Significant development and scale-up work was completed on the synthesis of an antibody drug conjugate payload based on the tubulysin natural products. This work included the development of new routes to the tubuvaline and tubuphenylaniline portions of the molecules, as well as extensive optimization of the solid phase peptide synthesis used to assemble the molecule. The initial route (21 steps longest linear sequence, 0.01% overall yield) was improved to a new, more robust route (19 steps longest linear sequence, 2.4% overall yield) affording a 240-fold increase in overall yield and allowing delivery of over 86 g of the required molecule.

中文翻译：

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抗体药物结合物Tubulysin有效载荷的开发和规模化

在基于微管溶素天然产物的抗体药物偶联物有效载荷的合成上，完成了重要的开发和扩大规模的工作。这项工作包括开发通往分子的tubuvaline和tubuphenylaniline部分的新途径，以及对用于组装分子的固相肽合成的广泛优化。初始路线（最长21步线性序列，总产率为0.01％）改进为新的，更稳健的路线（最长19步线性序列，总产率为2.4％），使总产量增加了240倍，并且可以运送超过86 g所需的分子。