The diversification of late stage synthetic intermediates provides significant advantages in efficiency in comparison to conventional linear approaches. Despite these advantages, accessing varying ring scaffolds and functional group patterns from a common intermediate poses considerable challenges using existing methods. The combination of regiodivergent nickel-catalyzed C–C couplings and site-selective biocatalytic C–H oxidations using the cytochrome P450 enzyme PikC addresses this problem by enabling a single late-stage linear intermediate to be converted to macrolactones of differing ring size and with diverse patterns of oxidation. The approach is made possible by a novel strategy for site-selective biocatalytic oxidation using a single biocatalyst, with site selectivity being governed by a temporarily installed directing group. Site selectivities of C–H oxidation by this directed approach can overcome positional bias due to C–H bond strength, acidity, inductive influences, steric accessibility, or immediate proximity to the directing group, thus providing complementarity to existing approaches.

中文翻译：

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使用单一生物催化剂从常见线性底物合成多种 11 元和 12 元大环内酯

与传统的线性方法相比，后期合成中间体的多样化在效率方面提供了显着的优势。尽管有这些优点，但使用现有方法从通用中间体获取不同的环支架和官能团模式仍面临相当大的挑战。区域发散的镍催化 C-C 偶联和使用细胞色素 P450 酶 PikC 的位点选择性生物催化 C-H 氧化的组合解决了这个问题，使单个后期线性中间体能够转化为不同环大小和不同结构的大内酯。氧化模式。该方法是通过使用单一生物催化剂进行位点选择性生物催化氧化的新策略而实现的，其中位点选择性由临时安装的导向基团控制。这种定向方法的 C-H 氧化位点选择性可以克服由于 C-H 键强度、酸性、诱导影响、空间可及性或直接接近定向基团而导致的位置偏差，从而为现有方法提供补充。