Fig. 6 |. Analysing the late-stage generation of molecular complexity.

Selected example of late-stage molecular complexity generation in total synthesis with accompanying complexity analysis, as scored by SPS (ignoring protecting groups). Key bond-forming steps (shown in the graphs) are highlighted in blue. a, The key cationic polyene cyclization in Johnson’s synthesis of (±)-16,17-dehydroprogesterone (3). b, Nicolaou’s late-stage pericyclic cascade to access endiandric acids B (7) and C (8). c, Heathcock’s evaluation of a biomimetic cascade to establish the dihydro-proto-daphnphylline (10) scaffold. d, Evans’ and Sorenson’s parallel approaches to FR-12877 (11, 12) through macrocyclization and transannular [4+2] cycloadditions. cat., catalyst.