Iterative Assembly of Polycyclic Saturated Heterocycles from Monomeric Building Blocks

Polycyclic saturated
heterocycles with predictable shapes and structures
are assembled by iterative couplings of bifunctional stannyl amine
protocol (SnAP) reagents and a single morpholine-forming assembly
reaction. Combinations of just a few monomers enable the programmable
construction of rotationally restricted, nonplanar heterocyclic arrays
with discrete sizes and molecular shapes. The three-dimensional structures
of these constrained scaffolds can be quickly and reliably predicted
by DFT calculations and the target structures immediately decompiled
into the constituent building blocks and assembly sequences. As a
demonstration, in silico combinations of the building blocks predict
saturated heptacyclic structures with elementary shapes including
helices, S-turns and U-turns, which are synthesized in 5–6
steps from the monomers using just three chemical reactions.