Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1993-9-10
|
| pubmed:abstractText |
N-tert-Butoxycarbonylamino acids (Boc-Xaa-OH) were coupled with p-nitrophenol (HONp) in dichloromethane using N,N'-dicyclohexylcarbodiimide (DCC) and N-ethyl-N'(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), and the products were identified and quantitated by high-performance liquid chromatography. Boc-Xaa-OH with Xaa = Val was coupled also with pentafluorophenol (HOPf) and hydroxy-containing additives (HOR), and the products were similarly determined as the methylamides. EDC-mediated reactions of Boc-Xaa-OH gave 8-25% of Boc-Xaa-Xaa-OR as well as Boc-Xaa-OR for R = Ph, Np, Pf, benzotriazole (Bt) and 5-norbornene-endo-2,3-dicarboxamide; DCC-mediated couplings, 5-7% for R = Np and Bt. No dimer was formed in couplings with N-hydroxysuccinimide or 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine. Dimerization was eliminated from DCC-mediated reactions by the addition of 1 equiv. of N-methylmorpholine, from the EDC-mediated reactions by carrying them out in pyridine. Dimerization is attributed to formation of the intermediate 2-alkoxy-5(4H)-oxazolone that undergoes fragmentation to the N-carboxyanhydride, which reacts with the alcohol giving amino acid ester. Ester produces dimer by aminolysis of the O-acylisourea. Decomposition (1.4%) was also detected by analysis for H-Val-Phe-OMe in DCC-mediated reactions of Boc-valine with H-Phe-OMe, and was demonstrated to be caused by the hydrochloride of the ester salt that had been neutralized with N-methylmorpholine. Decomposition was eliminated by the addition of 5% of pyridine, which also had the beneficial effect of suppressing N-acylurea formation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-nitrophenol,
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Dicyclohexylcarbodiimide,
http://linkedlifedata.com/resource/pubmed/chemical/Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Formic Acid Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrochloric Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Methylene Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrophenols,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/pyridine,
http://linkedlifedata.com/resource/pubmed/chemical/t-butyloxycarbonyl group
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0367-8377
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
41
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
587-94
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8349416-Amino Acids,
pubmed-meshheading:8349416-Dicyclohexylcarbodiimide,
pubmed-meshheading:8349416-Esters,
pubmed-meshheading:8349416-Formic Acid Esters,
pubmed-meshheading:8349416-Hydrochloric Acid,
pubmed-meshheading:8349416-Hydroxylamines,
pubmed-meshheading:8349416-Methylene Chloride,
pubmed-meshheading:8349416-Models, Chemical,
pubmed-meshheading:8349416-Nitrophenols,
pubmed-meshheading:8349416-Peptides,
pubmed-meshheading:8349416-Pyridines
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Identification and suppression of decomposition during carbodiimide-mediated reactions of Boc-amino acids with phenols, hydroxylamines and amino acid ester hydrochlorides.
|
| pubmed:affiliation |
Department of Biochemistry, University of Ottawa, Ontario, Canada.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|