text: The structure of vitamin B was the first low-molecular weight natural product determined by x-ray analysis rather than by chemical degradation. Thus, while the structure of this novel type of complex biomolecule was established, its chemistry remained essentially unknown; exploration of this chemistry became one of the tasks of the vitamin's chemical synthesis. In the 1960s, synthesis of such an exceptionally complex and unique structure presented the major challenge at the frontier of research in organic natural product synthesis.
  Already in 1960, the research group of the biochemist  in Stuttgart had reconstituted vitamin B from one of its naturally occurring derivatives, cobyric acid, by stepwise construction of the vitamin's nucleotide loop. This work amounted to a partial synthesis of vitamin B from a natural product containing all the structural elements of vitamin B except the nucleotide loop. Therefore, cobyric acid was chosen as the target molecule for a total synthesis of vitamin B.
  Collaborative work of research groups at Harvard and at ETH resulted in two cobyric acid syntheses, both concomitantly accomplished in 1972, one at Harvard, and the other at ETH. A "competitive collaboration" of that size, involving 103 graduate students and postdoctoral researchers for a total almost 177 person-years, is so far unique in the history of organic synthesis. The two syntheses are intricately intertwined chemically, yet they differ basically in the way the central macrocyclic corrin ligand system is constructed. Both strategies are patterned after two model corrin syntheses developed at ETH. The first, published in 1964, achieved the construction of the corrin chromophore by combining an A-D-component with a B-C-component via iminoester/enamine-C,C-condensations, the final corrin-ring closure being attained between rings A and B. The second model synthesis, published 1969, explored a novel photochemical cycloisomerization process to create the direct A/D-ring junction as final corrin-ring closure between rings A and D.
  The A/B approach to the cobyric acid syntheses was collaboratively pursued and accomplished in 1972 at Harvard. It combined a bicyclic Harvard A-D-component with an ETH B-C-component, and closed the macrocyclic corrin ring between rings A and B. The A/D approach to the synthesis, accomplished at ETH and finished at the same time as the A/B approach also in 1972, successively adds rings D and A to the B-C-component of the A/B approach and attains the corrin ring closure between rings A and D. The paths of the two syntheses met in a common corrinoid intermediate. The final steps from this intermediate to cobyric acid were carried out in the two laboratories again collaboratively, each group working with material prepared via their own approach, respectively.