Protecting group-minimized

M Englehard, RB Merrifield. Tyrosine protecting groups. Minimization of rearrangement to 3-alkyltyrosine during acidolysis. (O-cyclohexyltyrosine) J Am Chem Soc 100, 3559, 1978. 

Carbamates can be used as protective groups for ammo acids to minimize race-mization in peptide synthesis. Raccmi/ation occurs during the base-catalyzed coupling reaction of an W-protected, catboxyl-uc ivated amino acid, and takes place in the intermediate oxazolone that foro S readily from an N-acyl protected amino... 

To minimize racemization, the use of nonpolar solvents, a minimum of base, low reaction temperatures, and carbamate protective groups (R = O-alkyl or O-aryl) is effective. (A carbamate, R = O-r-Bu, has been reported to form an oxazolone that appears not to racemize during base-catalyzed coupling.) ... 

Synthesis of a peptide of prescribed sequence requires the use of protecting groups to minimize the number of possible reactions. 

To minimize racemization, the use of nonpolar solvents, a minimum of base, low-reaction temperatures, and carbamate protective groups (R = O-alkyl or O-aryl) are effective. 

The Hoc group was developed for tryptophan protection to minimize alkylation during BOC-mediated peptide synthesis. It is introduced with the chloroformate (NaOH, CH2CI2, Bu4N HS04 ) and can be cleaved with HF without the need to include thiols in the cleavage mixture. 

Minimize derivatives. Syntheses should be designed with minimal use of protecting groups to avoid extra steps and reduce waste. 

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. 

The use of protecting groups in the synthesis was minimized by utilizing the N-picolinyl and N-acetyl groups not only as structural components of 1 but also to tune the reactivity of the intermediates. 

JP Tam, TW Wong, MW Reimen, FS Tjoeng, RB Merrifield. Cyclohexyl ester as a new protecting group for aspartyl peptides to minimize aspartimide formation in acidic and basic treatments. Tetrahedron Lett 4033, 1979. 

A Karsltrom, A Unden. Design of protecting groups for the P-carboxylic group of aspartic acid that minimize base-catalyzed aspartimide formation, (dimethylpentyl) Int J Pept Prot Res 48, 305, 1996. 

CC Yang, RB Merrifield. The P-phenacyl ester as a temporary protecting group to minimize cyclic amide formation during subsequent treatment of aspartyl peptides with HF. J Org Chem 41, 1032, 1976. 

A Karsltrom, A Unden. A new protecting group for aspartic acid that minimizes piperidine-catalyzed aspartimide formation in Fmoc solid phase peptide synthesis. (3-methylpent-3-yl) Tetrahedron Lett 37, 4234, 1996. 

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