This thesis is concerned with the synthesis of the class of interlocked molecular architectures called rotaxanes. Currently rotaxanes can be synthesized in high yields by exploiting noncovalent interactions between reacting fragments. The success of these supramolecular approaches are detailed in Chapter 1 and are contrasted with early attempts at their synthesis, which were low yielding. The novel properties of interlocked molecular architectures are also elaborated, emphasizing their potential as molecular level machines. Chapter 2 contains a detailed study of the hydrogen bond-directed synthesis of benzylic amid macrocycle-containing [2]rotaxanes. This task is performed by structural variation of the linear thread component in the standard five-component clipping reaction. The introduction of flexibility, non-optimal binding motifs, and the removal of key noncovalent interactions provide an insight into this remarkable process. In addition to analysis of the resulting yields of the [2]rotaxanes, the interlocked products are characterized by X-ray crystallography and ¹H NMR spectroscopy affording further insights into the specific structural requirements needed for subsequent interlocking. After a detailed study of this hydrogen bond-directed interlocking process, in Chapter 3 we synthesize a rotaxane, in high yield, whose components bear no formal recognition elements. In Chapter 4 we extend the concept of a MIA by demonstrating the function of a second-generation MIA based on a fumaramide template. The advantages of the fumaramide-based MIA are seen in the increased yield obtained for the benzylic amide-containing macrocycle rotaxane, but are slightly offset by the inclusion of a necessary photoisomerization step.