Vitamin B12 total synthesis
The total synthesis of the complex biomolecule vitamin B12 was first accomplished by the collaborating research groups of Robert Burns Woodward at Harvard and Albert Eschenmoser at ETH in 1972. It is considered a classic in the field of total synthesis of natural products. Work on the synthesis started 1960 at ETH, and in 1961 at Harvard, it was collaboratively pursued after 1965, and required the effort of no less than 91 post-doctoral fellows (mostly at Harvard) and 12 Ph.D. students (at ETH) from 19 different nations.
There are two variants of this synthesis, concomitantly accomplished in 1972. These two syntheses are intricately intertwined chemically, yet they basically differ in their overall strategy of creating the macrocyclic corrin ligand system of the vitamin molecule. The variant collaboratively pursued and finished at Harvard closes the macrocyclic corrin ring between rings A and B (the "A/B variant"), while the synthesis accomplished at ETH achieves the corrin ring closure between rings A and D by a photochemical process (the "A/D variant"). Woodward reported on the A/B variant in lectures published in 1968, 1971, and 1973, culminating in the announcement of the "Total Synthesis of Vitamin B12" in his lecture at the IUPAC Conference in New Delhi, July 1972.Eschenmoser discussed the ETH-contributions to the A/B variant in his Centenary Lecture, published in 1970, and presented the approach to the photochemical A/D variant of the B12 synthesis at the 23rd IUPAC Congress in Boston, published in 1971. A full report on the photochemical variant is given in a Science article of 1977 which is an extended English translation of a 1974 Naturwissenschaften article, based on a lecture given by Eschenmoser at the Chemical Society of Zürich.
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