PyBOP reagent

Champagne, J.-M., Coste, J., and Jouin, P. (1993) Synthesis of mixed phosphonate diester analogues of dipeptides using BOP or PyBOP reagents. Tetrahedron Lett. 

Fig. 32 Fluorous mixture synthesis of fused-tricyclic hydantoins. Reagents and conditions a Mo(CO)6, DMSO, toluene, MW 150 °C, 35 min, closed system b TFA CH2CI2 (1 1), rt c PhC2H4NH2, PyBOP, i-Pr2EtN, MeOH, CH2CI2 followed by flash chromatography and F-HPLC d i-Pr2EtN, MeOH, MW 140 °C, 40 min, followed by F-SPE...

FIGURE 2.19 Pyrrolidino instead of dimethylamino substitutents for the environmental acceptability of phosphonium and carbenium salt-based reagents.56 Tetramethylurea from O-benzotriazol- l -yl/V./V./V./V -tetramethyluronium hexafluorophosphate and tetrafluoroborate is more volatile and is cytotoxic. The product released from PyBOP is not environmentally objectionable. PyBOP = benzotriazol-l-yl-oxytripyrrolidinophosphonium hexafluorophosphate. 

J Coste, D Le-Nguyen, B Castro. PyBOP A new peptide coupling reagent devoid of toxic by-product. Tetrahedron Lett 31, 205, 1990. 

BOP, PyBOP, HBTU, HATU, and so forth with an additive It has been considered essential to use an additive with these reagents because the tertiary amine required to effect the coupling promotes isomerization. Diisopropylethylamine or possibly trimethylpyridine are the bases of choice to minimize the side reaction, but the additive may increase isomerization (see Section 7.18). 

Use an onium salt-based reagent such as PyBOP, T/HBTU (see Sections 2.18-2.21), PyAOP (see Section 7.19), or other with me corresponding additive and diisopropylethylamine or trimethylpyridine as tertiary amine without an excess. The additive may, however, promote epimerization. 

The incorporation of Fmoc-Phe[CF2PO(OEt)2]-OH in Fmoc-based solid-phase synthesis is readily performed using DIC/HOBt, PyBOP, and other uronium-based reagents (HBTU, HATU). The deprotection of the peptide-resin is effected by the one-step treatment of the... 

In addition to the conversion into phosphonochloridates as described in Section 10.10.2.1.2, phosphonate monoacids can also be activated for coupling via some of the popular reagents from standard peptide chemistry, such as BroP, 77 BOP/ and PyBOP. 79 One-pot activation and coupling of hydrogen phosphinates with a-hydroxy acids is also possible via the method outlined in Section 10.10.2.1.3. 76 The procedure outlined in Scheme 19 illustrates an optimized procedure for coupling a hindered phosphonate 57 and an a-hydroxy acid derivative via the phosphonochloridate 72 ... 

A selection of commercially available phosphonium salts suitable for the activation of carboxylic acids in the presence of amines is sketched in Figure 13.5. Phosphonium salts such as those shown in Figure 13.5 do not react with amines, and are well suited for preparing amides on insoluble supports, with either the amine or the acid linked to the support (Table 13.5). Solutions of these reagents in dry DMF are quite stable and can be used even after standing at room temperature for several days [84]. BOP, one of the first phosphonium salts used for peptide synthesis [85], leads to the formation of mutagenic HMPA, and should therefore be replaced by the less hazardous PyBOP [86],... 

Reagents. Reagents for peptide synthesis are Va-Fmoc-Lys(Dde)-OH and /Va -Boc-Glu(ODmab)-OH, acetic anhydride, PyBOP, DIEA, l-hydroxy-7-azabenzotriazole (HOAt), and 2% hydrazine/DMF. 

Peptide synthesis reagents such as diisopropylcarbodiimide (DIC), benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP), 2-(lH-benzotriazole-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (HBTU), 1-hydroxybenzotriazole (FlOBt), piperidine, A-methylmorpholine (NMM), trifluoroacetic acid (TEA), triisopropylsilane (TIS), A -diisopropylethylamine (DIPEA, DIEA), l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,2-ethanedithiol (EDT), and 4-dimethylaminopyridine (DMAP) may be obtained from Sigma-Aldrich, Chemlmpex, and Novabiochem. 

Scheme 4.1 Synthesis of oligopeptide conjugates. Reaction conditions and reagents (a) n-BuLi, THF, -78°C->0°C 1(3-bromopropyl)-2,2,5,5-tetramethyl-l,l-aza-2,5-disilacyclopentane THF/HCl (b) Fl2 (lOObar), Pd/C, toluene, 80°C, 3 days (c) Fmoc-Ala-OH, EDCI/HOBt, TEA, DCM, -40°C r.t. (d) piperidine, chloroform (e) Fmoc-Ala-Ala-OH, PyBOP, DIEA, DCM, r.t.

New thioacylating reagents were developed. A combination of monothio-carboxylic acids with a PyBOP type reagent, containing phosphorus with a potential P=0 bond formation as the driving force [50, 51], works efficiently. A thionoacid derivative of nitrobenzotriazole provided a mild and race-misation free coupling with phenylalanine methyl ester [52]. This shows that this route is not a dead end as had been feared for some time [53]. 

First, the (/f)-2-methylcysteine compound 5 is N- and S-protected and coupled with the threonine methyl ester to the hydroxyamide 57 with benzotriazole-1 -yloxy-tripyrrolidino-phos-phonium hexafluorophosphate (pyBOP) [16]. Burgess reagent [17] turns out to be the best choice for the conversion of 57 into 58. The use of Burgess reagent for the synthesis of oxazo-line was examined extensively by Wipf et al. [ 18]. For other methods of synthesizing oxazoles, which were developed in connection to the synthesis of calyculin A, see [19]. 

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