Tris-(hydroxymethyl)-aminomethane Derivatives. IV. Substituted 4-Hydroxymethyloxazolidines; Ester and Amide Interchange<sup>1</sup>

Pierce, J. Stanton; Lunsford, Carl D.

doi:10.1021/ja01150a050

Cited by 17 publications

(4 citation statements)

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“…Hydrolysis of the oxazoline contributes to a release in steric strain in the cyclic ring, although the major planarity imposed by the conjugation of the thiazole rings and associated amides, as observed in ascidiacyclamide itself, is retained. ,,, The hydrolysis of an oxazoline ring could lead to two products. Acid-induced hydrolysis involves nucleophilic addition of water across the oxazoline double bond to form an amino lactone; subsequent addition of base causes nucleophilic addition−elimination to the threonine-containing product (Scheme ) . The amino lactone only has been isolated in this work.…”

Section: Resultsmentioning

confidence: 99%

A Novel Potassium-Binding Hydrolysis Product of Ascidiacyclamide: A Cyclic Octapeptide Isolated from the Ascidian Lissoclinum patella

et al. 1996

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A new octapeptide has been isolated and characterized as its potassium complex from acidic aqueous methanol solutions of ascidiacyclamide, a cyclic peptide isolated from the ascidian Lissoclinum patella. Crystals suitable for X-ray structure determination were orthorhombic, space group P2(1)2(1)2(1), with a = 15.442(3) Å, b = 36.167(1) Å, c = 9.567(3) Å, V = 5343(2) Å(3), Z = 4, and R = 0.069. The structure consists of the macrocyclic cation, three perchlorate anions, and two water molecules. The macrocyclic ring of ascidiacyclamide remains intact, but two oxazoline rings have been opened to form two amino lactones, with the amine protonated. A potassium ion is bound to the N atoms of the thiazole rings (K(1).N(1), 2.47(2) Å; K(1).N(5), 2.50(2) Å) and to the adjacent O (amide) atoms (K(1).O(1), 2.34(1) Å; K(1).O(5), 2.34(1) Å). Two perchlorate anions, located on either side of the plane of the macrocyclic ring, are weakly associated with the potassium cation (K(1).O(10), 2.72(3) Å; K(1).O(16), 2.48(3) Å). This cyclic octapeptide reacts with copper(II) to give a purple solution (lambda(max) 590 nm).

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Section: Resultsmentioning

confidence: 99%

A Novel Potassium-Binding Hydrolysis Product of Ascidiacyclamide: A Cyclic Octapeptide Isolated from the Ascidian Lissoclinum patella

et al. 1996

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“…The reaction of carbonyl compounds with Cys has been extensively studied (22,23 (24,25) and is a dominating side reaction formed through an intramolecular 0-to-N acyl transfer reamc (26) in the acidic deprotection step of peptide synthesis tion ( Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

Peptide segment ligation strategy without use of protecting groups.

Liu

Tam

1994

Proc. Natl. Acad. Sci. U.S.A.

210

161

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We describe the concept and the verification of a chemical ligation approach to the synthesis of proteins using peptide se-ents with no protecting groups and no activation of the C-tenal a-carboxyl group. This approach of three steps: (i) aldehyde introduction, in which a masked glycolaldehyde ester Is linked to the carboxyl terminus of an unprotected peptide by reverse protedlysis; (ii) ring formation, in which the umaked aldehyde reacts with the N-teinal a-amino group of the second unprotected peptide containing either a cysteine or a threonine residue to form a t ne or olidine ring at an acidic pH; and (iii) rearrangement in which O-acyl ester linkage is transferred to N-acyl amide linkage to form a peptide bond with a pseudoproline stuture at higher pH. The (4), and the semi-synthesis of proteins consisting of components from synthetic peptides with unusual amino acids and proteins obtained through recombinant technology.The conventional segment-synthesis approaches (5) usually require a maximal protection strategy which has the limitations ofpoor solubility, low coupling efficiency, and the possible danger of racemization due to the overactivation of the carboxyl group. Considerable efforts have been made to overcome these limitations through the use of partial or minimal protecting-group strategies and improvements in the activation methods (6-11). However, these approaches do not overcome the problem of the poor coupling efficiency between large peptide segments, because of the intrinsic difficulty of obtaining effective molar concentrations for high molecular weight molecules. Alternative approaches to overcome the difficulty of forming amide bonds use hydrazone (12,13) or thioether and thioester (14) as surrogate bonds. The advantage of these peptide-bond replacement approaches resides in the high and specific reactivity between the two functional groups not found in amino acids to make the conjugation efficient. The disadvantage is that these linkages are substantially different from the peptide bond, which may lead to conformational distortion, and are usually not stable at either acidic (12) or basic (14) pH.We have now designed and developed a chemical ligation method by which two unprotected peptide segments can be ligated together through an amide bond. In our design, we make use of a highly regiospecific and efficient reaction to link covalently two unprotected peptides. The selectivity of this reaction would also obviate the need for any protecting groups. A peptide bond is then formed in a second step through an intramolecular rearrangement between the two closely neighboring carboxyl and amino groups. The efficiency of the first reaction would solve the slow kinetic problem for reactions between large molecules, and the second reaction, designed as a spontaneous process to form amide bonds without activating the carboxyl group, would overcome the racemization problem of the conventional segment condensation method. EXPERIMENTAL PROCEDURESGeneral. 1H NMR spectra were obtained at 300 ...

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“…On substances of the last type (with various acyl groups), the stepwise hydrolysis of the ring system has been studied (91). Hydrochloric acid gives one molecule of benzaldehyde and the hydrochloride of the oxazolidine: These reactions are of some importance in connection with the general study of the acylation of oxazolidines (see page 321).…”

Section: Chrmentioning

confidence: 99%

The Oxazolidines.

Bergmann¹

1953

Chem. Rev.

178

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Tris-(hydroxymethyl)-aminomethane Derivatives. IV. Substituted 4-Hydroxymethyloxazolidines; Ester and Amide Interchange¹

Cited by 17 publications

References 0 publications

A Novel Potassium-Binding Hydrolysis Product of Ascidiacyclamide: A Cyclic Octapeptide Isolated from the Ascidian Lissoclinum patella

A Novel Potassium-Binding Hydrolysis Product of Ascidiacyclamide: A Cyclic Octapeptide Isolated from the Ascidian Lissoclinum patella

Peptide segment ligation strategy without use of protecting groups.

The Oxazolidines.

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Tris-(hydroxymethyl)-aminomethane Derivatives. IV. Substituted 4-Hydroxymethyloxazolidines; Ester and Amide Interchange1

Cited by 17 publications

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A Novel Potassium-Binding Hydrolysis Product of Ascidiacyclamide: A Cyclic Octapeptide Isolated from the Ascidian Lissoclinum patella

A Novel Potassium-Binding Hydrolysis Product of Ascidiacyclamide: A Cyclic Octapeptide Isolated from the Ascidian Lissoclinum patella

Peptide segment ligation strategy without use of protecting groups.

The Oxazolidines.

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Tris-(hydroxymethyl)-aminomethane Derivatives. IV. Substituted 4-Hydroxymethyloxazolidines; Ester and Amide Interchange¹