BOP reagent

Benzotriazol-l-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent)... 

D Le-Nguyen, A Heitz, B Castro. Renin substrates. Part 2. Rapid solid phase synthesis of the ratine sequence tetradecapeptide using BOP reagent. J Chem Soc Perkin Trans 1 1915, 1987. 

B Castro, J-R Dormoy, G Evin, C Selve. Peptide coupling reagents. Part VII. Mechanism of the formation of active esters of hydroxybenzotriazole in the reaction of carboxylate ions on the BOP reagent for peptide coupling. A comparison with Itoh s reagent. J Chem Res (S) 82, 1977. 

BOP reagent benzotriazol-l-yloxytris(dimethyIamino)phosphonium hexafluorophosphate... 

The side-chain protected peptide was first synthesized on 4-nitrobenzophenone oxime resin utilizing Boc chemistry (see Section 12.4.1.2). Briefly, the first amino acid residue was attached to the resin using DIC activation. Subsequent couplings of residues to the resin-bound peptide were accomplished employing the BOP reagent for carboxy activation of the a-amino acids avoiding preneutralization of the resin-bound peptides for reasons discussed above. A six-fold excess of amino acid is utilized for the third... 

The synthesis of (-t-)-polyoxin J 14 is completed by selective ester hydrolysis with aqueous lithium hydroxide. The resulting carbamoylpolyoxamic acid was then coupled with the protected thymine polyoxin C 8 with the BOP reagent (Castro s reagent)14 (benzotriazol-1 -yloxytris(dimethyl-amino)phosphonium hexafluoro-phosphate) 37 to furnish the peptide derivative in 63 % yield. 

The stereoselective synthesis of (+)-polyoxin J is accomplished by Gosh in 24 steps and 3 % overall yield. The key intermediates are protected thymine polyoxin C 8 and the 5-Ocarbamoyl polyoxamic acid 2, which were synthesized from D-ribose and dimethyl L-tartrate. Key steps are two different epoxidation reactions, one carried out with MCPBA and the other under Sharpless conditions with the D-(-)-tartrate. Both epoxides are opened with diisopropoxytitanium diazide. The coupling of the two fragments was realized with the BOP reagent 37. This synthesis provides an easy access to the synthesis of various (+)-polyoxin J analogs for biological evaluation. 

This reagent, benzotriazol-l-yl-oxytripyrrolidinophosphonium hexafluorophosphate (14, PyBOP)P l (Scheme 4), was designed in order to avoid the formation of toxic HMPA during acylation. As with BOP, it is assumed that the first step is the carboxylic acid activation which involves formation of an acyloxyphosphonium salt.P This initial salt is then attacked by the benzotriazolyloxy anion to form the benzotriazolyl active ester which then reacts with the amino component. PyBOP can easily replace the BOP reagent and is especially suitable for solid-phase peptide synthesis. It is soluble in a wide range of solvents such as DMF, di-chloromethane, THF, and NMP. PyBOP is more useful in peptide synthesis on solid support than in solution. The byproduct, tris(pyrrolidino)phosphine oxide is partially water-soluble and is easily removed by washing. PyBOP is used under the same experimental conditions as BOP. Note that PyBOP is a white, crystalline and non-hygroscopic solid. It can be kept as a solid, but solutions of PyBOP cannot be stored for more than 24 hours. 

Treatment of the hexamethylphosphoric triamide, hexamethylphosphoramide, (MejN)jPO, with COClj gives [(MejN)3POCOCl]Ci, which decarboxylates to [(Me2N)3PCl]Cl - an intermediate in the preparation of the peptide coupling reagent known as the BOP reagent [341,342,778],... 

A novel (and cheaper) method for the preparation of the peptide-coupling reagent benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate (i.e. BOP reagent) has been described. ... 

The final fragment assembly is shown in Scheme 1.324. Coupling 1265 with 1267 was accomplished with BOP reagent" to afford 1268. The THP group was... 

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