture is kept at 0°C for 48 hours and then at 20°-23°C for 24 hours. The mixture is added to a mixture of 100 parts of ice-water, 0.37 part of concentrated hydrochloric acid (SG 1.18), 1.2 parts of acetic acid and 20 parts of ethyl acetate. The mixture is stirred for 15 minutes at 0°-10°C and is then filtered. The solid residue is washed with water and then with ethyl acetate, and is dried at 40°-50°C under reduced pressure. There is thus obtained N-tert-butyloxycarbonyl-)3-alanyl-L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide, MP 213°C with decomposition. 

It has been found that the tris(tert-butyloxycarbonyl) protected hydantoin of 4-piperidone 2, selectively hydrolyses in alkali to yield the N-tert-butyloxycarbonylated piperidine amino acid 3. The hydrolysis, which is performed in a biphasic mixture of THF and 2.0M KOH at room temperature, cleanly partitions the deprotonated 4-amino-N -(tert-butyloxycarbonyl)piperidine-4-carboxylic acid into the aqueous phase of the reaction with minimal contamination of the hydrolysis product, di-tert-butyl iminodicarboxylate, which partitions into the THF layer. Upon neutralization of the aqueous phase with aqueous hydrochloric acid, the zwitterion of the amino acid is isolated. The Bolin procedure to introduce the 9-fluorenylmethyloxycarbonyl protecting group efficiently produces 4.8 This synthesis is a significant improvement over the previously described method9 where the final protection step was complicated by contamination of the hydrolysis side-product, di-tert-butyl iminodicarboxylate, which is very difficult to separate from 4, even by chromatographic means. 

Protecting group abbreviations are as follows JV-benzyloxycarbonyl (Z), N-tert-butyloxycarbonyl (Boc), tert-butyl ether (Bu ), and S-tert-butyl (Bu ). 

Die entsprechenden ent-Formen mit (5/ ,6S)-Konfiguration werden analog erhalten1. So-wohl die N-tert.-Butyloxycarbonyl- wie der N-Benzyloxycarbonyl-2-oxo-morpholine sind in beiden optischen Formen auch im Handel erhaltlich. 

HsCj-CO-CHz-CO-OCzHs co-ch3 -CH 1 COOC2H5 3-Acetyl-N-tert-butyloxycarbonyl-asp araginsaure-l-tert.-butylester-4-ethylester 48 Ol 1... 

Alanatc Pentafluoro-phenyl-N-tert.-Butyloxycarbonyl- ElOb, 583f. (OH - O-CO-R)... 

Azotomycin is anticancer antibiotic produced by Streptomyces ambofaciens. Total sythesis of it from y-benzyl-N-tert-butyloxycarbonyl-L-glutamic acid (y-OBzi-N-Boc-L-Glu) has been accomplished in nine steps. The mixed carbonic anhydride method was chosen for peptide bond formation. Commerically available y-OBzi-N-Boc-L-Glu was esterified with ethereal diazomethane, deprotected with trifluoroacetic acid-methylene chloride (1 1), and converted to hydrochloride y-benzyl-L-glutamic acid a-methyl ester (y-OBzi-L-Glu-a-OMe HCI) by treatment with dry hydrogen chloride in ethyl ether, MP 129°-135°C (dec.) [a]D25= + 13.3° (CHCI3). 

N-tert.-Butyloxycarbonyl- XV/1, 125 (N-Acylierung) E4, 158 (Anhy-drid + Amin), 173 (Umamidie-rung)... 

N-tert.-Butyloxycarbonyl- -anhydride XV/2, 262, 266 N-tert.-Butyloxycarbonyl-N-methyl-E4, 169 (N-Alkylier.) N-Carbonyl- -(4-nitro-benzylester) XV/2, 185... 

N-(tert.-Butyloxycarbonyl)-0-(2,6-dinitro-phenyl)- E16a, 256 (O-Arylier.)... 

Glycinate tert.-Butyl N-(tert -Butyloxycarbonyl)-2-bromo-E21b, 1966 (H -> Br)... 

L-Alanin N-tert.-Butyloxycarbonyl- -tert.-butyJester E19a, 243 (3-COOH 3-H)... 

Nitron N-(tert.-Butyloxycarbonyl-methyl)-C-phenyl- El4b, 1434 (aus Oxim)... 

N-tert. Butyloxycarbonyl-N-methoxypropionic Cleavage Product after cleavage ... 

In the SAPPHO process, the N-tert-butyloxycarbonyl (N-t-BOC), the N-allyloxycarbonyl (N-ALLOC), and the N,N-diallyl can be used for the protection of the alpha amino function. The functional side chains can be protected by different classical orthogonal protecting groups. 

N-tert.-Butyloxycarbonyl-O-tert.-butyl- 1281 N-Cydohexyl- 179.1081 N-C yclohexyliden- 179, 1081 (a-D)-N,N-Dimelhyl-0-beiiz vl- 1282 Ileptyliden-(4)- 1458 N-(4-Hydroxy-cydooetyliden)- 718 N-Nitroso-N-cydohexyl- 179... 

In the procedure presented here, the phthaloyl group is chosen as an amino protecting group to avoid internal amine participation.13 Amine diprotection is necessary since the same reaction conducted on the N-benzyloxycarbonyl (NHCbz) and the N-tert-butyloxycarbonyl (NHBoc) analogues did not led to clean a-chlorination but rather to unidentified products. This protection was performed using a standard procedure.14... 

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