Albert Eschenmoser (1925–2023) Autobiography Chapter 4: Professor at ETH—Etiologies and Prebiotics (1973–2008)

Around the time when the work on the chemical synthesis of vitamin B₁₂ reached its completion, it was the research on the biosynthesis of vitamin B₁₂ that really took off. The main reason for these advances was the advent of ¹³C-NMR spectroscopy in the early 1970s. Major players were the laboratories of David Shemin and A. Ian Scott in the USA, Alan R. Battersby in the UK, and Duilio Arigoni at ETH. It was already known that uroporphyrinogen III was an intermediate in B₁₂ biosynthesis, as in the case of porphyrins such as heme and chlorophyll, and that methyl groups on the periphery of the corrin ligand originated from methionine. ¹³C-NMR spectroscopy in 1972 brought not only confirmation of the previous findings but also provided a whole series of surprises that repeatedly revived B₁₂ biosynthesis research in the 1970s and 1980s. So was the (C-1)-methyl group at ring A found to originate from methionine, and the meso-carbon (C-20) to be removed from the molecule at some point of the biosynthesis. Both findings were quite startling, and both proved a hypothesis of mine, based on chemical plausibility, to be utterly wrong. The question of how Nature proceeded in this case was, of course, a challenge, not only for the bioorganic researchers on B₁₂ biosynthesis, but also for the corrin chemist at ETH. Retrosynthetic analysis by the natural products synthetic chemist and retro-bio-synthetic planning by the bioorganic chemist are so closely related that they can very well cross-fertilize each other in the planning of targeted experiments as well as in the interpretation of experimental observations. The chemical synthesis and biosynthesis of steroids and cyclic terpenes are a classic example of this synergy. Note: This is the opening passage of the chapter.