HOBt as coupling reagent

Method B Alternatively, the branched peptide-resin was synthesized using HBTU/HOBt as coupling reagents. The above mentioned Fmoc amino acids (1.95 mmol) were coupled to Fmoc-Gly-SASRIN-resin (lg, sub. level =0.65 mmol-g1) with HOBt (0.26g, 1.95mmol), HBTU (0.67g, 1.76mmol), and DIPEA (0.63 mL, 3.71 mmol) in DMF without preactivation. The coupling was complete within 1 to 2 h. 

Other coupling reagents, such as HBTU or HATU, are also effective in place of BOP/HOBt as described. 

The incorporation of derivatives Fmoc-Ser[PO(OBzl)(OH)]-OH (18) and Fmoc-Thr[PO(OBzl)(OH)]-OH is best effected using uronium reagents such as HBTU/HOBt/ DIPEA and HATU/HOAt/DIPEA since both BOP and PyBroP failed to effect complete incorporation in comparative test couplings. 48 In a separate work, the BOP/HOBt/DIPEA coupling of Fmoc-Ser[PO(OBzl)(OH)]-OH was found to be only 85% complete after double coupling and the incorporation of the anionic phosphorodiester caused a decrease in the coupling efficiency of following residues. 94 Despite these potential problems, both Fmoc-Ser[PO(OBzl)(ONa)]-OH and Fmoc-Thr[PO(OBzl)(ONa)]-OH have been successfully employed for the Fmoc-based solid-phase synthesis of various Ser(P)- and Thr(P)-... 

DIC-derived A-acylurea were obtained. Additives such as HOBt or DMAP, or other coupling reagents (EDC, HATU, DECP) did not lead to cyclization in this case [434]. 

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