APPLICATION OF 4 NOVEL ORGANOPHOSPHORUS C OMPOUNDS AS COUPLING REAGENTS FOR SYNTHESIS OF BIOACTIVE PEPTIDES

Four novel organophosphorus compounds: N-diethylphosphoryl benzoxazolo ne (DEPBO), N-(2-oxo-1,3,2-dioxaphosphorinanyl)-benzoxazolone (DOPBO), 3-[O-(2-oxo-1,3, aphosphorinanyl)-oxy]-1,2,3-benzotriazin-4(3H)-one ( DEPBT) and 3-(diethylphosphoryl-oxo)-1 ,2,3-benzotriazine-4 (3H)-one ( DEPBT) have been studied for peptide synthesis. All of the four compou nds are stable colourless crystal which can be easily prepared in larg e quantity, We have synthesized a number of bioactive peptides such as analogues of delta sleep inducing peptide, a cyclic heptapeptide isol ated form Caryophyllaceae, etc, by using these organophosphorus compou nds as coupling reagents in both solution and solid phase peptide synt hesis, In the coupling reaction, the hydroxy group in amino component does not need to be protected and the dehydration of asparagine which is easily caused by DCC or EDC was not observed, We have also compared our organophosphorus compounds with other coupling reagents such as D CC/HOBt, BOP, etc, In terms of reaction yield, our compounds are as go od as other commonly used coupling reagents, Among the four compounds, DEPBT gives the best results, As far as the racemization is concerned , especially in the hindered coupling or in the cyclization, DEPBT is much better than the others.