Reaction with amino acid esters

Conversion of the isolated A-TBDMS carboxylic acid 111 to the active ester and reaction with amino acid esters yielded after desilylation the /3-sultam peptides 112 and 113. Removal of the protecting groups was also possible with benzylic esters but attempted hydrolysis of alkyl ester groups resulted in hydrolysis of the /3-sultam ring. Catalytic hydrogenation of the benzyl esters afforded the N-silylated /3-sultam peptides 114 in quantitative yields (Scheme 34) <2004M979>. 

Asymmetric cycloaddition reactions with amino acid esters as chiral auxiliaries 91G227. 

The non-urethane type A -Trt amino acid fluorides have been synthesized and were shown to undergo clean reaction with amino acid esters without loss of configuration. 

Scheme 5.9 Ring-opening reaction with amino acid esters.

Reaction with Phosgene. This reaction of amino acid esters is used for preparing the corresponding isocyanates, especially lysine diisocyanate [4460-02-0] (LDI). LDI is a valuable nonyellowing isocyanate with a functional side group for incorporation in polyurethanes. 

F Weygand, W Steglich, X Boracio de la Lama. On the sterical course of the reaction of oxazol-5-ones with amino-acid esters. Tetrahedron Suppl 8, part 1, 9, 1966. 

FMF Chen, NL Benoiton. Identification of the side-reaction of Boc-decomposition during the coupling of Boc-amino acids with amino acid ester salts, in JA Smith, JR Rivier, eds. Chemistry and Biology. Proceedings of the 12th American Peptide Symposium, Escom, Leiden, 1992, pp. 542-543. 

Y. Kurono, T. Furukawa, T. Tsuji, K. Ikeda, Esterase-Like Activity of Human Serum Albumin. VI. Reaction with p-Nitrophenyl Glycinate , Chem. Pharm. Bull. 1988, 36, 4068-4074 Y. Kurono, I. Kushida, H. Tanaka, K. Ikeda, Esterase-Like Activity of Human Serum Albumin. VIII. Reaction with Amino Acid p-Nitrophenyl Esters , Chem. Pharm. Bull. 1992, 40, 2169-2172. 

Y. Kurono, I. Kushida, H. Tanaka, K. Ikeda, Esterase-Like Activity of Human Serum Albumin. VIII. Reaction with Amino Acid p-Nitrophenyl Esters , Chem. Pharm. Bull. 1992, 40, 2169-2172. 

Reaction with all kinds of alkylamines and arylamines and with amino acid esters easily leads to replacement of the N-NO2 group. As can be expected, when chiral amino acid esters are used as reagents, the reaction occurs with retention of the configuration (Scheme III.30). See also the discussion on similar reactions with A-nitroimidazoles in Section III,A,5. 

Reactions of this type provide one of the major routes to the commercially important l,4-benzodiazepin-2-one system (156) via the reaction of substituted o-aminobenzoph-enones (155) with amino acid esters (68CRV747, p. 756). This synthesis allows the easy preparation of 3-substituted products by the use of readily available a-substituted amino acids, e.g. the CNS active Tranxene (156 Y = C1, Ar = Ph, R1 = CC>2H) by using aminomalonic ester. Similar reactions have been carried out using other three-atom components, e.g. 2-bromoethylamine (77MIP51800) and ketenimines (77JHC99). 

Active OBt esters of o-Abz and of p-Abz have been prepared by activation of H-Abz-OH with DCC. 24 These esters react with amino acid esters within 10 min to 1 h, whereas the corresponding -ONp esters require 1-10 days. The ortho-isomer was consistently more reactive than the para-isomer. The -OSu and -OOBt active esters of o-Abz are reported to be more reactive than the -OPhth esters. 35 Reaction of o-Abz-OSu with H-Ac3c-OH resulted in 65% coupling after 24 h. 24 ... 

Thiol esters. DPPA in combination with triethylamine promotes coupling of carboxylic acids and thiols to form thiol esters, R COSR2 (50 95% yield). Only slight racemization occurs during reaction with amino acids.2... 

The main class of bioerodible polyphosphazenes that have been developed so far are polymers with amino acid ester side groups. They are prepared by the reaction of poly(dichlorophosphazene) with the ethyl or propyl esters of amino acids such as glycine, alanine, phenylalanine, and so on (reaction (57)).196 The ethyl or propyl ester of the amino acid must be used as the nucleophile in this reaction for two reasons. First, a free carboxylic acid unit would provide a second nucleophilic site that could lead to... 

Metal chelating amino acid derivatives of cellulose were recently obtained via modification of cellulose with 2,4-toluenediisocyanate, followed by treatment with amino acid ester derivatives [58,59]. Diisocyanates are able to crosslink cellulose chains and/or to yield reactive cellulose isocyanate, depending on the reaction conditions. Sato and his coworkers [60] examined the optimum conditions for the reaction between cellulose and 2,4-toluenediisocyanate and succeeded in introducing 0.30 mol of free isocyanate group per glucose unit. Cellulose isocyanate was further converted into isothiocyanate [61]. This derivative has also been synthesized by condensation of cellulose with 2,4-diisocyanototoluene, followed by hydrolysis and thiophosgene treatment [61]. 

Reaction with amino acid derivatives N-Protected amino acid esters substituted by I, Br, or OTs at the y-position undergo substitution reactions with lithium dialkyl cuprates without deteetable racemization. 

All of the A -Trt amino acid fluorides listed in Table 6 are soluble in diethyl ether, with the exception of Trt-pGlu-F.t The fluorides undergo aminolysis with amino acid esters and amides without loss of configuration, although relatively slowly due to the steric hindrance resulting from the bulky Trt group. For example, the reaction of Trt-pGlu-F with H-His-OMe and Trt-Ile-F with H-Val-OBzl required 30 minutes and 6 hours respectively.t ... 

The propensity of NCAs to polymerize has substantially limited their routine use for sequential peptide synthesis. Upon first reports on the reaction of NCAs with amines or amino acid esters,Baileyt provided a definitive study of the reaction of amino acid esters with a variety of NCAs at —65 °C to give A-carbamoyl dipeptides which on warming to room temperature liberated carbon dioxide to give the free amino dipeptide. The mixture is then recooled to —65°C and condensed with a second NCA to give the tripeptide (Scheme 11). 

Reaction of Amino Acid Esters with Carbodiinudes... 

Fullerene amino acid derivatives have merited special attention in relation with the biological application [275-280], The photochemical reactions of Ceo with amino acid esters have been utilized to obtain fullerene amino acid derivatives [281,282]. For example, the photochemical addition of iminodiacetic methyl ester to Ceo provides a pyrrolidine ring-fused fullerene carboxylate, C6o(MeOOCCHNHCHCOOMe) [281]. Although the mechanistic detail has yet to be elucidated, a possible sequence... 

Hydrophobic interactions may also serve to purify products of combinatorial syntheses. As an example, penta-O-lauroyl-l-thio-p-galactose was subjected to a Michael addition to a,p-unsaturated ketones or to alkylation by a-chloro ketones followed by reduction of the keto groups or by reductive alkylation with amino acid esters. The reaction mixtures were passed through Cl8 silica gel, whereby the desired products were adsorbed while unwanted products were washed away. Desorption was carried out with pentane, and the hydrophobic labels were removed with methanolic sodium methoxide.The methyl laurates were finally separated from the desired products by chromatography on silica... 

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