A kind of solid phase synthesis process of Lanreotide

A kind of solid phase synthesis process of Lanreotide

  • CN 108,059,667 B
  • Filed: 02/10/2018
  • Issued: 11/13/2018
  • Est. Priority Date: 02/10/2018
  • Status: Active Grant
First Claim
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1. a kind of solid phase synthesis process of Lanreotide, which is characterized in that including steps are as follows:

  • 1) condensation reaction:

    In condensation system, using Fmoc amino resins as the carrier of synthesis in solid state, resin is through being swollen, sloughingAfter Fmoc protecting groups and washing, from C-terminal to N-terminal, condensation connects 8 Fmoc- ammonia activated, containing Side chain protective group successivelyBase acid, obtains linear peptide resin Fmoc-D-2-Nal-Cys (the Trt)-Tyr (tBu)-of full guard that N-terminal amino contains Fmoc protecting groupsD-Trp(Boc)-Lys (Boc)-Val-Cys (Trt)-Thr (OtBu)-amino resins;

    It is described be condensed successively protected amino acid sequence be:

    Fmoc-Thr(OtBu)-OH、

    Fmoc-Cys(Trt)-OH、

    Fmoc-Val-OH、

    Fmoc-Lys(Boc)-OH、

    Fmoc-D-Trp(Boc)-OH、

    Fmoc-Tyr(tBu)-OH、

    Fmoc-Cys(Trt)-OH,Fmoc-D-2-Nal-OH;

    The condensation system is:

    A+D or A+B+C, wherein A be HOBT or HOAT, B HATU,HBTU, TBTU or PyBOP any of which, C are DIEA or TMP, D DIC;

    2) I is added2Content is Isosorbide-5-Nitrae-dioxane solution of 8 eq, 1~5 h is reacted under the conditions of 10~30 DEG C, to step

         1)After the linear peptide resin of full guard obtained is cyclized, resin is washed with carbon tetrachloride and DMF respectively, obtains cyclic peptide resin;

    3) the Fmoc protecting groups on cyclic peptide resin N-terminal D-2-Nal amino made from step

         2) are removed, the exposed ring of N-terminal amino is obtainedPeptide resin;

    4) Side chain protective group of the exposed cyclic peptide resin of N-terminal amino made from step

         3), and cutting resin are removed, it is thick to obtain LanreotidePeptide;

    5) the thick peptide of Lanreotide made from step

         4) purified, be lyophilized, obtain Lanreotide sterling.

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