Uronium salts

Acid B.P. H.P. AnlUde p-Tolu4- dide 1 Amide p-Bromo- phenacyl ter p-Nitro- benzyl Ester p-Phenyl phenacyl Ester S-Benzyl- uo-thi- uronium Salt Other Derivatives... 

Acid Sulphon- amide ArSO,NH, S-Benzyl- Ao-thl- uronium Salt SulphoD- aniUde ArSO,NHPh />-Tolul- dine Salt Sulphonyl Chloride, ArSO,Cl... 

HYDROXYBENZOTRIAZOLE AS ADDITIVE IN COUPLINGS OF N-ALKOXYCARBONYLAMINO ACIDS EFFECTED BY PHOSPHONIUM AND URONIUM SALT-BASED REAGENTS... 

Phosphonium and uronium salt-based reagents effect couplings by first reacting with the anion of the starting acid (Figure 2.22, path A). The benzotriazolyl ester is then one of the two possible precursors of the peptide. Operating in a research climate in which HOBt was commonly used as additive, Hudson rationalized that if the ester is the precursor of the peptide, additional HOBt in the form of the anion would be beneficial because it would by mass action promote formation of the ester. A favorable effect from adding HOBt was reported, so one variant of the use of... 

FIGURE 2.22 Couplings using phosphonium and uronium salt-based reagents with 1-hydroxybenzotriazole as additive.60 The additional HOBt promotes formation of the benzotriazolyl ester, which is the precursor of the peptide. 

Phosphonium and uronium salts (see Sections 2.17-2.19) These are rarely used alone because of isomerization that is promoted by the tertiary amine that is required to effect the reaction. 

When HOBt and HOAt are used with phosphonium and uronium salt-based reagents, they are present as anions, and they suppress epimerization by trapping the O-acyloxyphosphonium, O-acy I uronium, and oxazolone intermediates as the activated esters (see Section 2.21). 

Phosphonium or uronium salts added to the two reacting species followed by the tertiary amine. The protected amino acid must be added before the reagent otherwise, the latter will react with the amino groups. Bond formation is rapid,... 

LA Carpino, H Imazumi, A El-Faham, FJ Ferrer, C Zhang, Y Lee, BM Foxman, P Henklein, C Hanay, C Miigge, H Wenschuh, J Klose, M Beyermann, M Bienert. The uronium/guanidinium peptide coupling reagents finally the true uronium salts. Angew Chem Inti Edn 41, 442, 2002. 

B pMeBHA (HF) dynorphin analogue HBTU, HATU, HAPyU, BOP, PyBOP, PyAOP Kaiser test phosphonium >>>uronium salts PyBOP>BOP [368]... 

Uronium salts can be used to convert carboxylates into HOBt or related esters [5], into pentafluorophenyl esters [95], or into acyl halides [10] in the presence of amines (Figure 13.6). A highly reactive O-acylisouronium salt is formed initially. This inter-... 

Figure 13.6. Activation of carboxylates by uronium salts [5,10,17,18,84,96], X leaving group. Table 13.6. Preparation of amides using uronium salts as coupling agents.

The reactivity of uronium- (and phosphonium-) based coupling reagents is mainly determined by the type of activated acid derivative formed during activation (see Figure 13.2). Unlike phosphonium salts, uronium salts can react with amines to yield guanidines [84]. This side reaction can interfere with amide formation if more uronium salt than carboxylic acid is used. Illustrative examples of the use of uronium salts are listed in Table 13.6. 

Acid Sulphonamide ArS02NH2 °C 5-Benzylisothio-uronium salt °C... 

Sulphonic acid B.P. °C Sulphonyl chloride, B.P. °C Sulphonamide, M.P. °C 5-Benzyl-isothio-uronium salt M.P. °C Sulphon- aniltde M.P. °C... 

A. Carpino, H. Imazumi, A. El-Faham, F. J. Ferrer, C. Zhang, Y. Lee, B. M. Foxman, P. Henklein, C. Hanay, C. Miigge, H. Wenschuh, The uronium/guanidinium peptide coupling reagents finally the true uronium salts. Angew. Chem. Int. Edn. 2002 41 442-445. 

For chain-elongation steps with Fmoc-Arg(Adoc)2-OH standard activation procedures are applied, such as active esters and the symmetric anhydride method, but even for the use of more powerful acylating agents, e.g. phosphonium and uronium salts, there are no contraindications. Final deprotection is performed using TFA under standard conditions of Fmoc/tBu chemistry. Properties similar to the Adoc group have been reported for iso-bornyloxycarbonyl protection, whereas increased acid lability is obtained with the 1-(1-adamantyl)- -methylethoxycarbonyl group. ... 

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