The cryptophycins are a unique family of 16-membered macrolide antimitotic agents isolated from the cyanobacteria Nostoc sp. Their molecular target is tubulin protein wherein they are the most potent known stabilizers of microtubule dynamics and depolymerize microtubules at higher concentrations. They also deactivate the Bcl2 protein and produce apoptotic response much more quickly and at considerably lower concentrations than clinically utilized compounds. The presence of several amide and ester linkages within the cryptophycin core provides access to very convergent total synthetic approaches. Likewise, the modularity of the structure renders their synthesis amenable to structure-activity studies in several regions of the molecule. The in vivo hydrolytic instability of the C5 ester was a key obstacle to the successful identification of a clinical candidate. This problem was ameliorated by increased substitution at C6 as in the presence of gem-dimethyl substitution in the clinical candidate, cryptophycin-52.

中文翻译：

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隐藻素：它们的合成和抗癌活性。

隐藻素是从蓝细菌Nostoc sp中分离的独特的16元大环内酯类抗有丝分裂剂家族。它们的分子靶标是微管蛋白，其中微管蛋白是已知的最有效的微管动力学稳定剂，并在较高浓度下使微管解聚。与临床上使用的化合物相比，它们还使Bcl2蛋白失活并以更快的速度和更低的浓度产生凋亡反应。隐藻素核心中存在几个酰胺键和酯键，提供了非常收敛的总合成方法。同样，结构的模块性使其合成适合在分子的几个区域进行结构活性研究。C5酯的体内水解不稳定性是成功鉴定临床候选药物的关键障碍。通过在临床候选者隐藻霉素-52中存在宝石-二甲基取代的情况下，通过在C6处增加取代来改善该问题。