Showing papers in "Pure and Applied Chemistry in 1963"

Fast elementary steps in chemical reaction mechanisms

Abstract: A review is presented of studies of fast chemical reaction steps which were studied using various relaxation techniques. These studies include ligand substitution in metal complexes, proton transfer, and enzymatic hydrolysis. (D.L.C.)

Some recently developed fractionation procedures and their application to peptide and protein hormones

Abstract: In 1921 H. M. Evans injected a homogenate of anterior pituitary lobe tissues into rats and found that they gained in weight. From the time of this discovery twenty-three years passed before Evans, in collaboration with Li, reported the isolation of a growth hormone. Even today Li and his collaborators are making considerable efforts to improve the purification methods for this growth hormone. I think this fact illustra tes very well the difficulties encountered in attempts to fractionate protein and peptide hormones. However, the time and labour spent on such projects often prove tobe profitable. Some of the achievements in the field represent Iandmarks in the history of biochemistry. Two outstanding pioneering contributions which might be mentioned are the elucidation of the amino-acid sequence of insulin and the synthesis of vasopressin and oxytocin. Evidently in these cases, as in so many others, the isolation had to precede chemical analysis and synthesis. Without pure hormones only incomplete information can be obtained about the chemical structure; without extensive knowledge of the chemistry of the hormones their mode of action cannot be explained in chemical or physical terms. After these introductory remarks I hope to have made it clear that elaboration of powerful fractionation procedures is an important occupation. Within the last ten years my colleagues and I have studied the melanophore-stimulating hormone, vasopressin, oxytocin, corticotropin and its releasing factor, and recently the thyrotropic hormone. The biological assays have always been made by our colleagues in other laboratories while fractionation, chemical and physical characterization have been carried out in our institute at Uppsala. Two fractionation methods have been extensively used: zone electrophoresis and gel filtration. In addition to these procedures, counter-current extraction, ion-exchange, liquidliquid partition and charcoal chromatography have also been employed. In the fractionation schemes the various methods have been used in sequences that have proved to be extremely effective. Of all these methods gel filtration is the most informative since it often makes possible an estimation of the molecular size. Gelfiltration is a very versatile method that already has been applied to problems in many fields both in organic chemistry and biochemistry. I believe it is appropriate to discuss this method in more detail now since we have studied it extensively recently.

Force constants of small molecules

Abstract: The calculations ofnormal vibrations have two aspects. One is the use of calculated frequencies for the assignments of observed vibrational bands. In this case a deviation of several percent is permissible. Mizushima together with the author and co-workers have applied the Urey-Bradley force field to more than one hundred molecules and the assignments based on these calculations have been shown to be reliabJ.el, 2, The second aspect is to obtain accurate force constants. During the past few years the author and co-workers* have tried to obtain reliable and transferable force constants. This paper will review results so far obtained. Recently, Crawford, Overend, Scherer, Hisatsune et al. have madeextensive studies ~m the U rey-Bradley field. I t is a pleasure for the author to include these results in this review. For the potential function of molecules we started from the Urey-Bradley force field3 (UBFF) and tried to classify various molecules according to whether this type of force field is adequate or not.

Solubility constants of metal oxides, metal hydroxides and metal hydroxide salts in aqueous solution

Abstract: A critical compilation of solubility data on oxides, hydroxides, and hydroxide salts is presented. The literature up to 1957 and, as far as possible, since 1957 is covered. The methods used in deriving the solubility constants are discussed. A bibliography of 146 references is included. (D.L.C.)

Infrared spectral perturbations in matrix experiments

Abstract: In addition, there have been a substantial number of studies in which unusual. reactions have been discovered. These demonstrate unique possibilities in the study of the reactions and production of extremely reactive species. A number of these have been listed in the literaturelO and only two rt~cent examples will be mentioned. Milligau andjacoxll photolysed methyl az:ide in solid nitrogen to produce CH2=NH.

The coordination chemistry of 3d transition metal ions in fused salt solutions

Abstract: A review is presented of the spectroscopic studies of 3d transition metal ions and their complexes in chloride melts. An interpretation of the spectra on the basis of crystal field theory is given with criteria for selection of suitable host crystal lattices. A correlation of the results with electrostatic energies and crystal field stabilization energies is given. (D.L.C.)

Recent advances in the chemistry of large-ring conjugated systems

Abstract: One of the classical problems of organic chemistry concerns the question whether monocyclic hydrocarbons formally made up of alternating ~.;ingle and double bonds will show so-called \" aromatic \" behaviour. The bestknown example of this type of compound of course is benzene, which exhi.bits typical aromatic properties. Among these may be mentioned the fact that benzerre does not consist of distinct single and double bonds (as in formula I), but all the bonds are equivalent (as in formula II).

Perspektiven der Biogenese und der Chemie der Terpene

Abstract: Vor einigenJahrenwurde in einer "Faraday Lecture" die "History of the Isoprene rule" behandelt!, man hätte aber ebensogut sagen können "History of the Terpene Chemistry", denn der Fortschritt der Terpenchemie hängt eng zusammen mit der Entwicklung der IsoprenregeL Beide Gebiete haben sich stets fruchtbringend gegenseitig beeinflusst. Es lassen sich in der Geschichte der Terpenchemie und der Isoprenregel drei Perioden unterscheiden. Schon gegen das Ende der Vorgeschichte, 1884, als man weder für Isopren noch für ein einziges Terpen eine begründete Formel aufstellen konnte, bemerkte Tilden: "from the easy transformation of two C 5H 8 into C10H 16 and vice versa it appears probable that the molecule of terpilene is composed symmetrically of two halves, (C 5H 8) = (C 5H 8)''. Nur drei Jahre später beginnt mit dem Auftreten von Otto Wallach2 die erste Periode der Terpenchemie und der Isoprenregel, die bis zum Anfang der zwanziger Jahre dieses Jahrhunderts reicht. In diese Periode fällt der systematische Ausbau der Chemie der Monoterpene. Von fast allen bekannten Verbindungen dieser Reihe waren richtige Konstitutionsformeln bekannt. Wallach3 hatte 1887 als Aufbauprinzip der Monoterpene die Zusammensetzung aus zwei Molekülen Isopren vorgeschlagen, und auch für Sesquiterpene einen Aufbau des Kohlenstoffgerüstes aus drei Molekülen Isopren in Erwägung gezogen. Die Kohlenstoffgerüste der ersten zwei Sesquiterpene, deren Struktur eindeutig aufgeklärt werden konnte, a-Santalen (Semmler, 1910) und Farnesol (Kerschbaum, 1913), sind tatsächlich aus drei Isoprenresten zusammengesetzt, ohne dass es die Autoren nötig gefunden hätten diese Tatsache hervorzuheben*. Eine Isoprenregel als wegweisende Arbeitshypothese bei der Konstitutionsaufklärung gab es eben damals nicht. So kam es, dass im Rahmen der wenigen Arbeiten, welche in dieser Periode die Konstitutionsaufklärung von Sesquiund Diterpenen ernstlich anstrebten-aber wegen ungenügendem experimentellem Material noch nicht zum Ziele gelangten-Formein zur Diskussion gestellt wurden, die der Isoprenregel widersprachen.

Chemical structure and biological activity in the field of polypeptide hormones

Abstract: Many of the polypeptides which exert a regulatory function within the animal organism may be termed classical hormones: they are elaborated within special glands, are increted into the blood stream, and are thus transported to their points of action. Other regulatory polypeptides are often designated as \"tissue hormones\" 2• They originate in tissues whose physiological functions are not primarily hormone production (e.g. kidney, bloodplasma, brain, intestine, salivary gland etc.). Both types of compound will be included in this discussion. It is with Sanger's3 pioneering investigation into the structure of insulin (Figure 1) that organic chemistry has learned how to determine the nurober and sequence of amino-acid residues in polypeptide chains. This characteristic of a polypeptide is often called its primary structure and includes, of course, a detailed description of the configuration of each amino-acid residue. Depending on the nature of the molecular environment (neighbouring molecules in crystals, solvents, adsorbants, including cellular structures), the chains are known tobe coiled not in a random, but in a very distinct, manner: conformations induced by hydrogen bonds within the polypeptide backhone (peptide bonds) are called secondary structures, those determined by forces between the amino-acid side chains (and amounting to a further folding of secondary structures) are called tertiary structures4• Although monumental examples for the determination of secondary and tertiary structures of protein molecules in crystals have been provided by Xray examinations of the Garnbridge group5 (haemoglobin and cytochrome c), this method has not yet been applied to the few crystalline polypeptide hormones (many polypeptide hormones have not even been crystallized up to now, despite extensive purification, and, therefore, will not lend themselves to structure determination by this method). Methods for the . elucidation of three-dimensional architecture of polypeptides in solution are still in a rudimentary stage and may only yield information on certain details (e.g. hydrogen bonding of the phenolic -OH of tyrosine residues etc.) 6 • The contribution of the organic ehernist to the study of structure--activity relationships in the field of polypeptide hormones is at present restricted to the correlation of primary structure (amino-acid sequence) to biological activity. This is not too great a drawback, however, as primary structure

Some aspects of chemotaxonomy

Abstract: During the First International Symposium on the Chemistry of Natural Products Lord Todd1, in his Presidential Address, made some remarks that at first may have disturbed some of his audience. With regard to the structural elucidation of natural products he said: '' I dou bt myself whether it will nowadays lead to any major advances in science, however convenient · it may remain from the standpoint ofproducing exercises for Ph.D. students." I t is possible that Lord Todd will not prove to be a true prophet and, of course, bis intention was not to discourage anybody from dealing with such problems in the future. The elucidation of the structure and configuration of natural compounds will always remain a matter of great importance, but it is true that the main interest in natural product research is now gradually changing from problems of a purely chemical character to those of a biochemical and biological nature; this is what Lord Todd wanted to emphasize. It is interesting to compare monographs on plant colouring matters, terpenes or alkaloids, written 15-20 years ago with their recent equivalents. In spite of the many variations of the basic structures that have been discovered, the descriptive parts of the modern publications, useful as they are, appear somewhat monotonous. Very often recent work has simply extended the number of variations of a well-established basic structure. For example, the flavones have been shown to contain from nought to eight hydroxyl or alkoxyl groups attached to the basic 2-phenylchromone nucleus; about a hundred aglycones and almost as many glycosides have been isolated and, probably, there are hundreds yet tobe found. The chemical interest in the flavone field has already culminated and the major importance of these compounds now lies in their biosynthesis, relations to other natural products, distribution in the vegetable kingdom, biological function and physiological properties. The days have gone when the reputation of a ehernist was proportional to the number of structural problems he had solved, just as that of a Bornean headhunter used to depend upon the number of his trophies. The elucidation of the structure of a natural product should no Ionger be regarded as an end in itself but as a contribution to the clarification of general biological problems. To state this does not imply a discrimination against organic chemistry nor does it denigrate the value of the work clone by earlier generations of chemists.

Iron-containing antibiotics and microbic growth factors

Abstract: In the course of our systematic studies of the metabolic products of actinomycetes carried out in collaboration with the Institute of Special Botany of the ETH and with the Research Laboratories of the Pharmaceutical Department of Ciba Ltd. in Basel1, we have encountered a group of highly active, iron-containing antibiotics which were named ferrimycins2• U pon testing the activity of the culture filtrates and of the extracts containing these antibiotics erratic results were often obtained. This led eventually to the discovery that actinomycetes also produce iron-containing factors antagonistic to the ferrimycins3 • With the help of a simple and specific antagonism test, the detection and determination and, ultimately, the isolation of the antagonists was made possible. Moreover, the isolated iron-containing factors could in turn be used in the same test for the detection and determination of the ferrimycins and related antibiotics1• 3• The antagonism test is carried out in the following way: a filter paper strip impregnated with the antibiotic is placed at right angles on a second filter paper strip impregnated with the antagonist and both are then disposed on an agar dish. After inoculation with a suitable micro-organism and incubation, the action ofthe antagonist causes a wedge ofmicrobic growth to appear in the germ-free zone produced by the antibiotic. Under standardized conditions, the size of the wedge can be used for the quantitative determination of the antagonistic factors (Figure 1).

Studies on the synthesis of corrins

Abstract: The corrin structure is perhaps the finest gift that X-ray analysis has so far bestowed on the organic chemistry of low molecular weight natural products. It is the most recent member ofthat biogenetically related group of ligand systems which includes the two porphyrinoid structures, porphin and chlorin, and through which nature fulfils some of its fundamental biochemical processes. In the form of a cobalt complex, the corrin system c::mstitutes the structural nucleus of the B12 vitamins and, very probably, the B12 coenzymes. Research in the area of this group of natural products has been in a state of continuous and rapid development ever since vitamin H12 wa3 isolated in 19481.

Formation and dissociation of excited dimers

Abstract: Concentration queuehing of fluorescence is of general occurrence in the vapour state as well as in solution. Although its special features depend on th·: part:icular case it can be explained, in principle, by the prevalence of non-radiative deactivation processes in dimer aggregates of the ftuorescing single molecules. This results from a lower rate constant for radiative deactivationl, 2, and probably also from a higher rate constant for competing ncn-radiative processes in the lowest excited singlet state of a dimer in its mt:•st probable geometrical arrangement. In many cases, the ground state concentration of dimers is high enough to allow them to absorb the exciting light directly3, or to act as sinks in an energy transfer process from primarily excited Jnonomers4. In other cases with practically no association in the gr:mnd state, transient dimers may be created in the excited state by a diffusiun.al approach of excited and unexcited monomers. There are, however, exceptions to the general phenomenon of concentration quenching. One of these is represented by acridine orange5 where with the: disappearance of the original fluorescence, a second, weaker component ar:pears at higher concentrations. From the absorption spectra, appreciable gr:.und state aggregation must be concluded, obviously without complete su ppressiion of radiative deactivation. Q .. uite a different behaviour has been found in the case of pyrene6, 7, where a high concentration fluorescence component appears without any corresponding ground state association. The fluorescence spectra of heptane so lutiom. of this compound at different concentrations are depicted in Figure 1. Apparently, the well structured fluorescence in the u.v. and violet (which, by the way, shows the usual mirror symmetry to the absorption spectrum) is replaced at higher concentration by a structureless emission in the blue. Further investigations have revealed that: •: i) there is no change in the absorption spectrum within the corresponding ccncentration range; ~ ii) the decrease of the u.v. component as weH as the increase of the blue one with increasing concentration follow Stern-V olmer-type functions with the same half value concentrations in all solvents; ~iii) these half-value concentrations increase with solvent viscosity. [ t has been concluded from this, that the blue component is emitted by e:xcited dimers. These are created as transients, from pairs of excited and unexcited monomers in a diffusion controlled process. At elevated temperatures the excited dimers may dissociate again8.

Conformation and reactivity of medium-sized ring compounds

Abstract: Conformational analysis consists in the determination of the energy ( or of the enthalpy) of a conformation by the application of certain rules based upon theoretical considerations and confirmed by experience. Since in general the determination of the absolute energy of a given conformation is not possible, such analysis is limited to comparisons of energy contents of various conformations of one chemical species (molecules, ions, radicals, transition states) or of the conformations of closely related species. The most convenient parameters for the definition of the spatial arrangement ofthe atoms in a particle are bond distances (d), bond angles (ti) and torsion angles (T), because they are independent of the coordinate system. A large body of experimental evidence shows that in stable particles ( consequently not in transition states) the bond distances do not change appreciably upon modification ofthe conformation. For the purpose of conformational analysis one can, therefore, assume them tobe constant and consider only the energy variations due to changes in the bond angles and in the torsion angles. The increase in energy content which arises from a deviation of the actual values of the parameters from their most favourable values is usually called strain (S). The energy increase directly brought about by a deviation of the bond angles from their optimum (e.g. tetrahedral) angle, is known as classical or Baeyer strain (SB)· The one which is directly due to a deviation of the torsion angles is often termed Pi tzer strain ( Sp). A third and very important component of the strain proceeds from the repulsive interactions between non-bonded atoms (SN). These non-bonded interactions are determined by the same parameters d, {} and T, on which the other two types ofstrain mentioned above also depend. However, the expression which defines this dependence in the case of non-bonded interactions between atoms which are separated from one another by several bonds is so complex, that it is more convenient to represent the strain SN as a function ofthe interatomic distances r. Although the total strain can in principle be calculated on the basis ofthe three component strains which have been described above (Figure 1), quantitative conformational analysis is still quite unsatisfactory. For large molecules the deduction of strain from the variables {} and T requires extensive calculations. Such is already the case for the mediumsized cycloalkanes : in cyclodecane, for instance, there occur 405 nonbonded interactions. This difficulty can, of course, be overcome with the help of electronic computers. The most serious trouble is that the functions j 1, j 2, j 3 , f 4 etc. which connect the energy with the variables {} and T are only imperfectly known. Consequently, the considerable computing effort

Electronic spectra and electron transfer interaction between electron donor and acceptor

Abstract: The concept of intramolecular charge-transfer absorption band was developed by the present author and Tanakal, and also by Longuet-Higgins and Murrell2, by analogy with Mulliken's theory for intermolecular cases3. A :lominant characteristic of this concept is that systems where electron donating and accepting groups are combined with each other directly, or through a bridge of conjugated double bonds, generally show additional absorption bands characteristic of the interaction between electron donor (D: and c:.cceptor (A). In other words, it may be said that absorption bands of this kind appear additionally as the result of the contribution of so-called charge-tra.nsfer (abbreviated hereafter as CT) structures A --D+ to the resonance hybrid. This is schematically shown in Figure 1. In this figure, Ea('PG) and EcT(z/;cT) represent the energies (wave functions) of the ground ( or no-bond) and CT configurations, respectively. As the result of interaction between these two configurations, we can obtain the two energy Ievels W0 and J:Vh the transition between them corresponding to the CT band.

Fungal metabolism of certain aromatic compounds related to lignin

Abstract: Lignin is an important natural product which is found in plants of the Pte:ridophyta and Spermatophyta and which can be one of the main constituents of the plant. According to Erdtmanl it amounts to 25-30 per cent of spruce wood. I t is produced in several of the plant's tissues where it impregnates the cellulose fibres in cell wallstorender the tissue woody. In addition to confening rigidity on the plant, it protects the cellulose against chemical and physical attack. Since a large amount of plant material finds its way into soil, the fate of the various fractions of it is an important factor in the rnaintenance of soil structure and fertility. The general picture of decomposition of plant material in soil isthat the initial attack is on hemicelluloses and celluloses, with a relative accumulation of lignin, which probably becomes incorporated in the humic acid fraction of soil. The mechanism of lignin decomposition in nature is largely unknown and, until recently, had not been studied in detail, and it was in an attempt to gain some knowledge of this process that the sturliestobe described were undertaken.

Constitution of rifamycins

Abstract: Rifam)cins (formerly known as rifomycins) are metabolic products which have beer. isolated in the Research Laboratories ofLepetit Ltd., Milan, from cultures of Streptomyces mediterranei n.sp.l• 2, Under certain growth conditions rifamycin B is the main product of this group of compounds. I t is, however, unstable and is oxidized in buffered neutral solutions by mild oxidizing agents: o · even in air, to rifamycin 0 with loss of two hydrogen atoms. Rifamyci1 S is obtained from rifamycin 0 by acid treatment in aqueous solution ( :md also from rifamycin B if air is present), one molecule of glycolic acid being removed hydrolytically. Rifamycin 0 is transformed by mild reducing agents, e.g. ascorbic acid, into rifamycin B; rifamycin S gives by the sarne reaction rifamycin SV, the sodium salt ofwhich has found clinical applicati<'n under the commercial name rifacin ®.

Variation of the half-wave potential of organic compounds with pH

Abstract: From 19th International Union of Pure and Applied Chemistry Congress, London. A systematic introduction is presented to the subject of the variation with pH of the polarographic half-wave potential, which is probably the most readily measured electrochemical energetic parameter of organic compounds. Emphasis is placed on (a) the types of relationships observed for both reversible and irreversible electrode processes, (b) the mathematical formulation of these relationships, (c) the structural, mechanistic, kinetic, and environmental factors influencing such relationships, and (d) the presumptive physical causes for such relationships, e.g., the effect of pH on the electrochemical kinetics. Although the discussion is primarily concerned with behavior in aqueous solution, the conclusions drawn are equally valid for nonaqueous media in which hydrogen ion or some other Lewis acid can play a significant role. The half-wave potential for an organic electrode process may be independent of pH, or may vary lineanly or sigmoidally; other types of relationships observed are likely to be combinations of such effects. These variations may be due (a) to direct participation of hydrogen ion in the transition state involving the electroactive site in the organic molecule and the electron source, e.g., polarization of the bond to be broken, (b) to controlmore » of the state of reactants and/or products via participation in pre- and postequilibria, e.g., acid-base equilibria affecting the nature of the reactant or (c) to the effects of other kinetic, adsorption, steric, hydrogen-bonding and electrical double layer phenomena, as well as to combinations and variations of these effects. Solution composition factors influencing the observed variation of half-wave potential with pH include the ionic strength, the nature of the solvent, the specific identity of buffer components, and nonspecific salt effects. The implications of the experimentally observed half-wave potential-pH relations are considered in respect to the development of analytical procedures and the correlation of half-wave potential data. (auth)« less

Über kleine Ringe mit Kohlenstoffdreifachbindung - noch eine Chemie des "Als ob"

Abstract: Das Thema \"Kleine Ringe mit Kohlenstoffdreifachbindung\" beschäftigt mich seit 20 Jahren in einem ständigen Aufundab von Zweifel und Überzeugung. Dieser unbefriedigende und gleichzeitig stimulierende Dauerzustand hängt damit zusammen, daß die \" Cycloine \", von denen die Rede sein wird, niemals isoliert wurden, und daß nur Indizien auf ihre kurzlebige Existenz hinweisen. Da die zu erörternden Existenzialbeweise wohl einleuchtend, aber keineswegs bindend sind, bezeichne ich die Forschung hierüber in ihren gegenwärtigen Umrissen als eine Chemie des\" Als ob\". Ich wende mich zunächst den Cycloalkinen zu. Unter ihren niedergliedrigen Vertretemist das von Blomquistl t und gleichzeitig von Prelog2 synthetisierte Cyclononin Modellbetrachtungen zufolge noch gerade spannungsfrei, obwohl vier Kohlenstoffatome mit der Dreifachbindung zwischen den mittleren infolge der sp-Hybridisierung der a-Bindungen linear gestreckt sind. Dagegen zeigt das ebenfalls von Blomquist präparierte Cyclooctin3 eine merkliche Spannung, die in einer gesteigerten Additionsbereitschaft der Dreifachbindung evident wird. Nach eigenen Versuchen läßt sich der Kohlenwasserstoff mit Tetraphenyl-cyclopentadienon (Tetracyclon) regelrecht titrieren, da die rote Lösungsfarbe des cyclischen Ketons bei der eintretenden DielsAlder-Reaktion mit Cyclooctin verschwindet.

The structure and organization of the polysaccharides of yeast

Abstract: The polysaccharides present in the yeast cell are best considered in relation to the total organization of the cell both as regards their function and. their synthesis. Three polysaccharides may be extracted from the cells as distinc:t entities and these represent the storage material, glycogen, and the strue1:ural components, glucan and mannan. The three polysaccharides may be extracted from the yeast by cytolysing the cells with hot 3 per cent sodium hydroxide solution 1 which brings most of the mannan and a little of the glycogen into the solution and leaves an insoluble residue ofglucan membranes enclosing the bulk ofthe glycogen2, 3. The glycogen may then be dissolved from this latter material by hot 0·5 N aceric acid3, 4 and precipitated and purified by addition of alcohol. The mannan is precipitated from the alkaline solution as the copper complex which is decomposed by acid alcohol and the crude polysaccharide is purified by dissohring it in water and reprecipitating it with alcohol5• Alterna.tively, the cell wall of the yeast may be isolated free from the cell contents by breaking the cell with fine glass beads in a sonic vibratory mill and the resultant suspension fractionated by differential centrifugation2. U nder these conditions the cell wall may be analysed free from the glycogen which is ~.haken out of the cell envelope and appears in the supernatant with the other cell contents. The mannan and glucan may then be separated by gentle chemical extraction of the mannan from the wall fraction and the glycogen isolated from the cell contents without the use of strong alkali2 •

The biosynthesis of antibiotics

Abstract: The synthetic ehernist who is developing a useful drug usually has two objectives: .:o make it more efficiently, and to synthesize, by minor structural alterations, analogues which may have more useful properties. I wish to exo.rnine here the question whether the ehernist can, in principle, manipulate the process~$ of production of antibiotics by fungi with the same objectives in view. ~',ince antibiotics are, chemically speaking, randomly selected fungal rnetabolites, the general problern can be illuminated by information froJn thi~; w hole field (für a review of this topic cf. ref. 1). Antibioti::s are \"non-essential\" metabolites, since an organism can flourish wi1hout producing them, and their usefulness to the organism, which is still not clear, e.g. ref. I, is at any rate marginal. They represent a considerabl·~ consumption of materials and energy, and appear to draw usually on t!1.e same pools ofprecursors which are required for moreessential structural ü)mponents such as amino-acids, carbohydrates, nucleotides, and con1pounds found in energy-producing cycles, such as acetyl coenzyme-A. Antibioti1: production by an organism depends on a complex sequence of processes. The precursors must often be in a suitably activated state, i.e. in the form of derivatives such as pyrophosphates or coenzyme-A esters. The activating e 1zymes and coenzymes must also be developed by the organism, and. their synthesis represents a considerable additional consumption of pre•::ursors a nd energy. The chen List who tends to think in terms of stimulating production of a contpound hy feeding a normal biosynthetic intermediate may be greatly ove:r-simplifring the problem, as can be seen by a consideration of biosyw:hetic pr )Cesses. Biosynthe;is probably proceeds at defined centres inside the cell and an exogenaus ~ubstance must therefore be able to penetrate into the cell. Passage of a substance from the growth medium is not usually a process of simple diffu~ion but of \"active\" ·transfer: consequently, the cell may reject entirely some compounds offered to it even though these may be genuine biosynthetic intermediates. For example, isopentenylpyrophosphate is a known intermediate in polyterpene synthesis, but is not normally taken up fror:1 the m< dium. In order to utilize it the cell membranes h. ve to be disrup1:ed and the enzymes released, clearly not a feasible process for production purposes. The term \"intermediate\" is also often used very loosely to include substances whi( h contain the molecular fragment which is ultimately incorporated, e.g. acetic acid. In fact, such precursors are involved in an activated forn1 in con Lbination with a coenzyme or carrying extra groups such as

The total synthesis of a tetracycline

Abstract: discovered, and its pronounced activity against a broad spectrum of pathogenic organisms rapidly gained for it an outstanding place in medical practice. Shortly thereafter, oxytetracycline, or Terramycin, assumed a similar röle, as, later still, did tetracycline and 6-demethyltetracycline. Tetracycline can be obtained directly from natural sources, or from Aureomycin by removal of chlorine, while 6-demethyltetracycline is, so far, strictly a natural product. From the latter, 6-demethyl-6-deoxytetracycline, the prototype and simplest member of the entire group, can be obtained by removal of an hydroxyl group. The characteristic chemotherapeutic activity of all of these substances is essentially equivalent, and is strictly dependent upon the maintenance of all of the structural and stereochemical features of the general structure shown in Figure 1. That is to say, while the groups R 1 through R 4, situated along the upper periphery of the molecule, can be varied over a considerable range without effecting a substantial change in antibiotic properties, any modification elsewhere in the array leads to a marked decrease or complete loss of biological activity. The structures of Terramycin and Aureomycin were elucidated in our Laboratories a decade ago. Since that time, the complicated tetracyclic

N.M.R. studies of conformational equilibria in substituted ethanes

Abstract: Ear:.y studies of rotational isomerism e:mployed dielectric constant measurements and vibrational spectra. Most of such results have been summarized by Mizushimal. Problems studied include the energy differences and potential barriers between the various molecular configurations and the dependence of these quantities upon factors such as substituents, the solvent and the state ofthe sample. The basic question, which remains in large part, is the nature of the forces restricting intramolecular motions. Other mean:-~ of making such studies have been provided by the advent of high resolution nuclea.r magnetic resonance2 • 3. The present work deals with the application o::N.M.R. techniques to the rotational isomerism of substituted, liquid ethanes2-8. The factors governing the appearance of the N.M.R. spectra of these compounds include the relative energies of the three rotational isomers, the potential barriers to internal rotation about the C-C bond, and the chemical shifts and coupling constants characteristic of the magnetic nuclei in each rotamer2 • 3, These quantities can be obtained most completely and directly for a compound if the potential barriers are high enough that 1:he spectrum at lower temperatures is a superposition of spectra for the 1:hree rotamers. In the most general case of a substituted ethane, there will be three stable ::otational forms, as shown in Figure 1. Each ofthese forms has a mirror image,

Some important aspects of the chemistry of iso- and heteropolyanions

Abstract: stoicheiometric compositions is indicated. Figure 2 shows their correlation with the very distinct equivalent points of the potentiometric titration curve1• In this example, the degree of condensation increases with x, the final member of the series being the insoluble acid; a great many systems behave similarly, but for some others, particularly when the acid is weak and soluble, the proportion of condensed ions goes through a maximum. Such is the case

The sclerotiorin group of fungal metabolites: their structure and biosynthesis

Abstract: This lecture is concerned with a group of closely related fungal metabolites which has been extensively investigated in our Laboratories during recent years. These metabolites include sclerotiorin1-3, Cz1Hza05Cl (I), rotiorin4,5, C2aH24Ü5 (VI), rubropunctatin6, Cz1H22Ü5 (VII), monascorubin7, C2aH26Ü5 (VIII) and monascins, C21H2605 (IX). Since sclerotiorin is the most readily available member of this group its chemistry has been more extensively investigated than that of its associates. Further, the elucidation of the novel constitution of sclerotiorin greatly facilitated the structural de~:erminations of the less accessible pigments. Thus this new dass of compounds which are derivatives of the hitherto unknown, and as yet unsynthesized pyrono-system (X), is termed the sclerotiorin group of pigmentst.