Bop‐Cl mediated cyclization of a linear precursor of virginiamycin S. Contra indication for using HOBt as racemization suppressor

Cyclization of a model linear hexapeptide (VS 1 , linear peptide, 1) was achieved at moderate temperature (‐15° to r. t.) in ≥80% yields in using BOP‐C1 [N, N'‐bis(2‐oxo‐3‐oxazolidinyl) phosphinic chloride] and BOP‐reagent [benzotriazolyloxy tris (dimethylamino) phosphonium hexafluorophosphate] as coupling reagents in one‐pot procedures. Stereomutation was high (∼︁40%). The addition of N‐hydroxybenzotriazole doubled the degree of epimerization. A rationale is offered in order to explain the enantiomeric induction. High dilution was necessary to avoid side products (dimer/trimer) formation. However, dilution does not effect the rate of cyclization considerably.