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. 

A CONVENIENT PREPARATION OF AN ORTHOGONALLY PROTECTED C ,C -DISUBSTITUTED AMINO ACID ANALOG OF LYSINE l-tert-BUTYLOXYCARBONYL-4-((9-FLUORENYLMETHYLOXYCARBONYL)AMINO)-PIPERIDINE-4-... 

Triturating with chloroform is necessary to successfully remove a trace amount of 1-tert-butyloxycarbonylpiperidine-4-spiro-5 -(r-tert-butyloxycarbonyl)-hydantoin. 

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 ). 

Scheme 3.13 CM to form tetra-substituted olefins (Boc = tert-butyloxycarbonyl)...

Rich DH, Gurwara SK. Preparation of a new o-nitrobenzyl resin for solid-phase synthesis of tert-butyloxycarbonyl-protected peptide acids. J Am Chem Soc 1975 97 1575-1579. 

A nitrogen-protective benzyl group was hydrogenolytically removed and replaced by a tert-butyloxycarbonyl moiety in a single operation. The protected compound and (Boc)20 in MeOH and 10% Pd/C were treated for 48 hours under 3 atm H2 (Scheme 4.79).325,326... 

Crawford et al.24 explored the possibility of SHG-CD and SHG-ORD to study biological samples. They studied the dipeptide (tert-butyloxycarbonyl)tryptophanyltryptophan adsorbed at an air-water and a heptane-water interface. A dye laser that operated in the wavelength region 550-580 nm was used to record SHG-CD and SHG-ORD spectra. The SHG spectra from the LL and DD enantiomers showed equal but opposite dependences on the handedness of the fundamental laser beam and the DL diastereoisomer gave rise to different SHG spectra.24... 

The noteworthy advantages of the allyl ester are (a) it is readily introduced into amino acids (b) after isomerization (to 1-propenyl) by a palladium(O) catalyst it may be removed under weakly acidic or basic and neural conditions (32), even if sulfur-containing amino acids are present (34) (c) it shows orthogonal stability to the tert-butyloxycarbonyl and 9-fluorenylmethoxy-carbonyl groups (10) and (d) it is not affected by the hydrogen fluoride-pyridine complex (35). 

GE Reid, RJ Simpson. Automated solid-phase peptide synthesis use of 2-(17f-ben-zotriazol-l-yl)-l,l,3,3-tetramethyluronium tetrafluoroborate for coupling of tert-butyloxycarbonyl amino acids. Anal Biochem 200, 301, 1992. 

RE Reid. Solid phase peptide synthesis. A study on the effect of trifluoroacetic acid concentration on the removal of the tert-butyloxycarbonyl protecting group. J Org Chem 41, 1027, 1976. 

L Moroder, A Hallett, E Wiinsch, O Keller, G Wersin. di-tert-Butyldicarbonat — an advantageous reagent for introduction of the tert-butyloxycarbonyl protecting group. Hoppe-Seyler s Z Physiol Chem 357, 1651, 1976. 

JW Scott, D Parker, DR Parrish. Improved syntheses of Ne-(tert-butyloxycarbonyl)-L-lysine and Na-(benzyloxycarbonyl)-Ne-(fert-butyloycarbonyl)-L-lysine. Synthetic Commun 11, 303, 1981. 

Tesalova, E., Bosdkovi, Z., and Pacakova, V., Comparison of enantioselective separation of A -tert-butyloxycarbonyl amino acids and their non-blocked analogues on teicoplanin-based chiral stationary phase, J. Chromatogr. A, 838, 121, 1999. 

Tesafova, E., Bosdkovd, Z., and Zuskova, L, Enantioseparation of selected iV-tert-butyloxycarbonyl amino acids in high-performance liquid chromatography and capillary electrophoresis with a teicoplanin chiral selector. J. Chromatogr. A, 879, 147, 2000. 

Amino group protection may be achieved by converting the amine into its Al-tert-butyloxycarbonyl (tBOC or just BOC) derivative, by reaction with di-tert-butyl dicarbonate. This reagent should be considered as a variant of a carboxylic acid... 

Racemic cw-l-amino-2-phenylcyclohexanecarboxylic acid 693 can be prepared by Diels-Alder reaction of (Z)-4-benzyhdene-2-phenyl-5(47/)-oxazolone 621 and butadiene in an analogous manner. Coupling A-tert-butyloxycarbonyl-L-proline with 693 yielded diastereomeric dipeptides that were separated chromatographi-cally. The behavior of the individual dipeptides was studied as a means to effect p-tum modulation by such cyclohexane analogues of phenylalanine. ... 

Recently, the cyclopropanation of (Z)-4-benzyIidene-2-phenyl-5(4//)-oxazolone 621 with phenyldiazomethane was reported to give the spirocyclopropane, rac- 21 in very high yield. Subsequent ring opening and hydrolysis of rac- 21 generated frani-l-amino-2,3-diphenyl-l-cyclopropanecarboxylic acid, rac-828 (cadiPhe) (Scheme 7.256). This new, constrained phenylalanine analogue induces a y-tum in the sohd state when incorporated into model dipeptides. The enantiomers of the Al-Boc (Boc = tert-butyloxycarbonyl) methyl ester of 828 have been resolved by HPLC. 

Das Hydrochloric von N(a)-Benzyloxycarbonyl-N jr)-benzyloxymethyl-histidin-methylester kann entweder aus iV( t)-Acetyl-N(tx)-benzyloxycarbonyl-histidin-methylester (R1 = CH, 88%) oder aus N(a)-Benzyloxycarbonyl-N(i)-tert.-butyloxycarbonyl-histidin-methylester [R1 = Q-C(CH3)3 48%] durch Umsetzung mit Benzyloxy-chlor-methan hergestellt werden883. 

Durch Erhitzen von 4(5)-Azidocarbonyl-imidazol in tert.-Butanol wird in 41 % Ausbeute 4(5)-tert.-Butyloxycarbonylamino-imidazol erhalten998. Analog fiihrt die Umsetzung von 4(5)-Hydrazinocarbonyl-l-methyl-imidazol mit Natriumnitrit/Salzsaure nach anschlieBender Ther-molyse des so erhaltenen Carbonsaure-azids in tert.-Butanol zu 5-tert.-Butyloxycarbonyl-amino-I-methyl-imidazol (88%)999 ... 

Mit N(a)-tert.-Butyloxycarbonyl-2-diazo-L-histidin-methylester gelingt auch die Isolierung der 2-Diazo-Verbindung eines Histidin-Derivates1069. 5-Aminocarbonyl-4-diazo-imidazol reagiert mit Hydrazin zu 5(4)-Aminocarbonyl-4(5)-azido-imidazoli06 1069. 

Wasserfreies Zinkbromid in Dichlormethan ist ein mildes Reagenz, um tert. Butyloxycarbonyl-Schutzgruppen von sek. Aminen abzuspalten. (BOC-Gruppen an prim. Aminen bleiben ver-schont.) Eine 1-BOC-Schutzgruppe wird auf diese Weise (Zinkbromid 20° 4 h Argon) entfernt... 

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