N-Boc-protected amino acids

Although these Boc derivatives underwent methylation with poor selectivity (compared to 3-amino-N-benzoyl butanoates [106] and Z-protected methyl 4-phen-yl-3-aminobutanoate [107]), epimers were succesfully separated by preparative HPLC or by flash chromatography. However, saponification of the methyl ester caused partial epimerization of the a-stereocenter and a two-step (epimerization free) procedure involving titanate-mediated transesterification to the corresponding benzyl esters and hydrogenation was used instead to recover the required Boc-y9 -amino acids in enantiomerically pure form [104, 105]. N-Boc-protected amino acids 19 and 20 for incorporation into water-soluble /9-peptides were pre-... 

The methodology was successfully extended to a one-pot total synthesis of complex heterocyclic systems such as pyrazino [2,1-b] quinazolines 79, encountered in nature as alkaloids 80-82 (Scheme 50) [125]. To assemble the pyrazino[2,l-fo]quinazoline core, N-Boc protected amino acid 76 was employed instead of carboxylic acid 72 (Scheme 49) in the synthesis of the corresponding intermediate benzoxazinones 77. The subsequent reaction with an amine moiety of another amino acid ester 78 was accompanied by concomitant cleavage of the N-Boc protecting group and diketopiperazine-like cyclization (for the one-pot deprotection-cyclization reaction of N-Boc dipeptide esters to afford 2,5-piperazinedione under microwave dielectric heating, see [128]) to afford the target heterocycle 79. Hence, the total... 

There are examples of the use of supported carbodiimide 2 (R = Cy) for the formation of N-hydroxybenzotriazole (HOBt)-derived active esters from N-Boc-protected amino acids (see below), which have been subsequently employed in coupling reactions for the synthesis of dipeptide p-nitroanilides and dipeptide diphenyl phosphonates [12, 13]. Such HOBt-active esters have also been generated from pyrazinone-derived acids using 2 (R = Cy) [14], as well as from difluorophenyl acetic acids [15] for further amidation reactions in the parallel synthesis of tissue factor Vila inhibitors. 

A quantitative yield of L-alanine NCA was reported starting from the N-Boc-protected amino acid and PCI3 at 0 °C in dichloromethane [862]. 

Scheme 12-5 Schematic presentation of the synthesis of thiolactone peptide Xni with N-Boc protected amino acids (modified fi-om [36])...

In another context, Guo and co-workers have used a combination of a chiral thiourea, an achiral N-Boc-protected amino acid, and a chiral phosphoric acid to promote a remarkable enantioselective three-component tandem reaction occurring between an aldehyde, a 3-indolylmethanol compound, and an iV-benzyl-protected indole. The process began with the ot-alkylation of the aldehyde with the 3-indolylmethanol catalysed by the... 

Couple each amino acid by removing (TFA) the Boc group from the N terminus, then add the next Boc-protected amino acid with DCC. 

The N-hydroxypyridine-2-thione esters of Boc-protected amino acids undergo decarboxylation on photolysis in the presence of a hydrogen-atom-transfer reagent such as t-butyl mercaptan in 80-95% yield. Decarboxylation of the side-chain carboxy groups of suitably protected aspartic and glutamic acids can also be effected, but yields are lower (50-80%). ... 

In amino acid and peptide chemistry, the di-ferf-butyl dicarbonate (BocaO) is an extensively used reagent for the clean and rapid Boc-protection of amine functionalities.It is also an efficient ferf-butoxycarbonylating agent for alcohols, thiols, and carbon nucleophiles, and it has been used for the conversion of amines into isocyanates, carbamates, and urea derivatives.The reaction of amino acids with chloroformates to produce N-urethane-protected amino acids if not performed under optimal conditions is accompanied by the formation of N-protected oligomers this has been well documented in the case of and... 

As discussed in Section IV, photolysis is a mild cleavage method that is attractive for combinatorial drug discovery because products can be released into neutral aqueous solution suitable for direct screening. Amine analogues of the hydroxyl resins described earlier have been reported. Thus, (aminomethyl)-6>-nitrobenzyl supports 7n have been reported on which short peptide amides could be synthesized with cleavage occurring upon irradiation at 350 nm in the presence of ammonia [323]. 2-Nitrobenzhydryl (NBHA) supports 7o have also been used for peptide amide assembly using Boc-protected amino acids. The anchor was unaffected by 4 N HCl-dioxane... 

Phenacyl esters of various N-a-Boc-, N-a-Cbz- or N,N-dimethylamino-protected amino acids and dipeptides can be cleaved to the corresponding carboxylic acids on heating with bis(tributyltin)oxide in aprotic solvents [Scheme 6J2]P There is no racemisation of the amino acid and peptide products. However there are some limitations to the method removal of tin residues from the product can diminish the yield and the Cbz group (but not a Boc) may undergo competitive cleavage. 

The enantiomers of 563 were obtained by chromatography on (R,R)-Whelk 01 and employed in enantioselective fluorosensing of N-f-Boc-protected amino acids (06JOC2854) and chiral carboxylic acids... 

The peptidyl resin is prepared by standard Fmoc solid phase procedures on 3-(AF methoxyamino)propionamido functionalized resin. 3-terminal amino acid residue can be introduced by direct coupling of the appropriate Boc-protected amino acid or by capping the terminal residue with B0C2O. 

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