Macrolide biosynthetic P450 enzymes perform regio- and stereoselective oxidations of unactivated C-H bonds with ease, although the exploitation of this capability in organic synthesis remains underdeveloped. The PikC-catalyzed hydroxylation of YC-17 and narbomycin exemplifies such transformations, with oxidation occurring at positions distal from the desosamine directing group.  An engineered, self-sufficient PikC (PikCD50N-RhFRED) has been employed for the moderately regioselective hydroxylation of non-natural desosamine-linked carbocyclic rings, illustrating its potential as a biocatalyst for C-H oxidation.  Substrate scope has been extended to include macrocycles with non-sugar anchors, expanding the procedure's utility as a synthetic tool.  The selectivity of the oxidations was evaluated as a function of both the aglycone, employing unnatural substrates with variable degrees of structural complexity within the macrolactone ring, and the anchoring group, with non-sugar anchoring group analogs of both YC-17 and narbomycin.

Synthesis of unnatural substrates for PikC oxidation studies: Exploring macrolide biosynthetic P450's as biocatalysts for sp<sup>3</sup> C-H oxidation

243rd National Meeting (2012)

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Synthesis of unnatural substrates for PikC oxidation studies: Exploring macrolide biosynthetic P450's as biocatalysts for sp3 C-H oxidation

Synthesis of unnatural substrates for PikC oxidation studies: Exploring macrolide biosynthetic P450's as biocatalysts for sp³ C-H oxidation