Benzoyl-L-leucine

If, however, the /7-nitrophenyl ester of iV-henzoyl-L-leucine is treated with 1-methyl-piperidine in chloroform for 30 min and then coupled with glycine ethyl ester, the dipeptide isolated is almost completely racemic. Furthermore, treatment of the p-nitrophenyl ester of iV-benzoyl-L-leucine with 1-methylpiperidine alone leads to the formation of a crystalline material, C13H15NO2, having strong IR bands at 1832 and 1664 cm . Explain these observations, and suggest a reasonable stmcture for the crystalline product. 

Enantiomerically pure dipeptide is obtained when the 4-nitrophenyl ester of N-benzoyl-L-leucine is coupled with ethyl glycinate in ethyl acetate. If, however, the leucine ester is treated with 1-methylpiperidine in chloroform for 30 min prior to coupling, the dipeptide in nearly completely racemized. Treatment of the leucine ester with 1-methylpiperidine leads to formation of a crystalline material of composition C13H15NO2, which has strong IR bands at 1832 and 1664 cm Explain how racemization occurs and suggest a reasonable structure for the crystalline material. 

The first model (Williams and Young 1963) was based on coupling of benzoyl-L-leucine to glycine ethyl ester. The specific rotation of the crude product was used... 

Optically pure dipeptide is obtained when the p -nitrophenyl ester of N-benzoyl-L-leucine is coupled with glycine ethyl ester in ethyl acetate ... 

Di-(2-pyridyl) disulphide has found a novel use as oxidant in peptide synthesis iV-benzoyl-L-leucine is coupled to glycine ethyl ester to give the protected dipeptide, when triphenylphosphine and the disulphide are added, formation of triphenyl phosphite and pyridine-2(li7)-thione balancing the equation. ... 

In plastein synthesis the free energy of formation of the peptide bonds is small, as attested to by the reversal of hydrolysis merely by concentrating certain enzymatic hydrolytic products the synthetic product is insoluble, which tends to drive the reaction toivards synthesis. In these two respects plastein formation resembles reactions of the type benzoyl-L-leucine - - L-leucine anilide to benzoyl-L-leucyUeucine anilide. 

CCI4 added dropwise at -15° during 5-30 min. to a soln. of N-benzoyl-L-leucine, ethyl glycinate, and 3 moles tris(diethylamino)phosphine in tetrahydrofuran, and allowed to stand overnight at room temp. ethyl N-benzoyl-L-leucylglycinate. Y 60-85%. F. e. and phosphorous compds., also with 1 mole phosphorous compd. and 2 moles of a different base, and with CBr4, s. S. Yamada and Y. Takeuchi, Tetrah. Let. 1971, 3595 s. a. T. Wieland and A. Seeliger, B. 104, 3992 (1971). 

Benzoyl-L-leucine + n-Leucine anilide-------- Benzoyl-L-leucine anilide... 

The free energy of formation of the peptide bonds in plastein synthesis must be small this is attested to by the possibility of inducing peptide bond synthesis merely by concentrating an enzymatic hydrolyzate. The synthetic product is practically insoluble and this drives the reaction toward synthesis. It is in these two respiects that plastein formation resembles reactions of the type benzoyl-L-leucine + L-leucine anilide —> benzoyl-L-leucylleucine anilide. 

Another dibenzoate of an aminoacid amino alcohol is hypothallin, (-)-A-benzoyl-L-phenyl-alaninyl-A -benzoyl-L-leucinate (10) from the lichen Schismatomma hypothallimm 402). It was synthesized by condensation of (-)-A -benzoxycarbonyl-L-leucine and (-)-A -benzoyl-L-phenylalaninol in the presence of A, A -carbonyldiimidazole and subsequent debenzoxycarbonylation and benzoylation (see Scheme 23). 

OnoMo, A.B., Gesser, J.C., Joussef, A.C., Nome, F. Reactions of N-(o-carboxy-benzoyl)-L-leucine intramolecular catalysis of amide hydrolysis and imide formation by two carboxy groups. J. Chem. Soc. Perkin Trans. 2. 2001, 1863-1868. 

The above reagent allows the coupling in high yield of acylamino acids with amino esters in a single operation and without racemization. - E N-Ethoxy-carbonyl-2-ethoxy-l,2-dihydroquinoline added to a soln. of N-Benzoyl-L-leucine and ethyl glycinate in tetrahydrofuran, and stirred 6-7 hrs. at room temp. ethyl N-benzoyl-L leucylglycinate. Y 95%. F. e. s. B. Belleau and G. Malek, Am. Soc. 90, 1651 (1968). 

Benzoyl-L-leucine o-hydroxyphenyl ester and ethyl glycinate dissolved at room temp, in dioxane, and the product isolated after 2 hrs. crude ethyl benzoyl-L-leucylglycinate. Y 96%. - No racemization occurs. The activating o-hydroxyl can be blocked and reactivated by use of O-benzjd as blocking group. F. e. s. J. H. Jones and G. T. Young, Soc. (G) 1968, 436. 

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