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Patent CN113801233A discloses coupling Boc-modified semaglutide propeptide with Fmoc compound (such as Fmoc-His-Aib or Fmoc-His-Aib-Glu), removing Boc-linked tertiary butyl protected side chain, removing Fmoc, and removing tertiary butyl to obtain semaglutide, which has many steps, and requires frequent deprotection (3 times of deprotection) to cause racemization of some amino acids, especially racemization of terminal His and introduction of other impurities with incomplete Fmoc removal, thereby causing great difficulty in subsequent purification
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The funnel plot displayed a symmetrical distribution, suggesting no publication bias, supported by Beggs test (p = 0.73), although Eggers test indicated a significant small study effect (p = 0.002)
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