<jats:title>Abstract</jats:title><jats:p>A marine‐derived actinomycete, <jats:italic>Nocardiopsis</jats:italic> sp. (CMB‐M0232), obtained from a sediment sample collected at a depth of 55 m off the coast of Brisbane, Australia, yielded two new macrolide polyketides. Structures for nocardiopsins A and B were assigned by detailed spectroscopic analysis, degradation and chemical derivatization. A Marfey’s analysis revealed an unexpected acid‐mediated partial racemization of the <jats:sc>L</jats:sc>‐pipecolic acid incorporated within the nocardiopsins. The scope of this racemization was assessed against a selection of natural and synthetic <jats:italic>N</jats:italic>‐acyl pipecolic acids. While the nocardiopsins are not antibacterial, antifungal or cytotoxic, they do exhibit low‐micromolar binding to the immunophilin FKBP12, consistent with their structural and biosynthetic relationship to the immunosuppressive agents FK506 and rapamycin. The nocardiopsins represent a new point of entry into what has been a valuable, exclusive and reclusive region of bioactive chemical space—that surrounding the FK506/rapamycin pharmacophore.