Boc-D-Leu

Scheme 15.3 Total synthesis of malformin C (1215). Reagents and conditions a) Boc-D-Leu-OH, EDC-HCl, HOBt, DIPEA, CH2CI2, rt, 98% b) 4 M HCl/dioxane, 0°C c) Emoc-L-Val-OH, EDC-HQ, HOBt, DIPEA, CH2CI2/DMF (4 1), it d) H2, Pd(OH)2, EtOAc, 40°C, 86% over three steps e) CS2CO3, allyl bromide, DMF, rt 1) piperidine, CH2O2, 0°C, 93% over two steps g) Fmoc-D-Cys(Tr)-OH (1210), EDC HC1, HOBt, DIPEA, GH2CI2, rt h) piperidine, CBjC 2,0°C, 72% over two steps i) HBTU, HOBt, NMM, CH2CI2/DMF (4 1), it, 93% j) piptaidine, CH2CI2, 0°C k) 1 M NaOH, THE, rt, 81% over two steps 1) HATU, HO At, NMM, GH2a2, 0°C, 69% m) I2, DMF, rt, 85%...

Fmoc-amino acids used as building blocks of testing compounds are as follows Fmoc-Asp(OtBu)-OH, Fmoc-Cys(Trt)-OH, Fmoc-Asn(Trt)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Met-OH, Fmoc-Glu(OtBu)-OH, Fmoc-Lys (Boc)-OH, Fmoc-Ile-OH, Fmoc-His(Trt)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Arg(Pmc)-OH, Fmoc-Phe-OH, Fmoc-Ser(tBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Val-OH, Fmoc-Pro-OH, Fmoc-Trp(Boc)-OH, Fmoc-D-Ala-OH, Fmoc-D-Arg(Pmc)-OH, Fmoc-D-Trp(Boc)-OH, Fmoc-D-Cys(Trt)-OH, Fmoc-D-Asp(OtBu)-OH, Fmoc-D-Glu(OtBu)-OH, Fmoc-D-His(Trt)-OH, Fmoc-D-Gln(Trt)-OH, Fmoc-D-Leu-OH, Fmoc-D-Met-OH, Fmoc-D-Pro-OH, Fmoc-D-Ser(tBu)-OH, Fmoc-D-Lys(Boc)-OH, Fmoc-D-Tyr(tBu)-OH, Fmoc-D-Thr(tBu)-OH, Fmoc-D-Phe-OH, Fmoc-D-Asn(Trt)-OH, Fmoc-3-(4-pyridyl)alanine, Fmoc-D-3-(3-pyridyl)alanine, Fmoc-4-tert-butoxyproline, Fmoc-3-chlorophenylalanine, Fmoc-norleucine, Fmoc-2-cyclohexylglycine, Fmoc-2-aminoisobutyric acid, Fmoc-tranexamic acid, Fmoc-(i ,S)-3-amino-3-(2-furyl)propionic acid, Fmoc-(i ,S)-(6,7-di-methoxy)-l,2,3,4-tetrahydroquinoline-3-carboxylic acid, Fmoc- (R, S)-3-amino-3-(4-hydroxyphenyl)propionic acid, Fmoc-(i ,S)-3-aminovaleric acid, Fmoc-(i ,5 )-3-amino-3-(3,4-dichlorophenyl)propionic acid, Fmoc-isonipecotic acid, Fmoc-(i ,S)-3-amino-3-(3,4-methylenedioxyphenyl)... 

Rodriguez. M.. Heitz. A., and Martinez, J., Carba" peptide bond surrogates. Synthesis of BOC-l-Leu- PlCHj-CHji-L-Phe-OH and BOC-L-Leu- PlCHj-CHjJ-D-Phe-OH through a Homer-Emmons reaction. Tetrahedron Lett., 31, 7319, 1990. 

Fabiola, G.G., Bobde, V., Damodharan, L., Pattabhi, V., and Durani, S. (2001) Conformational preferences of heterochiral peptides. Crystal structures of heterochiral peptides Boc-(d) Val-(D) Ala-Leu-Ala-OMe and Boc-Val-Ala-Leu(D) Ala-OMe-enhanced stability of p-sheet through CH- -O hydrogen bonds, J. Biomol. Struct. Dyn. 18, 579-594. 

Phe, D-Phe and D-Phe ierf-butyl ester. The enzyme was not active toward L-Phe methyl ester, (L-Phe)2 methyl ester, (L-Phe)4, Boc-(L-Phe)4, Boc-(L-Phe)4 methyl ester, (D-VaDa, (D-Leu)2, or (D-Ala)n (n = 2 - 5). These properties indicated that the enzyme is an endopeptidase that acts D-stereospecifically upon peptides composed of aromatic D-amino acids. On the other hand, a dimer was formed when D-Phe methyl ester and D-Phe amide were the substrates. Eight stereoisomers of Phe trimer were synthesized, and their effectiveness as substrates for the enzyme was tested. The enzyme recognized the configuration of the second D-Phe of tripeptides and catalyzed the hydrolysis of the second peptide bond from the N-terminus. The calculated Vmax/Km values for the peptides containing L-Phe were lower than that for (D-Phels, affected by the configuration of the neighboring L-Phe. The enzyme also showed P-lactamase activity toward ampicillin and penicillin G. The calculated Vmax values of the enzyme for b-lactam compounds were about the same as those for (D-Phe)3 and (D-Phe)4, while the Km values were several hundred times larger. On the other hand, carboxypeptidase DD and D-aminopeptidase activities were undetectable. 

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