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. Its initial isolation was followed by an extraordinarily concentrated period of about three years devoted to identifying that structure, culminating in a review of this chemistry in 1948 by Lemieux and Wolfram.[1] This review presents the structure as shown below (left). The modern rendering on the right is based on a crystal structure done in 1978.[2]‡
My interest in this was kindled by wondering how elucidating such a structure would be accomplished during the 1940s. None of the modern structural techniques were available then (NMR, MS, X-Ray); only IR and polarimetry (optical rotation). So how was it done? Well, the same way it had been done for the previous 100 years or so; degradation. In this case, into three smaller fragments, labelled A-C in the rhs diagram, and named streptidine, streptose and glucosamine in the original analysis.
I cannot help but note that the skills required to assemble a structure by degradation, and no use of NMR, MS or X-ray, were formidable, and very probably there are few chemists alive nowadays who could do a similar job (the motivation to do so would also be lacking). Assuming good crystals were available, solving such a structure nowadays using crystallography would only take 24 hours or so. And structures with 100+ stereogenic centres can now be done. When Woodward mused about the progress in chemistry, he might have had streptomycin in mind. I think it is worth remembering that the structural chemistry of 60 years ago was quite an intellectual achievement.
‡In fact the structure was first reported in 1968[3] but the coordinates in the CSD (Cambridge structure database) derive from the 1978 report.
In an earlier post, I discussed a phenomenon known as the "anomeric effect" exhibited by…
In the mid to late 1990s as the Web developed, it was becoming more obvious…
I have written a few times about the so-called "anomeric effect", which relates to stereoelectronic…
The recent release of the DataCite Data Citation corpus, which has the stated aim of…
Following on from my template exploration of the Wilkinson hydrogenation catalyst, I now repeat this…
In the late 1980s, as I recollected here the equipment needed for real time molecular…
View Comments
Fascinating study! I do wonder at times about the tremendous amount of chemistry, especially related to structure elucidation, that has been lost with the advent of modern spectroscopy and crystallography. A few examples: (1) every freshman student here in the US will be able to argue at length about electron occupancy and the shape of an sp3 hybrid orbital (which is of course totally imaginary), yet probably could not tell you how to separate gold from lead (2) When I was an undergraduate student at Illinois, I recall a cume exam given to the organic grad students that was essentially walking through the procedure that Fischer used to determine the structure of the elemental sugars - how many of us can do that today? (3) A few years back a grad student complained to me that he couldn't figure out if his compound contained a hydoxyl group or not based on his NMR. When I suggested running an IR, he was flabbergasted.
Is this always progress?