Figure 7.

Examples of the atom replacement strategy in which carbonyl groups and/or the thioester are replaced with less-reactive isosteres to stabilize polyketide intermediates.A, select carbonyl groups are replaced with sulfur atoms, a more stable isostere. The thioester is also replaced with an amide bond to further stabilize the substrate. B, the carbonyl group of the phosphopantetheine unit can also be replaced with an oxetane group to stabilize the molecule. All of the replaced groups are highlighted in red. Note that the keto forms are shown here, but both tautomers are considered relevant.