4个新型有机磷缩合试剂的合成及其在生物活性肽合成中的应用

报道了4个新型有机磷化合物：N-二乙氧基磷酰苯并唑酮(DEPBO)、N－(2-氧-1,3,2-二氧杂磷杂环乙烷基)-苯并唑酮(DOPBO)、3－(2'-氧-1',3',2'-二氧杂磷杂环己烷基)-氧-1,2,3-苯共三嗪-4(3H)-酮(DOPBT)和3－(二乙氧基磷酰基)-氧-1,2,3-苯并三嗪-4(3H)-酮(DEPBT)的合成,并研究了它们作为缩会试剂在多肽合成中的应用. 研究结果表明,它们可以成功地用于固相法和溶液法合成多肽,其中DEPBT还可用于环肽的合成. 应用DEPBO和DEPBT合成了促睡眠肽的类似物及从云南中草药繁缕中分离鉴定的一个环七肽等生物活性肽.

Application of Four Novel Organophosphorus Compounds as Coupling Reagents for Synthesis of Bioactive Peptides

Four novel organophosphorus compounds: N-diethylphosphoryl benzoxazolone(DEPBO), N- (2-oxo-1, 3, 2-dioxaphosphorinanyl)-benzoxazolone (DOPBO), 3- O- (2-oxo-1, 3, 2-dioxaphosphorinanyl)-oxy]-1, 2, 3-benzotriazin-4 (3H)-one (DOPBT) and 3-(di-ethylphosphoryl-oxo) -1, 2, 3-benzotriazine-4 (3H)-one (DEPBT) have been studied for pep-tide synthesis. All of the four compounds are stable colourless crystal which can be easilyprepared in large quantity. We have synthesized a number of bioactive peptides such as ana-logues of delta sleep inducing peptide, a cyclic heptapeptlde isolated form Caryophyllaceae,etc. by using these organophosphorus compounds as coupling reagents in both solution andsolid phase peptide synthesis. In the coupling reaction, the hydroxy group in amino compo-nent does not need to be protected and the dehydration of asparagine which is easily causedby DCC or EDC was not observed. We have also compared our organophosphorus com-pounds with other coupling reagents such as DCC/HOBt, BOP, etc. In terms of reactionyield, our compounds are as good as other commonly used coupling reagents. Among thefour compounds, DEPBT gives the best results. As far as the racemization is concerned, es-pecially in the hindered coupling or in the cyclization, DEPBT is much better than the oth-ers.