Effect of copper(II) chloride on suppression of racemization in peptide synthesis by the mixed anhydride and related methods.
In segment couplings by the mixed anhydride method using isobutyloxycarbonyl chloride, the use of copper(II) chloride as an additive suppressed racemization completely in the same manner as in the carbodiimide method reported previously. This was confirmed by employing a number of couplings between Z-dipeptides and amino acid esters. The racemization-suppressing effect of other compounds were also evaluated by employing one of these model couplings to be at best only limitedly effective. Copper(II) chloride was effective also in the related method using EEDQ. Thus, in the couplings where a low level of racemization was observed without an additive, the addition of copper(II) chloride eliminated racemization even at ambient temperature where EEDQ is usually used. The effectiveness of copper(II) chloride was confirmed also in the BOP-Cl method. In the presence of HOBt racemization was reduced to a low but still detectable level, while it was suppressed completely by the addition of copper(II) chloride.
Miyazawa
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T
Department of Chemistry, Faculty of Science, Konan University, Kobe, Japan.
Donkai
T
T
Yamada
T
T
Kuwata
S
S
D002245:Carbon Dioxide / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis*; D011804:Quinolines / Q000737:chemistry; D013237:Stereoisomerism
D009943:Organophosphorus Compounds; D010080:Oxazoles; D010455:Peptides; D011804:Quinolines; D002245:Carbon Dioxide; C000470:EEDQ; C078142:bis(2-oxo-3-oxazolidinyl)phosphinic chloride; D003300:Copper; C029892:cupric chloride