布舍瑞林的合成

Synthesis of buserelin

目的:探索布舍瑞林的合成方法。方法:先采用Fmoc固相多肽合成法,以2-CTC(2-chlorotrityl chloride)树脂做载体,DIC/HOBT做缩合剂,逐步缩合得到全保护布舍瑞林肽树脂,以2%TFA/DCM切割树脂,然后在PyBOP催化下接乙胺基,再用钯碳和甲酸铵催化氢化脱除硝基和苄基,最后用15%TFA/DCM选择性脱去三苯甲基保护基得粗肽,半制备反相高效液相色谱法纯化。结果:布舍瑞林粗品纯度达80%,粗品经半制备反相高效液相色谱纯化,所得精肽纯度大于98%,总收率为30%。结论:该方法工艺简单,产品成本低,纯度高,可为工业化生产提供借鉴。

Objective： To develop a method for synthesis of buserelin. Methods： Buserelin was synthesized by Fmoc solid phase peptide synthesis method using 2-CTC （2-chlorotrityl chloride） resin as a solid carrier and DIC/HOBT as condensing agents. The protected peptide was obtained by cleavage with 2% TFA/DCM and coupled with ethylamine by using PyBOP as a coulpling reagent, and the crude peptide was obtained following the hydrogenation and selective deprotection of Trt. The pure buserelin was obtained after purification on semi-preparative RP-HPLC. Results： The purity of the crude peptide was more than 80%. After the purification by semi-preparative RP-HPLC, the purity was more than 98% , and the overall yield was 30%. Conclusion： The method is simple and cost-effective, and can produce buserelin with high purity, which may be useful for the industrial production.