John Norman Collie: Chemist and Mountaineer - Journal of Chemical

Chemistry Everyday for Everyone

John Norman Collie: Chemist and Mountaineer Ronald Bentley Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260

Just over a century has passed since Queen Victoria’s Diamond Jubilee in 1897 celebrated 60 of her 64 years on the throne of England. For science and technology, the Victorian Age was a time of great expansion of knowledge, a high-water mark being the Great Exhibition of 1851 and the building of the Crystal Palace. In Prince Albert’s words it was a time when the progress of invention was inevitably leading “to the realisation of the unity of mankind” (1). From the Exhibition stemmed the building of a complex of museums, colleges, and concert halls in the South Kensington district of London and the influence continued with the 1851 Fellowships. A truly fascinating character from that era was the chemist John Norman Collie. He was born on September 10, 1859, at Alderly Edge in Cheshire and died on November 1, 1942, at Sligachan on the Isle of Skye. Professionally he was a very significant figure, publishing more than 75 papers. He worked with Ramsay on the inert gases, constructed the first neon lamp, proposed a dynamic structure for benzene, and discovered the first oxonium salt. He is of interest today as the coiner of the word polyketide to describe polyketomethylene compounds, –(CH2–CO)n–, and for his suggestion that such compounds are involved in the biosynthesis of some natural products. Although long neglected, the term is widely used today in many disciplines. Moreover, his biosynthetic speculation was correct in its broad outlines; polyketomethylene structures such as CH3–(CO– CH2)n–CO–X (where X is a thiol structure such as coenzyme A or an acyl carrier protein) are actually formed in many biosynthetic processes. The polyketides now form a very large and diverse group of natural products, many having important physiological effects. A few examples are antibiotics (e.g., erythromycin, tetracycline), antifungals (e.g., griseofulvin), anthelmintics (e.g., avermectins), immunosuppressive materials (e.g., tacrolimus), cholesterol-lowering compounds (e.g., statins), and antitumor materials (e.g., doxorubicin). On the other hand, some polyketides are powerful toxins (e.g., coniine, aflatoxins). As the foregoing indicates, many polyketides have medicinal applications and are produced in large amounts by the pharmaceutical industry, usually by fermentation. For some polyketide antibiotics (e.g., erythromycin), genetic manipulation of the producing organism has the potential to provide new structures, hopefully with valuable properties.

Since two biographies focus on his mountaineering (2, 3), I will give only a brief account of his nonchemical life. His father had a minor role in the family cotton business, which was devastated when their supply was burned during Sherman’s infamous march through Georgia. The impoverished family moved to an estate near Aberdeen in 1865, where Collie’s father provided for shooting parties. During this time Col- J. N. Collie. This photo was most lie climbed his first peak—the likely taken in the early part of the modest 471 m high “Hill of Fare” period, 1902–1928, when Colabout 28 km west of Aberdeen. It lie was at University College, London, for the second time. was not until 1886, however, that he began technical rock climbing in Skye. He never looked back, climbing extensively in Skye, the English Lake District, Ireland, the Alps, Norway, and the Himalaya. On three expeditions to Canada, he carried out extensive mapping and is credited with the discovery of the great Columbia ice field. In 1921 at age 62 he attempted to join a reconnaissance expedition to Mount Everest. His biographers claim 79 first ascents for him, but since he did not record all of his climbs, the number must be substantially larger. Two mountains are named after him. The highest is Mount Collie, 3124 m, about 36 km northwest of Lake Louise in Yoho National Park, Canada. Less impressive is Sgurr Thormaid (Norman’s Peak), 927 m, one of the four “tops” of Sgurr na Banachdich, in the Black Cuillins of Skye. (Sgurr is a Gaelic word meaning a conical shaped peak.) He is also famous (or infamous) for a first ascent, with two companions, of Moss Ghyll in the English Lake District in December of 1892. Frustrated by a difficult foothold, he used an ice axe to remove a projection leaving a small square cut, known thereafter (until it was eroded away) as Collie’s Step. To cut into a rock was regarded by orthodox climbers as a crime. Collie received some criticism but cheerfully acknowledged that he had sinned.

Collie, the Mountaineer

In 1870, the family moved from Scotland to Clifton, near Bristol. For a time, Collie was a day boy at Clifton College, doing so poorly in classics that the head master “concluded that he had better move on to somewhere else and superannuated him from the College” (7 ). He then became a student at the newly opened (1876) University College, Bristol, and providentially came under the influence of the first professor of chemistry, E. A. Letts. This was a major turning point in his life, leading to his long career as a chemist. In a testimonial, Letts wrote that “My attention was drawn to him at once by his aptitude for chemistry. His progress was remarkably rapid” (3). In 1879, Collie published

Although a distinguished chemist, Collie is better known as a pioneer climber and explorer (2, 3). Other chemists and chemical engineers have been mountaineers, but their achievements do not approach those of Collie; examples are Sir Robert Robinson, credited with a first ascent of Mount Neeson in New Zealand (4 ), and George Ingle Finch, who pioneered the use of oxygen on Mount Everest (5 ). Collie’s other interests ranged widely “from incunabula to Chinese porcelain, from Japanese carving to vintage clarets” (6 ). He was also an accomplished water colorist and photographer.

Collie’s Career

JChemEd.chem.wisc.edu • Vol. 76 No. 1 January 1999 • Journal of Chemical Education

41


his first paper titled “On the Celestine and Baryto-Celestine of Clifton”. He had discovered baryto-celestine in rocks excavated for a railway tunnel that was part of a line linking Bristol to Avonmouth. When Letts was appointed to the chair of chemistry at Queen’s College, Belfast, in 1879, he asked Collie to accompany him as an assistant; in 1882 and 1883, they coauthored two papers. Letts found him “zealous and efficient as a teacher and a most enthusiastic worker at research” (3). Collie went to Würzburg in 1882 and obtained a doctor of philosophy degree with Johannes Wislicenus, publishing his fourth research paper in 1884 (8). For the next three years, he was Science Lecturer at the Cheltenham Ladies’ College. The main attraction seems to have been a salary of £ 200 per annum, but he was unhappy with the experience. His niece wrote that “Uncle Nor’s dislike of Cheltenham Ladies’ College probably arose from his intense dislike of Miss Beale (the headmistress) also, he was far from being a ladies’ man and probably found that schoolgirls in bulk were rather more than he could stomach” (3). When William Ramsay was appointed (1887) to the Chair of Chemistry at University College, London, he asked Collie to join him as assistant, thus relieving him from the difficulty of “schoolgirls in bulk”. This was the start of a long association with University College, broken only when he became Professor of Chemistry at the Pharmaceutical College, London, from 1896 to 1902. Collie returned to University College in 1902 as the first Professor in Organic Chemistry, and on Ramsay’s retirement (1912) also became Director of the Chemical Laboratories. He was retired unwillingly in 1928 and was succeeded by Robert Robinson. Collie covered much ground in his own research and he developed a substantial school of organic chemistry; since a complete bibliography is available (3, 7 ) only specific papers of special interest will be cited here. One of those he inspired, Professor S. Smiles, compared him with the great W. H. Perkin in flowery language: “If I must compare them, I would attempt an analogy, a poor one as all such must be. Collie I would regard as the landscape gardener, whilst Perkin was the energetic producer of really fine crops of new varieties. Collie took a very broad view of his subject, the relations of the various parts of it to one another, and of the whole to other branches of chemistry. He was no specialist, anything which savoured of narrowness was repugnant to his nature, but he was a true philosopher” (9). Because of his many other interests, another friend, Sir Herbert Jackson, once remarked, “Collie, it seems to me that you are a chemist only in your spare time” (7 ).

Inert Gases, X-rays In inorganic chemistry, he was concerned in the investigation of the inert gases, publishing four papers with Ramsay, one with Ramsay and Travers and two by himself—one in 1909 dealing with a curious property of neon and one in 1920 providing some notes on krypton and xenon. There is some mystery about his work with neon. Several people believe that he claimed to have discovered neon. However, in an account of chemistry at University College, which he delivered as a lecture in 1927, he makes no mention of any such involvement and credits only Ramsay and Travers (10): “The story of the discovery with Dr Travers of the three more gases in the atmosphere was one of unceasing hard work. It 42

was not until three years later that he [i.e., Ramsay] obtained Neon, Krypton, and Xenon from the air.” Neither did he claim neon’s discovery in a letter beginning “There are two things worth recording in any obituary notice of yours truly: 1) the first photograph ever taken by means of X-ray of metal in the human body I was responsible for it. 2) I constructed what was in reality the first neon lamp” (3). There is no doubt that he did construct the first neon lamp and demonstrated it at a Royal Society soiree in 1909. The “lamp” was essentially a discharge tube, certainly a product of his glassblowing skill. Although neon lamps were later developed commercially, Collie had no input into the marketing. As to the use of X-rays, there are two events involving Collie. After a demonstration at University College he asked that a photograph of his right hand be taken. It showed a small piece of metal (lead), apparently the result of the explosion of a toy pistol in his youth. Collie also X-rayed a woman patient, sent by the University College Hospital authorities, who stated that she had run a needle into her thumb. His picture (3) clearly revealed the position of the needle and was probably the first X-ray taken for surgical purposes. Although his work initially suggested the “transmutation” of hydrogen to neon with an electric discharge at low pressure (11), it could not be replicated by others; the observation of neon presumably resulted from leakage of air. Transmutation of radioactive elements was just being discovered at the time of this work (1913). In fact, with Ramsay he studied the “emanation” (radon) from radium and provided evidence for the presence of helium (12).

Structure of Benzene—the “Collywobble” The Collie era was one in which the structure of benzene was extensively debated. Kekulé’s famous paper was published in 1865 and has continued to attract attention even to the present day; during the last few years there has been much debate as to whether Kekulé’s ideas came to him in a dream. In 1897 and 1916, Collie published two papers on a “space formula” for benzene (13, 14 ). The model has been described (9) as “witness to his mechanical skill and clear thinking in three dimensions”. To a present-day chemist it seems too complex and highly mechanical. In any appraisal of its value, it has to be kept in mind that although electrons were discovered in 1897, their participation in chemical bonding did not become properly understood until much later; thus, the classic work of G. N. Lewis, “Valence and the Structure of Atoms and Molecules”, was not published until 1923. Collie proposed a dynamic model that could undergo a cycle of changes, passing through various “phases”. In an initial phase, the six carbon atoms were not coplanar, being placed at the apices of a regular octahedron. Each individual atom could rotate around its center and also move to different positions, creating a new ordering situation in another octahedron. At the midpoint of the cycle, the atoms were coplanar and the arrangement corresponded to the old “centric” formula. Two phases on either side of the centric formula corresponded to Kekulé double-bond structures. The movements of the carbon atoms in the octahedral model are roughly indicated by the projections shown in Figure 1, as are five of the phases. Clearly, the model is complex and is not easily comprehended. Collie’s colleague, A. W. Stewart, gave a detailed description in his ground–breaking text, Stereochemistry (15). It required approximately one thousand words, two line

Journal of Chemical Education • Vol. 76 No. 1 January 1999 • JChemEd.chem.wisc.edu


position. For ammonium salts, the reaction was as follows: (CH3) 4NX → (CH3)3N + CH 3X

X = OH or Cl

However, with phosphonium salts there were two possible reactions: (CH3)4POH → (CH3) 3PO + CH4 2(CH3) 4PCl → 2(CH3) 3P + 2HCl + C2H 4 When phosphonium salts with ethyl groups contained an additional group (e.g., benzyl, C7H7) the product depended on the number of ethyl groups; thus, when x = 1, y = 3 and x = 2, y = 2, the reaction was as follows: Figure 1. “The Collywobble”, Collie’s dynamic model for benzene. The drawings in the top row represent projections showing interconversion of two octahedral arrangements (left, initial, and right, final). They indicate the varying positions of the carbon atoms, numbered as 1 through 6. The mid-position has the six atoms coplanar and is shown in a plane at right angles to that of the paper. The five separate “phases”, indicating positions of hydrogens, are drawn in the bottom row. As indicated, the dynamic state involves two Kekulé structures and, at its midpoint, a “centric” structure.

drawings, and seven photographs; three of the photographs were mounted on a “fold-out” sheet and appear identical with those used in Collie’s 1897 paper (13). In 1919, the model was commercially available for the price of 50 shillings; in those days, this was a substantial sum and it is unlikely that it was purchased by many students. Six tetrahedra were necessary to represent the carbon atoms. In connection with other models, Stewart said that “wooden tetrahedra can be obtained from any carpenter”. Obtaining six wooden tetrahedra from a carpenter would not be easy in the USA today. Because of the various movements of the atoms, the model was known as “The Collywobble”. This was a nice play on words, since the Oxford English Dictionary defines “collywobbles” as “a disordered state of the stomach characterized by rumbling in the intestines”. The word, possibly formed from colic and wobble, dates from 1823. Its use for “butterflies in the stomach” was not uncommon when this writer was growing up in Great Britain before World War II; although known in the USA, it seems to have received little use.

Phosphonium Salt Decomposition In considering Collie’s organic chemical research, it has to be remembered that he had limited resources for the separation and purification of compounds (essentially crystallization and distillation) and that much reliance was placed on elementary analysis. Assignment of a structure depended on chemical intuition, conversion to known compounds, and color reactions. The elegant techniques of mass spectrometry and nuclear magnetic resonance were far in the future. A common feature in much of his work was the action of heat or an electric discharge on organic materials or gases (e.g., CO2, inert gases). Six of his papers have titles beginning either with “On the action of heat on…” or “The action of heat on…” and two titles contain “heat” as the final word. Seven titles contain the words “electric discharge”. As a student with Letts he had investigated the action of heat on phosphonium salts (16 ). These salts had several modes of decom-

(C7H7) x(C2H5)yPCl → (C7H7)x(C2H5) y-1P + HCl + C2H4 However, with a single ethyl group (x = 3, y = 1) in addition to the above process a further reaction occurred: 2(C7H 7) 3(C2H5)PCl → 2(C7H7)2(C2H5)P + 2HCl + C14H 12 This latter process leading to a tertiary phosphine was further developed and, in all, six new tertiary phosphines were characterized (17 ). At a much later date, Collie returned to phosphorus chemistry. His penultimate research paper in 1925 was concerned with reactions of triethylphosphine (18). Little or none of this work is found in today’s texts of organic chemistry.

Dehydroacetic Acid—Structure and Reactions His interest in polyketomethylene compounds has a tortuous history. In his Ph.D. work at Würzburg (1882), the ester of β-aminocrotonic acid (in his words, ethylic β-amidocrotonate) was obtained by the action of ammonia on ethyl acetoacetate (8 ). When ethyl β-aminocrotonate, 1, was distilled, a crystalline material, C10H13NO3, remained in the distilling flask. It could be hydrolyzed to an acid, C8H9NO3, which was decarboxylated by heat giving a dimethylpyridone, 3. Collie interpreted these results as indicating that the acid, C8H9NO3, was dimethylpyridone carboxylic acid, 2, R = H. In 1891 (19), he suggested a resemblance between the action of heat (red-hot iron tube) on ethyl acetoacetate, 4 (the enol form of which can be described as ethyl β-hydroxycrotonate), leading to dehydroacetic acid, and the formation of the ethyl ester of dimethylpyridone carboxylic acid, 2, R = C2H5, from ethyl β-aminocrotonate (in the decomposition of ethyl acetoacetate, one ester group is removed as part of the reaction). If this comparison was valid, dehydroacetic acid would have had structure 5. Aminocrotonate

2C6H 11NO2 → C 10H13NO3 + NH3 + C 2H5OH

Hydroxycrotonate 2C6H10O3 + H2O → C8H 8O4 + H2O + 2C2H 5OH

Scheme I


43


However, conductivity measurements indicated that dehydroacetic acid must lack a carboxyl group; hence, structure 5 had to be incorrect. Collie then proposed (8, 19) that dehydroacetic acid was tetraacetic acid lactone, 6, rather than 7 as suggested by Feist. He devoted much effort to verify his suggestion, more than 20 papers being concerned to some extent with this idea. He never conceded that he was wrong and the Feist structure was correct.

Scheme II

Tetraacetic acid, CH3(COCH2)3COOH, with its four –CH2–CO– groups, is an obvious linear polyketomethylene compound and the incorrect belief that its lactone, 6, represented the structure for dehydroacetic acid strongly influenced many of Collie’s biosynthetic proposals. Present-day explanations, based on the branched structure for dehydroacetic acid, 7, are less convenient for the biosynthetic theory. However, Collie was also influenced by reactions of diacetylacetone, (CH3COCH2)2CO, a compound with three –CH2–CO– groups, for which the structure was not in doubt. The story is further complicated by the fact that dehydroacetic acid was used as a source for diacetylacetone and during this work, a compound apparently containing a quadrivalent oxygen was discovered. When dehydroacetic acid, 7, was decarboxylated by boiling with strong (“fuming”) HCl, vacuum evaporation gave a chlorine compound, C7H9O2ClⴢH 2O, that had first been obtained in 1891 and was then thought to be a hydrochloride of diacetylacetone (20). Later, Collie and Tickle proposed that it was a salt of dimethylpyrone, 11, being an example of the quadrivalence of oxygen (21 ). It is now recognized as an oxonium salt of dimethylpyrone and has a resonance hybrid structure with a protonated dimethylpyrone functioning as a base. Collie is credited with the first discovery of such a structure. Although the empirical formula of the salt is C7H9O2Cl, it was obtained as a mono- or dihydrate.

salt, 11, was neutralized with solid Na2CO 3 to produce a solution of dimethylpyrone, 9. The dimethylpyrone solution was boiled and treated with excess of a “hot strong solution of barium hydroxide”. The sparingly soluble barium salt of diacetylacetone, 10, was precipitated. For further experiments (see later), it was “washed rapidly with hot water at the filter pump” and used as soon as it was cold. Under strongly alkaline conditions (syrupy NaOH, 150 °C), dehydroacetic acid gave much orcinol as well as an acid (22). In Collie’s explanation, the orcinol, 14, was thought to derive from diacetylacetone, 8, the latter being obtained from dehydroacetic acid (supposedly tetraacetic acid lactone, 6) by decarboxylation (compare the formation of dimethylpyrone). With the correct structure for dehydroacetic acid, 7, diacetylacetone formation is readily explained as 7 → 12 → 8. The conversion of diacetylacetone, 8, to orcinol, 14, is another important component of the biosynthetic speculations. The acid accompanying orcinol was hard to obtain but yielded orcinol and CO 2 on heating. It was said to be isomeric with orsellinic acid, 13, (without provision of analytical data) but was unequivocally stated not to resemble the latter; it was believed to be dihydroxyphenylacetic acid, 15, produced from tetraacetic acid, 16. However, at a later date Colliel[tated that “with alkalis the isomeric orcinolcarboxylic acid is formed” (23a) but made no mention of the prior paper in which the acid was believed to dihydroxyphenylacetic acid. Collie here seems disingenuous. With neither explanation nor new evidence, the supposed dihydroxyphenylacetic acid, 15, has become orcinolcarboxylic acid, 13—and it seems devious that the name orcinolcarboxylic acid was used rather than orsellinic acid. The step cutter of the mountains seems to have cut a number of corners in this matter! Using the accepted formula for dehydroacetic acid, the action of alkali in forming orsellinic acid is 7 → 12 → 13. Orcinol may also be derived by decarboxylation of orsellinic acid, 13 → 14.

Scheme IV Scheme III

As shown, diacetylacetone, 8, is an intermediate in the conversion of dehydroacetic acid, 7, to dimethylpyrone, 9, and the oxonium salt, 11; the conversion of diacetylacetone to dimethylpyrone, 8 → 9, was one cornerstone of the biosynthetic theory. (Collie represented the conversion of dehydroacetic acid to diacetylacetone as 6 → 8.) The diacetylacetone to dimethylpyrone reaction is reversible, and to prepare diacetylacetone, an aqueous solution of the oxonium 44

Formation of Naphthalenoid Compound from Diacetylacetone The conversion of two molecules of the barium salt of diacetylacetone to a naphthalene structure (22, 24 ) was another important observation for the biosynthetic theory. The salt was made into a paste with water, and “nearly dissolved in hydrochloric acid of about 15 per cent, leaving the solution faintly alkaline”. (One wishes for greater precision! This single phrase contains three vague terms: “nearly”, “about”, and “faintly”.) After removing “barium carbonate, &c”, a “first yellow compound” crystallized out, mp 108–109 °C. Collie believed it to be the benzenoid structure, 17. On vacuum concentration of the mother liquor, a “second yellow compound” identified as acetyldihydroxydimethylnaphtha-



lene, 19, was deposited. The first compound readily changed into the second so that “very little could be done with it”. The conversion occurred on boiling in ethanol or on standing in alkaline solution; presumably, the second compound formed on vacuum concentration of the mother liquor resulted from decomposition of the residual first compound.

Scheme V

To confirm the structure, Collie attempted to transform the second yellow substance to a simpler naphthalene structure: it was converted (acetic anhydride, 150 °C) to a diacetyl derivative, 20 Ac = CH3CO–, which was reduced with zinc dust in a current of dihydrogen. Two materials were obtained: one in 1893 (22) with mp 92–93 °C, the other in 1896 (24) with mp 67–69 °C. Attempts to characterize them as naphthalenes with either two or three methyl groups, 21 or 22, or two methyls and one ethyl group, 23, have the elements of farce. Some empirical formulas are incorrectly calculated from analytical data, and some of the theoretical values for % C and % H are incorrect. Expected % C and % H values given for the dimethyl derivative are actually those for the dimethylethyl derivative and vice versa. Although Collie concluded that he had obtained a dimethylnaphthalene, 21, the reported data are more consistent with a dimethylethyl structure, 23.

Role of Polyketomethylene Compounds in Biosynthesis From his many chemical explorations, Collie gained an appreciation of the reactivity of polyketomethylene compounds and in 1907 he proposed a rather general biosynthetic scheme for many natural products based on these reactivities (23a). A brief verbal presentation (23b) began as follows: “The group –CH2–CO– (which the author proposes to call the ‘ketide’ group) can be made to yield by means of the simplest reactions a very large number of interesting compounds, all belonging to classes which are amongst the compounds obtained from plants.” In the longer publication (23a) in the same year a very similar sentence was used but “ketide group” was replaced by “keten group”. The term keten had been coined only two years earlier (26 ), and it was Collie’s colleagues, Stewart and Wilsmore, who first provided evidence for the existence of keten itself in 1907 (27 ). Preceding Collie’s verbal presentation in 1907 had been a paper by Wilsmore titled “Ketene” (28). Collie attributed all manner of wondrous reactions to compounds containing “multiple keten groups”. For instance, from two keten groups, 24 → 25, addition of 2H2O was postulated to yield a carbohydrate-like molecule, 26, or from pyrone, 27, by way of 28 and 29, an actual pentose. Just why the reaction sequence was written to produce D-xylose, 30, was not explained.

Scheme VII

Scheme VI

This is all very disconcerting. Possibly mistakes were made in going from a (presumably) handwritten manuscript to the printed page. That such errors did occur is supported by the fact that in one of Collie’s papers (20) Feist’s name is given as First. Collie apparently never corrected these errors; similar analytical problems have been found elsewhere in his papers. Despite these previously unrecognized problems, the structure of the proposed naphthalene derivative as 19 has been generally accepted. In 1946, Kaushal reported that the condensation of diacetylacetone to the naphthalene structure could also be catalyzed by piperidine (25 ) but he did not encounter the first yellow compound of Collie. Collie never properly characterized the latter; it may have been structure 18, rather than 17.

Moreover, by reactions of hydration and dehydration, an accumulation of hydrogen or –CH2– could be obtained towards one end of a carbon chain and an accumulation of oxygen towards the other. In this way, it was believed that fatty materials could be obtained from compounds with multiple keten groups. These ideas had a grain of truth but in terms of reaction mechanisms were wide of the mark. More usefully, Collie emphasized the ability of keten-containing compounds to undergo condensation, as in the conversion of diacetylacetone, 8, to dimethylpyrone, 9, orcinol, 14, and the naphthalene structure, 19. In yet another reaction of disodium diacetylacetone and methyl iodide, Collie and Steele obtained seven products (pyrones, benzene and naphthalene structures, etc.) and wrote that the reaction is “of some complexity, but is an excellent example of how simple condensation of molecules containing the complex –CH2–CO– or its enolic form –CH=C(OH)– may be brought about in alkaline solution” (29).


45


What appears at first glance to be a 1948 summing up of Collie’s views came in a volume Recent Advances in Organic Chemistry (30). However, the publication history of this title is complex. The first of seven editions appeared in 1908 when its author, Alfred W. Stewart, was a colleague of Collie at University College in London; Collie provided an Introduction. The third edition in 1918 contained a new chapter on certain theories bearing upon the synthesis of compounds in vegetable and animal organisms. In a footnote, Stewart explained that when this chapter was under consideration, Collie had sent him a communication embodying some of his views which “appeared to me to necessitate the re-writing of the major part of the chapter”. Paragraphs derived from Collie’s notes were identified with a dagger (†). For the fifth and sixth editions (1927, 1931) and a reprint with additions, 1936, the work was presented in two volumes. For the final, seventh edition of 1948, it was stated that volume I could no longer be regarded as dealing with recent advances and was out of print; the seventh edition was, therefore, issued as Volumes II and III and a second author, Hugh Graham, was added. Graham noted that Stewart had died in June 1947, but that he had consulted with Graham prior to his death. The 1948 edition has only minor changes from that of 1918; there is still the same footnote indicating that Collie had contributed material (again identified with †), and much of the material is reprinted verbatim. The only significant changes are in a section dealing with photosynthetic formation of carbohydrates and in the deletion of some of the chemical material relating to the polyketides. Thus, although the 1948 date suggests that Collie might have made new contributions before his death in 1942, this so-called “Recent Advances” refers to material some 30 years old. Stewart was another remarkable individual from the late Victorian era who, like Collie, also had a second major life interest: under the nom de plume of J. J. Connington he wrote 27 novels, which were mostly detective stories (31 ). His first novel, Nordenholt’s Millions (1923), was a pseudoscientific thriller and was dedicated to “J. N. C.” (i.e., John Norman Collie). His contributions to biosynthesis (with Collie’s help) pushed the polyketide hypothesis beyond any reasonable limits. Thus, a C14 carbohydrate was postulated as precursor for the production of a monoterpene, C10H 16: C14H28O14 → C10H16 + 4CO2 + 6H2O Although the author of the text Stereochemistry (15), Stewart did not stop to wonder about the 212 stereoisomers of the postulated tetradecanose! Or, alternatively, two molecules of the branched-chain carbohydrate apiose, condensed to a (doubly branched) decanose, C10H20O10—or even ten formaldehyde molecules—yielded the decanose. Moreover, orsellinic acid was postulated to derive from a “methylheptose” (actually shown as the corresponding aldonic acid); by loss of three molecules of water, tetraacetic acid would be obtained in the enol form: CH3–CH(OH)–CH(OH)–CH(OH)–CH(OH)–CH(OH)–CH(OH)–COOH methyl heptonate

↓ CH 3–C(OH)=CH–C(OH)=CH–C(OH)=CH–COOH enol -tetraacetic acid (keto form = 16)

↓ Orsellinic acid, 13

46

As noted earlier, Collie never accepted the Feist formulation for dehydroacetic acid. Ironically, tetraacetic acid lactone, 6, was isolated as a natural product in 1967 from cultures of Penicillium stipitatum in which tropolone biosynthesis had been inhibited by ethionine. Triacetic acid lactone and its methyl derivative were also present (32). Under a variety of alkaline conditions, tetraacetic acid lactone was then shown to be converted to mixtures of orsellinic acid, 13, and orcinol, 14. With 63% H2SO 4 for 1 min at 100 °C, the major product was orcinol together with traces of orsellinic acid. Epilog It is tragic that neither Collie nor Stewart had any knowledge of developments in biochemistry and it is equally tragic that with two minor exceptions Collie’s ideas failed to stimulate the interest of chemists and biochemists. Twelve years after Collie made his proposal, Raistrick and Clark commented that his “observations do not seem to us to have received from biochemists the consideration that they deserve” (33). There is probably no single reason for the neglect that continued for more than three decades. One possible factor is that Collie always wrote in general terms rather than indicating specific compounds. He preferred to write about “interesting compounds all belonging to classes which are largely represented amongst the compounds obtained from plants” (23a) rather than give an example of a product from a designated plant. He could, for instance, have noted the pyrone chelidonic acid, obtained from Chelidonium majus. Moreover, at the time of his work natural products now known to be polyketides were few in number and perhaps his “acetyl groups” simply seemed too lowly to account for the formation of complex plant products. By the time of Stewart’s death in 1947, five years after that of Collie, the utilization of labeled acetate was under intensive investigation (34 ). It was clear that fatty acids were formed from an activated form of acetate by way of ketomethylene intermediates. In 1953, Birch and Donovan (35), being initially unaware of Collie, restated the polyketide hypothesis as a polyacetate process. Two years later, the incorporation of CH314COOH into 6-methylsalicylic acid in Penicillium griseofulvum was obtained with the predicted labeling pattern for the polyketide hypothesis (36 ). The polyketide pathway now has a fundamental place in the area of secondary metabolite biosynthesis. This is strikingly evidenced by the November 1997 publication of Chemical Reviews, a “thematic” issue guest-edited by D. E. Cane, under the title Polyketide and Nonribosomal Polypeptide Biosynthesis. Ten of the 13 articles deal with polyketides. Acknowledgments I thank I. M. Campbell and J. Vance for maps of and information on mountains in Scotland and Canada, respectively. The photograph of Collie was kindly provided by William C. Taylor, Emeritus Professor of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. Literature Cited 1. Weintraub, S. Victoria. An Intimate Biography; Truman Talley Books/Dutton: New York, 1987; p 214. 2. Taylor, W. C. The Snows of Yesteryear. J. Norman Collie, Mountaineer; Holt, Rinehart and Winston of Canada: Toronto, 1973.


Chemistry Everyday for Everyone 3. Mill, C. Norman Collie. A Life in Two Worlds; Aberdeen University Press: Aberdeen, 1987. The dust jacket of this book incorrectly gives Collie’s birth date as 1854. 4. Robinson, R. Memoirs of a Minor Prophet, Vol. 1; Elsevier: Amsterdam, 1976. 5. Finch, G. I. The Making of a Mountaineer; Arrowsmith: London, 1924. See also the later reprint, which contains further information on oxygen use in a memoir by Scott Russell; Arrowsmith: Bristol, 1988. 6. Williams, T. I. Robert Robinson. Chemist Extraordinary; Clarendon: Oxford, 1990; p 64. 7. Baly, E. C. C. Obituary Notices of Fellows of the Royal Society 1943, 4(12), 329. 8. Collie, J. N. Liebigs Ann. Chem. 1884, 226, 294; J. Chem. Soc. 1891, 59, 179. 9. Smiles, S. Quoted in Baly, E. C. C. Obituary Notices of Fellows of the Royal Society 1943, 4(12), 329. 10. Collie, J. N. A Century of Chemistry at University College; University of London Press: London, 1927. 11. Collie, J. N.; Patterson, H. S. J. Chem. Soc. 1913, 103, 419; Proc. Chem. Soc. 1913, 29, 217. 12. Ramsay, W.; Collie, J. N. Proc. R. Soc. 1904, 73, 470. 13. Collie, J. N. J. Chem. Soc. 1897, 71, 1013. 14. Collie, J. N. J. Chem. Soc. 1916, 109, 561. 15. Stewart, A. W. Stereochemistry, 2nd ed.; Longmans, Green: London, 1919.

16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.

Letts, E. A.; Collie, J. N. Proc. Chem. Soc. 1886, 2, 164. Collie, J. N. J. Chem. Soc. 1888, 53, 714. Collie, J. N. J. Chem. Soc. 1925, 127, 964. Collie, J. N. J. Chem. Soc. 1891, 59, 172. Collie, J. N. J. Chem. Soc. 1891, 59, 617. Collie, J. N.; Tickle, T. J. Chem. Soc. 1899, 75, 710. Collie, N.; Myers, W. S. J. Chem. Soc. 1893, 63, 122. (a) Collie, J. N. J. Chem. Soc. 1907, 91, 1806. (b) Collie, J. N. Proc. Chem. Soc. 1907, 23, 230. Collie, J. N. J. Chem. Soc. 1893, 63, 329. Collie, J. N.; Wilsmore, N. T. M. J. Chem. Soc. 1896, 69, 293. Kaushal, R. J. Indian Chem. Soc. 1946, 23, 16. Staudinger, H. Ber. Dtsch. Chem. Ges. 1905, 38, 1735. Wilsmore, N. T. M.; Stewart, A. W. Nature 1907, 75, 510. Wilsmore, N. T. M. Proc. Chem. Soc. 1907, 23, 229. Collie, J. N.; Steele, D. B. J. Chem. Soc. 1900, 77, 961. Stewart, A. W.; Graham, H. Recent Advances in Organic Chemistry, 7th ed., Vol. II; Longmans, Green: London, 1948. Kauffman, G. B. J. Chem. Educ. 1983, 60, 38. Bentley, R.; Zwitkowits, P. M. J. Am. Chem. Soc. 1967, 89, 676. Raistrick, H.; Clark, A. B. Biochem. J. 1919, 13, 329. Bentley, R. Ann. Rep. Chem. Soc. 1948, 45, 239. Birch, A. J.; Donovan, F. W. Aust. J. Chem. 1953, 6, 360. Birch, A. J.; Massy-Westropp, R. A.; Moye, C. Aust. J. Chem. 1955, 8, 539.


47

John Norman Collie: Chemist and Mountaineer - Journal of Chemical

Recommend Documents