Cyclization of<i>all</i>-<scp>l</scp>-Pentapeptides by Means of 1-Hydroxy-7-azabenzotriazole-Derived Uronium and Phosphonium Reagents

Ehrlich, Angelika; Heyne, H.-U.; Winter, Rüdiger; Beyermann, Michael; Haber, H.; Carpino, Louis A.; Bienert, Michael

doi:10.1021/jo951108d

Cited by 160 publications

(147 citation statements)

References 30 publications

Supporting

Mentioning

144

Contrasting

Order By: Relevance

“…DMF (1.5 mM) under stirring. DEPBT (3)(4)(5) equiv.) and DIEA (1% v/v) were then added at r.t. and the solution was stirred for an additional 3 d. The solvent was evaporated under reduced pressure, and the crude cyclopeptide was purified by CC and prep.…”

Section: General Procedures 5 (Depbt-mediated Cyclization) (Gp 5) Frementioning

confidence: 99%

“…TLC. 3323m, 3064w, 2984m, 2940m, 1673s, 1594m, 1534s, 1494m, 1452s, 1425m, 1391m, 1361m, 1336m, 1281m, 1244m, 1195m, 1168m, 1125m, 1091m, 1017w, 991w, 760m, 741m 3,179.9,176.1,174.6,169.7 (5s,6 CO); 156.4 (s, CO(urethane)); 144. 8, 143.1, 142.4 (3s, 4 arom.…”

Section: General Procedures 5 (Depbt-mediated Cyclization) (Gp 5) Frementioning

confidence: 99%

“…C); 130. 3,129.2,128.8,128.1,127.4,126.1,126.0,121.0 (8d,18 arom. CH);68.8 (t,CHCH 2 O of Fmoc);61.9 (d,C(2) of Pro);58.3,57.9,57.7 (3s,3 C(2) of 3 Aib); 61.9, 56.4 (2d, C (2) of Pro and C (2) (5) of Pro and C(2) of Gly); 41.2 (q, MeN); 37.7 (t, C (3) of Phe); 31.0 (t, C(3) of Pro); 26.6, 25.6, 25.2 (3q, 6 Me of 3 Aib); 25.5 (t, C (4) 32, H 6.74, N 10.99; found: C 67.32, H 6.78, N 11.04.…”

Section: General Procedures 5 (Depbt-mediated Cyclization) (Gp 5) Frementioning

confidence: 99%

“…Cyclization can also constrain a short amino acid sequence to a turn conformation [2]. In particular, cyclic penta-and hexapeptides have frequently been used as models for reverse turns, although the cyclization of these small peptides is often troublesome [3]. Since peptide bonds possess pronounced π character and preferentially adopt a trans conformation, the linear precursor has the terminal acid and amine functions in remote positions, which is unfavorable for cyclization.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Synthesis of Cyclohexapeptides Containing Pro and Aib Residues.

2005

View full text Add to dashboard Cite

Cyclization reactions on hexapeptides containing several alpha-aminoisobutyric acid (= 2-amino-2-methylpropanoic acid; Aib) residues and the turn-promoting glycine (Gly) and proline (Pro) residues were investigated. Eight linear hexapeptides were synthesized, and their cyclization was attempted with various coupling reagents. The macrolactamization step proved to be difficult since only three hexapeptides could be cyclized. Two of these latter peptides were the linear precursors of the same cyclic hexapeptide, cyclo(Aib-Aib-Phe-Pro-Aib-Gly) (1). Surprisingly, they gave 1 in almost the same yield. Thus, 1 was obtained in 35% yield upon ring closure at the Phe/Pro site by using DEPBT as the coupling reagent, whereas the cyclization at the Aib/Phe site led to 1 in 28 and 34% yield by using PyAOP and DEPC, respectively (DEPBT = 3-[(diethoxyphosphoryl)oxy]-1,2,3-benzotriazin-4(3H)-one, PyAOP = (1H-7-azabenzotriazol-1-yloxy)tripyrroli-din-1-ylphosphonium hexafluorophosphate, DEPC = diethyl phosphorocyanidate). Another cyclic hexapeptide, cyclo(Aib-Aib-Gly-Aib-Pro-Gly) (2) was prepared in 34% yield when DEPC was used in the cyclization step. The solid-state conformation of 1 was established by X-ray crystallography. 2 Cyclization reactions on hexapeptides containing several Aib residues and the turn promoting Gly and Pro residues were investigated. Eight linear hexapeptides were synthesized and their cyclization was attempted using various coupling reagents. The macrolactamization step proved to be difficult since only three of these hexapeptides could be cyclized. Two of these peptides were the linear precursors of the same cyclic hexapeptide, cyclo(Pro-Aib-Gly-Aib-AibPhe) (1). Surprisingly, they gave 1 in almost the same yield. Thus, 1 was obtained in 35% yield upon ring closure at the Phe/Pro site using DEPBT as the coupling reagent, whereas the cyclization at the Aib/Phe site led to 1 in 28 and 34% yield by using PyAOP and DEPC, respectively. Another cyclic hexapeptide, cyclo(GlyAib-Pro-Gly-Aib-Aib) (2) was prepared in 34% yield when DEPC was used in the cyclization step. The solid-state conformation of 1 was established by X-ray crystallography.3

show abstract

Section: General Procedures 5 (Depbt-mediated Cyclization) (Gp 5) Frementioning

confidence: 99%

Section: General Procedures 5 (Depbt-mediated Cyclization) (Gp 5) Frementioning

confidence: 99%

Section: General Procedures 5 (Depbt-mediated Cyclization) (Gp 5) Frementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Synthesis of Cyclohexapeptides Containing Pro and Aib Residues.

2005

View full text Add to dashboard Cite

show abstract

“…The stage was now set for the comparison of macrolactamization step at two sites (Thz/Phe vs. Pro/Ile). After deprotection of the Boc group in 11 and 12 with hydrogen chloride in dioxane and saponification of the methyl ester with lithium hydroxide, macrolactamizations of the resulting two free linear precursors were performed in a DMF solution (0.002 M) by using DPPA (diphenyl phosphorazidate), 8 FDPP (pentafluorophenyl diphenylphosphinate), 9 and HATU [O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate], 10 respectively. The cyclization at the Thz/Phe site proceeded smoothly and the yield by FDPP was higher than those by DPPA and HATU.…”

mentioning

confidence: 99%

Total Synthesis of cis,cis-Ceratospongamide, a Bioactive Thiazole-Containing Cyclic Peptide from Marine Origin

Yokokawa¹,

Sameshima²,

Shioiri³

2001

Synlett

View full text Add to dashboard Cite

Abstract:The first total synthesis of cis,cis-ceratospongamide (1a), isolated from marine source, was accomplished via thiazole synthesis using CMD methodology, DEPC-mediated peptide coupling, macrolactamization, and cyclodehydration. Comparison of the cyclization sites and coupling reagents in the macrolactamization step was also investigated.Key words: ceratospongamide, chemical manganese dioxide (CMD), macrolactamization, cyclic peptide, total synthesis Ceratospongamide is a bioactive thiazole-containing cyclic heptapeptide isolated by Gerwick and co-workers from the Indonesian red alga Ceratodictyon spongiosum and symbiotic sponge Sigmadocia symbiotica.1 This peptide consists of two L-phenylalanine residues, one (L-isoleucine)-L-methyloxazoline residue, one L-proline residue, and one (L-proline)thiazole residue. Interestingly, ceratospongamide is able to be isolated as two stable isomers, which are assigned as cis,cis-and trans,trans-isomers (1a, 1b) of the two proline amide bonds by Gerwick and co-workers (Figure 1). Both compounds show moderate potency in the brine shrimp toxicity assay (LD 50 = 13-19 mM). In addition, trans, exhibits potent inhibition of the expression of a key enzyme in the inflammatory cascade, secreted phospholipase A 2 (sPLA 2 ) with an ED 50 of 32 nM, whereas the cis,cis-conformer (1a) is inactive. As a part of our program toward the total synthesis of marine natural products, 2 we have embarked on the total synthesis of ceratospongamide. 3Our retrosynthetic analysis of ceratospongamide is shown in Scheme 1. As the oxazoline ring is sensitive under acidic conditions, we used allo-L-threonine as a precursor of the oxazoline and postponed the cyclodehydration of the threonine residue to the final stage of the total synthesis for reducing the risk of racemization at the chiral center attached to the heterocycle. 4 For the synthesis of the macrocycle 2, a [5+2] convergent strategy was adopted to give the pentapeptide segment 3 and dipeptide segment 4. Because the thiazole and L-proline residues located on the Cterminus in peptide coupling would be tolerant of racemization, the segment condensation and macrocyclization at the thiazole/L-phenylalanine and L-proline/L-isoleucine amide bonds were chosen among the six amide bonds.For the preparation of the thiazole amino acid fragment 8, we applied our CMD (chemical manganese dioxide) oxidation for the conversion of thiazolidine to thiazole (Scheme 2).3b,5 Coupling of Boc-protected L-proline with N,O-dimethylhydroxylamine using DEPC (diethyl phosphorocyanidate) 6 afforded the amide 5 in 88% yield. After reduction of the amide 5 with lithium aluminum hydride, 7 the resulting aldehyde 6 was condensed with L-cysteine methyl ester to give the thiazolidine 7 as a diastereomeric N

show abstract

Synthesis of New Seven-Membered Ring Cyclic Dipeptides From Functionalized β-Amino Acids

Mahdi

Lavergne²,

Martínez

et al. 2000

Eur. J. Org. Chem.

View full text Add to dashboard Cite

A short synthesis of new, functionalized seven‐membered ring cyclic dipeptides is described. After the coupling of N‐protected β‐amino acids to N‐substituted α‐amino tert‐butyl esters, the protective groups of the terminal functions were removed and the cyclization took place diastereoselectively in the presence of the coupling agent BOP. Amide substitution was found to be effective in promoting the cyclization of linear dipeptides.

show abstract

Cyclization ofall-l-Pentapeptides by Means of 1-Hydroxy-7-azabenzotriazole-Derived Uronium and Phosphonium Reagents

Cited by 160 publications

References 30 publications

Synthesis of Cyclohexapeptides Containing Pro and Aib Residues.

Synthesis of Cyclohexapeptides Containing Pro and Aib Residues.

Total Synthesis of cis,cis-Ceratospongamide, a Bioactive Thiazole-Containing Cyclic Peptide from Marine Origin

Synthesis of New Seven-Membered Ring Cyclic Dipeptides From Functionalized β-Amino Acids

Contact Info

Product

Resources

About