Streptomycin is an antibiotic active against tuberculosis, and its discovery has become something of a cause célèbre. It was first isolated on October 19, 1943 by a graduate student Albert Schatz in the laboratory of Selman Waksman at Rutgers University. I want to concentrate in this post on its molecular structure.
The mechanism of the reaction of alkenes known as ozonolysis was first set out in its modern form by Criegee. The crucial steps, (a), (b) and (d), are all pericyclic cycloaddition/eliminations.
The Baeyer-Villiger rearrangement was named after its discoverers, who in 1899 described the transformation of menthone into the corresponding lactone using Caro’s acid (peroxysulfuric acid). The mechanism is described in all text books of organic chemistry as involving an alkyl migration.
During the 1960s, a holy grail of synthetic chemists was to devise an efficient route to steroids. R. B. Woodward was one the chemists who undertook this challenge, starting from compounds known as dienones ( e.g. 1 ) and their mysterious conversion to phenols ( e.g. 2 or 3 ) under acidic conditions.
Chemists love a mystery as much as anyone. And gaps in patterns can be mysterious. Mendeleev’s period table had famous gaps which led to new discovery. And so from the 1890s onwards, chemists searched for the perbromate anion, BrO 4 – . It represented a gap between perchlorate and periodate, both of which had long been known. As the failure to turn up perbromate persisted, the riddle deepened.
I mentioned in my last post an unjustly neglected paper from that golden age of 1951-1953 by Kirkwood and co. They had shown that Fischer’s famous guess for the absolute configurations of organic chiral molecules was correct. The two molecules used to infer this are shown below.
I wrote in an earlier post how Pauling’s Nobel prize-winning suggestion in February 1951 of a (left-handed) α-helical structure for proteins[cite]10.1073/pnas.37.4.205[/cite] was based on the wrong absolute configuration of the amino acids (hence his helix should really have been the right-handed enantiomer). This was most famously established a few months later by Bijvoet’s[cite]10.1038/168271a0[/cite] definitive crystallographic
Thus famously wrote Woodward and Hoffmann (WH) in their classic monograph about the conservation of orbital symmetry in pericyclic reactions.
My previous three posts set out my take on three principle categories of pericyclic reaction. Here I tell a prequel to the understanding of these reactions. In 1965, Woodward and Hoffmann[cite]10.1021/ja01080a054[/cite] in their theoretical analysis (submitted Nov 30, 1964) for which the Nobel prize (to Hoffmann only of the pair, Woodward having died) was later awarded.
Woodward and Hoffmann published their milestone article “Stereochemistry of Electrocyclic Reactions” in 1965. This brought maturity to the electronic theory of organic chemistry, arguably started by the proto-theory of Armstrong some 75 years earlier. Here, I take a modern look at the archetypal carrier of this insight, the ring opening of dimethylcyclobutene.