bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum Statistical Mechanics
Authors: Goldman Maurice
Published: November 2023

NMR is not performed on a single or a small number of spins, but on a very large number, comparable with the Avogadro number. Even when one is interested in a molecular species with relatively few spins, the sample contains a large number of molecules of that species, all of which are observed simultaneously. What one observes in practice is the average response of the molecules, which is determined by an average over the states of each individual molecule. A common feature of all studies of condensed matter is that in the presence of many identical objects it is impossible to know exactly the state of the whole system, but that this relative ignorance is immaterial in so far as the properties of the system are not very sensitive to its exact state. The approach adapted to macroscopic systems is a statistical one, the correctness and fruitfulness of which is witnessed by the unfailing success of statistical mechanics. When dealing with quantum objects, the statistical approach must be adapted to their quantum character.
Fundamentals Of Relaxation Theory
Authors: Goldman Maurice
Published: November 2023

Relaxation is the name given to the phenomenon of evolution towards statistical equilibrium of macroscopic systems. The case in which we are interested is that when the whole system consists of two weakly coupled parts: the spin system consisting of all degrees of freedom dependent on the spin operators of the nuclei, and the lattice consisting of all other degrees of freedom of the liquid sample, associated with the molecular rotations and translations. Nuclear magnetic relaxation is in that case the evolution of the spin system towards thermal equilibrium with the lattice, and is called spin-lattice relaxation. The lattice is an ‘infinite’ thermostat, in the sense that its own thermal equilibrium state is not affected by the exchange of energy with the spin system taking place during relaxation.
Macromolecular Data Processing :For Area Detectors with Program System MADNESS
Authors: Messerschmidt Albrecht
Published: November 2023

During the last decade electronic area detector systems have become commercially available for data collection in X-ray crystallography of macromolecules. The area detector may be a multiwire proportional counter (MWPC) as in the system developed by Hamlin, Xuong and collaborators at the University of California, San Diego, USA (Cork, Hamlin, Vernon, Xuong, and Perez-Mendez, 1985) and in the Xentronics-Nicolet-Siemens system or a television-camera as in the FAST-diffractometer from EnrafNonius, Delft. During the last few years image plate systems (e.g. EMEL/Mar Research, Hamburg or Rigaku/MSC, Tokyo, Texas) have been developed especially for crystallographic applications.
Standardization -portability of crystallographic data
Authors: McMahon Brian
Published: November 2023

The title of this lecture refers to portability and standardization. Portability - the ability to transfer information from one location to another - is of course a desirable facility Standardization - the establishment of agreed terms for defining specific information - is the way to achieve this. There are three types of portability we may consider, and we shall see how the various standards required to enable each type of portability can come together to provide a high-level specification for a data structure that allows a highly portable form of data transfer in our science of crystallography.
Advances in computing for macromolecular crystallography
Authors: Bourne Philip E
Published: November 2023

In 1990 at the XVth IUCr Congress in Bordeaux, Keith Watenpaugh gave a paper with this same title. The paper outlined how crystallographers were applying current hardware and software technology to problems of macromolecular structure determination using X-ray diffraction techniques. Many of the innovations summarized at that meeting were subsequently presented in more detail at the Bischenberg Summer School on Crystallographic Computing (Moras, Podjarny, and Thierry, 1991). In small part this paper is an update to that report, tabulating several specific software developments that have occurred in the last two years. fn large part this paper is a commentary on parallel developments in the fields of macromolecular crystallography and computer technology, and makes the case for changes in the way we practice crystallographic computing if we arc to remain a first rate example of the success in applying computer technology to a scientific discipline.
The Cambridge structural database: current directions developments and future directions
Authors: Edgington Paul R
Published: November 2023

The Cambridge Structural Database (CSD) contains bibliographic, 2D chemical and 3D structural results for organocarbon compounds studied by X-ray or neutron diffraction. The Cambridge Crystallographic Data Centre (CCDC) which maintains the database was established in 1965. The CCDC is not only responsible for the maintenance of the database but also produces and distributes the software to enable the searching and analysis of the stored information. The complete package, database plus software, is referred to as the CSD system.
The application of the structure correlation method for studying reaction mechanism and transition state geometry
Authors: Kaftory Menahem
Published: November 2023

Roald Hoffinann’s famous quotation “There is no more basic enterprise in chemistry than the determination of the geometrical structure of a molecule. Such a determination, when it is well done, ends all speculation as to the structure and provides us with the starting point for the understanding of every physical, chemical and biological property of the molecule.…” provides us with a challenge. All the information about the molecular structure, whether it was obtained by theoretical calculations or by experimental methods, is available for us to try and deduce the relation between structure and physical, chemical or biological properties. The main problem is how to analyze the results and what kind of correlations exist between the available data and the relevant property. The understanding of a chemical reaction cannot be complete without knowing the structural variation of the reactants participating in the process. Molecules that are involved in a reaction have shape; they are not just a bunch of electron densities, and not a collection of representative numbers.
Structure–activity relationships of benzisoselanazoles
Authors: Piątek M , Oleksyn B J , Śliwinśki J
Published: November 2023

Selenium is an essential component of several biologically important macromolecules. Within the last few years it has been shown that selenium exerts protective and/or curative action against certain human diseases and maintains the integrity of immune reactions. Some of the organoselenium compounds synthesized recently, such as 2-phenyl-2H-benzisoselenazole-l,2 one-3, named Ebselen, were reported to possess remarkable biological activity. Selenium -oriented research has confirmed that many benzisoselenazoles exhibit anti -inflammatory, anti -cancer and immunostimulating activity. Ebselen displays protective action against inflammation and rheumatoid arthritis and has, therefore, been actively investigated and tested as a potential drug for clinical use.
Structure and stereochemistry of some ribofuranosyl nucleosides and related imidazole compounds
Authors: Briant C E , Jones D W , Shaw J D
Published: November 2023

Among the many nucleoside and nucleotide crystal structures that have been reported, rather few involve the five-membered imidazole ring (which has similarities with the five-membered ring in the common purines adenine, guanosine and inosine). Some of the 2,3-O-isopropylidene Nglycosylimidazole nucleosides synthesized by Professor G. Shaw and colleagues (Cusack et al., 1973; Mackenzie et al., 1976) are related to active intermediates in the de novo biosynthesis of nucleotides and to biologically active naturally occurring nucleosides, generally as β anomer.
Polymorphism of 6-methyluracil
Authors: Gladkikh 0. P , Masunov A E , Leonidov N B , Belsky V K
Published: November 2023

Most well-known synthetic biologically active and medical preparations are produced as powders, i.e. in the solio state. However, when such substances crystallize, several polymorphic modifications with different physical-chemical and physiological properties may form CMcCrone, 1963; Bernstein, 1989). Frequently polymorphism causes the variable bioactivity of different samples of one chemical compound.
The balance between order and disorder
Authors: Williams R J P , Da Silva J J R Frausto
Published: November 2023

In Chapter 1 we took as a historical starting point for the discussion of all observations concerning the material objects we sense around us the four ‘elements’ of certain Greek philosophers and scientists such as Aristotle (Fig. l. 1). We also noted the relationship to similar thinking in Chinese philosophy (Fig. 1.5). We have shown so far that, according to today’s views, three of the classical ‘elements’-air, water and earth-are more or less directly related to the physical states of materials (gases, liquids and solids). Moreover, as examined in Chapter 2, materials themselves of every kind are now known to be made from the fixed number of chemical elements of the periodic table (Fig. 1. 7). These elements came together in ordered, often shaped constructs to make molecular gases and condensed systems, and thence all chemical material things on Earth (and elsewhere), due to what we call ‘forces’, which can still be said to be related to the Greek idea of underlying ‘form’. The main forces of concern are those that we have labelled gravitational and electromagnetic (see Chapter 1). The fourth Greek ‘element’-fire (or heat and light)-can transform solids to liquids to gases; the Greeks connected it also to underlying ‘form’ and therefore made it similar in kind to the other three ‘elements’.
Basic procedures for matrix preparation
Authors: Dunkin Ian R
Published: November 2023

This chapter deals with procedures for sample preparation and the deposition of low-temperature matrices. It is assumed that equipment similar to that described in Chapters 2 and 3 is available. Some additional minor pieces of equipment are described in the following sections.
Spectroscopy, chirality, and oriented systems
Authors: Rodger Alison , Norden Bengt
Published: November 2023

Many of the questions we ask about chemical and biological systems relate to what shapes molecules have and how they interact with each other. New or modified methods are constantly being developed to address these questions, either in response to new problems or as the result of technical advances. The aim of this book is to show how circular dichroism (CD) and linear dichroism (LD) spectroscopies can be used to provide information about molecular structure and about interactions between molecules.
Total Synthesis of Cryptophycin C
Authors: Barrow R A , Hemscheidt T , Liang J , Paik S , Moore R E , Tius, M A
Published: November 2023

Discussion Points DMF Suggest a synthesis for compound 1. Explain the regioselectivity in the epoxide opening of step c. A considerable amount of compound 15 was formed when step e was carried out in the absence of 2,2-dimethoxypropane. Give mechanisms for steps h and u. Further Reading For studies on the regioselectivity in epoxide opening, see: M. Chini, P. Crotti, L.A. Flippin, C. Gardelli, E. Giovani, F. Macchia, M. Pineschi, J. Org. Chem.,1993, 58,1221; M. Chini, P. Crotti, C. Gardelli and F. Macchia, Tetrahedron,1994, 50,1261. For a review on ring-closure methods in the synthesis of natural products, see: Q. C. Meng and M. Hesse, Top. Curr. Chem.,1992, 161,107. For a modification of the allyl group removal procedure, see: A. Merzouk and F. Guibe, Tetrahedron Lett., 1992,33, 477.
The Total Synthesis of (—)-Balanol
Authors: Lampe J W , Hughes P F , Biggers C K , Smith S H , Hu H , Nicolaou K C , Koide, M E Bunnage and K
Published: November 2023

Discussion Points Rationalise the selectivity of the transformation of compound 4 into compound 5. What are the usual methods for deprotecting a tert-butylester? Give an alternative method of converting an alcohol into an azide. The cyclisation to give the hexahydroazepine 14 was carried out at ‘moderate dilution’ (0.02 M). What was the reason for this? Further Reading For other total syntheses of balanol and closely related analogues see; T. Naito, M. Torieda, K. Tajiri, I. Ninomiya and T. Kiguchi, Chem. Phami. Bull.,1996, 44,624; E. Albertini, A. Barco, S. Benetti, C. De Risi, G. Pollini and V. Zanirato, Synlett,1996, 29; K. C. Nicolaou, K. Koide and M. E. Bunnage, Chem. Eur. J.,1995, 1,454; K. Koide, M. E. Bunnage, L. G. Paloma, J. R. Kanter, S. S. Taylor, L. L. Brunton and K. C. Nicolaou, Chem. Biol.,1995, 2,601-8; C. P. Adams, S. M. Fairway, C. J. Hardy, D. E. Hibbs, M. B. Hursthouse, A. D. Morley, B. W. Sharp, N. Vicker and I. Warner, J. Chem. Soc. Perkin Trans. 1,1995, 2355; D. Tanner, A. Almario and T. Hoegberg, Tetrahedron,1995, 51,6061. For a series of seven articles concerning the biological activity of balanol derivatives, in particular their protein kinase C inhibition, see: J. S. Mendoza, L. Yen-Shi, G. E. Jagdman Jr, W. Lampe et al., Bioorg. Med. Chem. Lett.,1995, 5,pages 1839, 2015, 2133, 2147, 2151, 2155, 2211. The asymmetric synthesis of the 3-hydroxylysine used by Lampe et al.using Sharpless’ AD methodology can be found in P. F. Hughes, S. H. Smith and J. T. Olson, J. Org. Chem.,1994, 59,5799. For the application of a similar rearrangement to that shown in step j see: G. E. Keck, S. F. McHardy and J. A. Murray, J. Am. Chem. Soc., 1995, 117,7289.
Approach to the Synthesis of Pseudopterosins
Authors: Ghiron Chiara , Thomas Russell J
Published: November 2023

Discussion Points What is the purpose of the potassium t-butoxide in step d? What effect does the choice of Wilkinson’s catalyst have over the stereochemical outcome of the reaction? What is the mechanism of step I? Further Reading For a review on hydrosilylation see: I. Ojima in The Chemistry of Organic Silicon Compounds(Ed. S. Patai and Z. Rappaport), Vol. 2, J. Wiley and Sons, Chichester, 1989, pp. 1479-1526. Fmther studies on the synthesis of pseudopterosin A have been published recently: L. Eklund, I. Sarvary and T. Frejd, J. Chem. Soc., Perkin. Trans. 1,1996, 303.
Synthesis of a Protected Fluorocarbocyclic Nucleoside
Authors: Cotterill I C , Cox P B , Drake A F , Grand D M Le , Hutchinson E J , Latouche R , Pettman R B , Pryce R J , Roberts S M , Ryback G , Sik, V , Williams, J 0.
Published: November 2023

Discussion Points Give reasons for the stereoselectivity of epoxidation step e. What is the mechanism of the fluorination step n? Further Reading For a review on selectivity in enzymatic reactions, see: J.B. Jones, Aldrichimica Acta,1993, 26,105. For other studies on active site model for lipases, see: K. Naemurz, R. Fukuda, M. Murata, M. Konishi, K. Hirose and Y. Tobe, Tetrahedron: Asymm.,1995, 6,2385. For a review on the fluorination of organic compounds, see: 0. A. Mascaretti, Aldrichimica Acta,1993, 26,47.
Synthesis of Tropane Alkaloid Calystegine A3
Authors: Johnson C R , Bis, S J
Published: November 2023

Discussion Points What is the mechanism for the formation of compound 2? Explain the diastereoselectivity of the palladium-catalysed diacetoxylation of compound 3. Suggest an enzymatic route to ent-7from compound 6. The enzymatic asymmetrisation carried out on the azido derivative 5 or its diol derivative did not meet with success. Give a possible reason for the low enantioselectivity in this case. What is the mechanism for the formation of diol 9? A considerable amount of compound 14 is formed in the hydroboration oxidation steps r, s. Propose a possible explanation why there should be no strong directing effect of the a-oxygen in this case. Further Reading For references on the stereo- and regioselectivity in the palladium-catalysed diacetoxylation of dienes, see: J.E. Backvall, S. E. Bystroem and R. E. Nordberg, J. Org. Chem.,1984, 49,4619; J. E. Backvall and R. E. Nordberg, J. Am. Chem. Soc.,1981, 103,4959. For the combined use of enzymatic transformation and palladium chemistry in asymmetric synthesis, see: J. E. Backvall, R. Gatti and H. E. Schink, Synthesis,1993, 3,343; J. V. Allen and J.M. Williams, Tetrahedron Lett.,1996, 37,1859. For the use of enzymes in organic solvents, see: A. M. Klibanov, Acc. Chem. Res.,1990, 23,114; C.-S. Chen and C. J. Sib, Angew. Chem.,1989, 101,711. For the enzymatic transformation of tropone derivatives into sugars and related products, see: C.R. Johnson, A. Golebiowski, D. H. Steensma and M.A. Scialdone, J. Org. Chem.,1993, 58,7185.
Synthesis of an Enantiopure C-4 Functionalised 2-Iodocyclohexanone Acetal
Authors: Su Z , Paquette, L A
Published: November 2023

Discussion Points Explain the selectivity in the formation of the lactone ring in step a. What is the purpose of lithium chloride in step j? Further Reading For a modification of the Barton deoxygenation reaction using polystyrene-supported organotin hydride, see: W. P. Neumann and M. Peterseim, Synlett,1992, 10,801. For a review on the Barton—McCombie methodology, see: C. Chatgilialoglu and C. Ferreri, Res. Chem. Intermed.,1993, 19,755. For a review on the use of vinyl triflates in synthesis, see: K. Ritter, Synthesis,1993, 8,735.
Total Synthesis of (+)-Himbacine
Authors: Hart D J , Wu W -L , Kozikowski, A P
Published: November 2023

Discussion Points The reaction sequence starting from the dienolate derived from 2 led to a 8:1 mixture of the E:Z isomers corresponding to 3. Suggest a method to improve the stereoisomeric ratio. A significantly lower selectivity in the Diels--Alder reaction was obtained with the use of the alkyl ester corresponding to 4 or when no catalyst was used. Give reasons for this finding. Suggest a starting material for the synthesis of aldehyde 9. Further Reading For the control in the regioselective alkylation of dienolates, see: Y Yamamoto, S. Hatsuya and J. Yamada, J. Org. Chem.,1990, 55,3118. For the use of samarium diiodide in the Julia-Lythgoe olefination, see: G. E. Keck, K. A. Savin and M. A. Weglarz, J. Org. Chem.,1995, 60, 3194. For some reviews on the intramolecular Diels-Alder reaction, see: W.R. Roush, Adv. Cycloadd.,1990, 2,91; M. E. Jung, Synlett,1990, 4,186; D. Craig, Chem. Soc. Rev.,1987, 16,187; A.G. Fallis, Can. J. Chem.,1984, 62,183. For a review on the enhancement of rate and selectivity in Diels-Alder reactions, see: U. Pindur, G. Lutz and C. Ott, Chem. Rev.,1993, 93,741.
Synthesis of 5-Hydroxytiagabine
Authors: Andersen K E , Begtrup M , Chorghade M S , Lee E C , Lau J , Lundt B F , Petersen H , Sørensen P 0. , gersen, H Th
Published: November 2023

Discussion Points What governs the selectivity of the bromination of 3-methylthiophene 1? Propose a mechanism for the rearrangements occuring in step j. What is the purpose of the catalytic amount of potassium iodide used in step k? Further Reading For a recent account of the biological profile of tiagabine see: T. Halonen, J. Nissinen, J. A. Jansen and A. Pitkaenen, Eur. J. Pharmacol.,1996, 299,69.
Studies Towards the Total Synthesis of Rapamycin
Authors: Ley S V , Norman J , Pinel, C
Published: November 2023

Discussion Points Which enantiomer of diethyl tartrate is necessary in the Sharpless epoxidation step g to obtain the required stereoisomer? Further Reading For the synthesis of lactones via tricarbonyliron-lactone complexes, see: S. V. Ley, L. R. Cox and G. Meek, Chem. Rev.,1996, 96,423; G.D. Gary, S. V. Ley, C.R. Self and R. Sivaramakrishnan, J. Chem. Soc., Perkin Trans. 1,1981, 1,270; R. Aumann, H. Ring, C. Krueger and R. Goddard, Chem. Ber.,1979, 112,3644. For reviews on the use of iron carbonyl complexes, see: G.D. Annis, E. M. Hebblethwaite, S. T. Hodgson, A. M. Horton, D. M. Hollinshead, S. V. Ley and R. Sivaramakrishnan, Spec. Puhl. R. Soc. Chem.,1984, 50,148; J. Rodriguez, P. Brun and B. Waegell, Bull. Chem. Soc. Fr.,1989, 799.
Synthesis of a n-chiro-Inositol I-Phosphate
Authors: Jaramillo C , Chiara J-L , Martfn-Lomas M
Published: November 2023

Discussion Points Give a mechanism for the reactions covered in steps f and g. Propose explanations for the selectivities obtained in steps h, i and j. Rationalise the regioselectivity of the benzylation carried out in step k.
Synthesis of 7-Methoxycyclopropamitosene
Authors: Cotterill A S , Hartopp P , Jones G B , Moody C J , Norton C L , O’Sullivan N , Swann, E
Published: November 2023

Discussion Points Suggest bases suitable for employment in steps a and e. Give a mechanism for the indole ring formation in step b. In step b, along with the desired compound 3, a crystalline solid 10 was also obtained in 10-15% yield. An analytically pure sample provided the following data; C, 69.5; H, 5.4; N, 4.4%; mlzM+ = 311.The nujol IR spectrum displayed key peaks at 1734 and 2234 cm-1. The proton NMR spectrum gave, along with eight proton signals between 7.50 and 6.99 ppm, a 2-proton AB system (J = 12.3 Hz) centred at 5.21ppm and two 3-proton singlets at 3.92 and 3.68, a singlet integrating for 1 proton at 5.04 ppm. Propose a possible structure for 10 indicating a mechanism for its formation. What is the mechanism of the cyclopropanation step g? How does this step differ in the number of equivalents of base required with respect to a Shapiro reaction?
Total Synthesis of (+)- γ-Lycorane
Authors: Yoshizaki H , Satoh H , Sato Y , Nukui S , Shibasaki M , Mori, M
Published: November 2023

Discussion Points What is the structure of the palladium complex formed in reaction a? What is the rationale for enantioselectivity of the reaction? When NaH was used as the base in the palladium-catalysed alkylation step a, no enantioselectivity was observed. An enantioselective reaction was obtained with the use of a lithium base or alternatively via the transformation of 2 into its silylated derivative 6. Propose an explanation for this finding. Further Reading For a review on the selectivity in palladium-catalysed allylic substitutions, see: C. G. Frost, J. Howarth and J.M. J. Williams, Tetrahedron: Asymmetry,1992, 3,1089. For reviews on the Heck reaction, see: W. Cabri and I. Candiani, Acc. Chem. Res.,1995, 28,2; K. Ritter, Synthesis,1993, 8,735. For a review on enantioselective organotransition metal mediated reactions, see: S. L. Blystone, Chem. Rev.,1989, 89,1663.
Total Synthesis of (+)-Tetrahydrocerulenin
Authors: Miller M , Hegedus, L S
Published: November 2023

Discussion Points What is the mechanism of step c? Give reasons for the diastereoselectivity observed in step c. Suggest a synthesis of optically pure 3. What is the mechanism of the Baeyer-Villiger reaction? Further Reading For some references on the use of chromium carbenes, see: L. S. Hegedus, Acc. Chem Res.,1995, 28,299; M. A. Schwindt, J. R. Miller, and L. S. Hegedus, J. Organomet. Chem,1991, 413,143; L. S. Hegedus, Pure Appl. Chem.,1990, 62,691. For a review on the Baeyer-Villiger reaction, see: G. R. Krow, Org. React.,1993, 43,251. For the enzyme-catalysed version of this reaction, see: S. M. Roberts and A. J. Willetts, Chirality,1993, 5, 334; M. C. Pirrung and R. S. Wilhelm, Chemtracts: Org. Chem,1989, 2, 29; C. T. Walsh and Y. C. J. Chen, Angew. Chem,1988, 100,342. For the application of fluoride ion as a base in sugar chemistry, see: F. Santoyo-Gonzalez and F. Fernando-Mateo, Synlett,1990, 12,715.
Studies Toward the Total Synthesis of Cerorubenic Acid-III
Authors: Paquette L A , Poupart, M -A
Published: November 2023

Discussion Points What is the purpose of FeCl3 in step d? Give reasons for the high stereoselectivity observed in nucleophilic additions to the cyclopropane-containing system (e.g. step f). When the Wittig/ Grignard addition sequence was carried out in the inverse order, compound 10 was isolated instead. How can this result be explained? Explain the stereoselectivity and the complete regioselectivity observed in the Diels-Alder reaction of step n. Further Reading For further studies towards cerorubenic acid-III, see: L.A. Paquette, S. Hormuth and C. J. Lovely, J. Org. Chem., 1995, 60, 4813; L.A. Paquette, G. Y. Lassalle and C. J. Lovely, J. Org. Chem.,1993, 58,4254; L.A. Paquette, D. N. Deaton, Y. Endo and M.-A. Poupart, J. Org. Chem.,1993, 58,4262. For a review on anion-assisted sigmatropic rearrangements, see: S. R. Wilson, Org. React.,1993, 43,93. For reviews on the oxy-Cope rearrangement, see: K. Durairaj, Curr. Sci., 1994, 66,917; L.A. Paquette, Synlett.,1990, 2,67. For another application of oxidative dianion coupling in natural product synthesis, see: J. L. Belletire and D. F. Fry, J. Org. Chem.,1988, 53,4724. For a review on the enhancement of rate and selectivity in Diels-Alder reactions, see: U. Pindur, G. Lutz and C. Ott, Chem. Rev.,1993, 93,741.
Total Synthesis of 10-Decarboxyquinocarcin
Authors: Katoh T , Kirihara M , Nagata Y , Kobayashi Y , Arai K , Minami J , Terash S
Published: November 2023

Discussion Points Suggest a suitable base for the alkylation of the 2-formylpyrrolidine S. Considering the overall strategy adopted, what could be considered the main motive for using the D-threose derivative 2 in the synthesis? Attempts at carrying out the sequence depicted in step e with the benzyl protecting group originally present on the chiral auxiliary 2 did not give the desired product. Give a possible motive for this observation. Propose a mechanism for the cyclisation step g. Give two other methods of synthesising an isoquinoline ring system. The reduction of the isoquinoline nucleus of compound 7 proceeded with high stereocontrol. What factors could be responsible for the selectivity? What is the mechanism involved in the deprotection of the Troe group? The cyclisation sequence from alcohol 10 gave a single hemiaminal 11. Suggest an explanation for the stereochemical outcome of this reaction. Conversion of hemiaminal 11 into the nitrile 12 proceeds with retention of configuration. Propose a mechanism to rationalise this fact. Further Reading For a review of directing groups controlling metallation reactions see: V. Snieckus, Pure Appl. Chem.,1990, 62,2047. For a a synthesis of the related system (±)-quinocarcinamide see: M. E. Flanagan and R. M. Williams, J. Org. Chem., 1995, 60, 6791.
Total Synthesis of d,l-Isospongiadiol
Authors: Zoretic P A , Wang M , Zhang Y , Shen, Z
Published: November 2023

Discussion Points What kind of nOe would be expected to confirm the relative trans stereochemistry around the ring junctions in 5? Suggest a mechanism for the formation of the furan ring upon treatment of the epoxy-aldehyde derived from 7 with acid. What is the mechanism of the Rubottom oxidation? Further Reading For a review on manganese(lll)-based oxidative free-radical cyclisations, see: B. M. Snider, Chem. Rev.,1996, 96,339.
Total Synthesis of the Stemona Alkaloid (–)-Stenine
Authors: Wipf P , Kim Y , Goldstein, D M
Published: November 2023

Discussion Points Explain the diastereoselectivity in the formation of compound 2. In the absence of base, substantial amounts of compounds 10 and 11 were isolated from reaction d. Give an explanation for their formation and for the stereoselectivity observed in the formation of 4.
Enantioselective Synthesis of Deoxynojirimycin
Authors: Rudge A J , Collins I , Holmes A B , Baker, R
Published: November 2023

Discussion Points What should the absolute sterechemistry of the oxazolidinone benzyl group of compound 1 be in order to furnish the required product 2 under the conditions reported? Suggest a structure for compound 6. Rationalise the stereoselectivity observed in step g. What is the mechanism of the Martin sulfurane step k leading to compound 11?
Synthesi of (–)-PGE2 Methyl Ester
Authors: Taber D F , Hoerrner, R S
Published: November 2023

Discussion Points Propose a structure for the reactive intermediate formed in step g before the addition of water. Treating intermediate 7 with benzoic acid resulted in the formation of compound 17. Suggest a structure for 7 and the mechanisms by which it gave both diazoketone 10 and benzoate ester 17.
Total Synthesis of (+)-Myrocin C
Authors: Chu-Moyer M Y , Danishefsky S J , Schulte, G K
Published: November 2023

Discussion Points What is the mechanism of step b? Propose an alternative method of carrying out the transformation achieved with 3,3-dimethyldioxirane in step c. Rationalise the stereoselectivity of the reduction in step d. Bearing in mind the observation that on treating the tosylate 18 with tert­butyl lithium at -78 °C compound 19 was obtained in 74% yield, suggest a mechanism for the formation of 13 from 12.
Synthesis of a Fragment of (+)-Codaphniphylline
Authors: Heathcock C H , Kath J C , Ruggeri, R B
Published: November 2023

Discussion Points Explain the loss of enantiomeric excess observed in the transformation of 2 into 4. A small amount of compound 14 is formed under the Reformatsky condition of step i. Suggest a mechanism for its formation. Suggest a mechanism for the formation of compound 10 and for the demethylation of the intermediate carbocationic species 9. What is the role of DIBAL in the Grob fragmentation of step n? Give a mechanism for the formation of compound 13. Suggest a reason for the necessity of transforming amine 11 into the urea derivative 12.
Economic analysis of bioenergy options
Authors: Ravindranath N H , Hall D O
Published: November 2023

In previous chapters the potential and need for modern bioenergy options, the potential beneficial environmental and socio-economic impacts, and the feasibility of the technologies have been discussed. However, for any technology to find acceptance and spread it must be economically viable apart from being technically sound. There are image problems for all alternative energy technologies, including bioenergy, such as high capital and operational costs, limited potential, and the idea that they are not yet ready for large- scale dissemination.
Prevalence of Migraine in the Primary Care Setting
Authors: Couch J , Hettiarachchi J
Published: November 2023

According to general population surveys, migraine is a prevalent and debilitating disorder, affecting 13% of the adult population (18% of women and 7% of men), in the United States. Patients with migraine utilize healthcare resources to a greater extent, although migraine may not be the primary reason for the visit to the healthcare provider. The prevalence of migraine in patients seeking medical care is unknown, but may be higher than that in the general population.
The role of the immune system in cancer
Authors: Stevenson Nigel J , Johnston Jim
Published: November 2023

Infection and chronic inflammation predisposes us to many forms of cancer and the response to malignant disease shows many parallels with inflammation and wound healing. The cells involved in inflammation are detected in a range of common cancers, together with the inflammatory cytokines and members of the chemokine ligand/receptor systems. Many cancers occur more frequently with certain infectious diseases; examples include Helicobacter  pylori infection, human immunodeficiency virus, hepatitis, and human papillomavirus (HPV). The longer the infection and inflammation persist, the higher the risk of associated cancer. Chronic inflammatory conditions such as inflammatory bowel disease, have a five-to sevenfold higher incidence of colon cancer, as a result of the immune response causing colonic epithelium to become transformed. Therefore, understanding these disease processes may lead to better prevention and treatment for cancer. The theory of immune surveillance suggests that the immune system continually recognizes and eliminates tumours; when a tumour escapes immune surveillance and grows too large for the immune system to kill, cancer can result. Immune surveillance is most likely to be successful against virusinduced cancers that express foreign peptides. However, tumours vary greatly in their immunogenicity, and even those with antigens, which can be recognized by the host immune system, can evade immune elimination.

Lack of tumour rejection by intact immune systems is not always due to the absence of antigens that can be recognized or to the absence of T cells that can recognize those antigens. Tumour-specific lymphocytes can be found in the blood, draining lymph nodes, and in the tumour itself of patients with actively growing tumours. These lymphocytes can kill tumour cells in  vitro but fail to do so in  vivo. The presence of these cells has allowed immunologists to identify antigens on some tumour cells.
Pulmonary infections in cancer patients: diagnosis, aetiology, and principles of treatment
Authors: Karlin Lionel , Lefebvre Aurelie , Azoulay Elie
Published: November 2023

Pulmonary complications are a major cause of morbidity and mortality in patients with cancer and particularly in those with haematological malignancies (Hilbert et  al. 2001). Nearly one-third of these patients are affected, with a mortality rate of up to 50% (Wardman et  al. 1984). Pulmonary complications account for most of the intensive care unit (ICU) admissions in critically ill cancer patients (Kress et  al. 1961; Blot et  al. 1997). Mortality in the ICU is extremely high, particularly in bone marrow recipients and when mechanical ventilation is required (Ewig et  al. 1998; Rabe et  al. 2004). Many disorders can lead to respiratory symptoms in cancer patients. Several interlinked disorders may occur in combination in the individual patient. Infections are the leading causes of respiratory symptoms (Azoulay et  al. 2004), not only because the respiratory tract is the main route of entry for many microbial agents, but also because host defences are impaired by the underlying disease (e.g. hypogammaglobulinaemia in chronic lymphocytic leukaemia and multiple myeloma) and anticancer treatments, which can induce neutropenia and immune dysfunction. Other causes include chemotherapy or radiation-induced pulmonary toxicity, leukaemic infiltration (Cordonnier et  al. 1994), and intra-alveolar haemorrhage. Early aetiological treatment improves the chances of survival (Von Eiff et  al. 1995). This, together with the large number of possible causes, requires a rapid and orderly diagnostic evaluation. The most likely causes should be identified based on the underlying disease (e.g. Legionella  pneumophila pneumoniae is common in hairy cell leukaemia) and previous treatments (e.g. fludarabine therapy is associated with pneumocystis jiroveci pneumoniae (PCP).
Bone and joint infections
Authors: Laverick Michael
Published: November 2023

abstract

Bone is a common site for metastatic cancer and the majority of malignant bone tumours are secondary. Primary bone tumours, though uncommon, do present a formidable challenge as they occur most frequently in a relatively young age group. Progress in chemotherapy allowing better disease control, progress in imaging allowing better pre-operative planning, progress in bioengineering improving prosthesis design, and increased understanding of distraction histogenesis have radically altered the approach to the treatment of primary malignant bone tumours. Disease for which only amputation surgery was offered in the past, often with poor outcomes, can now be approached by a combination of chemotherapy and surgery and, while amputation remains an option in many cases there are a wide variety of limb-sparing surgical options available. Bone defects created by radical surgical excisions can be treated by metal endoprostheses, a variety of allografts (including osteoarticular allograft, intercalary allograft, and allograft–prosthesis composites), arthrodesis, rotationplasty, free vascularized fibular transfer, and distraction osteogenesis techniques. Infection in the reconstructed limb remains a feared complication common to all these techniques and is the commonest cause of failed reconstruction. Avoidance of infection continues to drive the choice of reconstruction technique and also developments in technique and prosthesis design. Bone and joint infection is more common in the immune-compromised host. Although the literature relating specifically to the cancer patient is sparse it seems that they will be at increased risk of infection after injury or orthopaedic procedures.
Virus infections
Authors: MacMahon Eithne , Jeyaratnam Dakshika
Published: November 2023

This chapter addresses viral infections including human immunodeficiency virus (HIV) in patients with solid and haematological malignancies, including those treated with haematopoietic stem cell transplantation (HSCT). The greater frequency and severity, atypical presentation and the challenges of diagnosis, management, and prevention of virus infections in cancer patients are discussed, with separate sections highlighting the specific issues in HSCT and HIV infection. The differential diagnosis of clinical syndromes is tabulated, supplemented by specific discussion of the most important viruses. Herpes simplex virus (HSV) and varicella zoster virus (VZV) are covered under skin and soft tissue infections (Chapter 9). The role of viruses in the pathogenesis of malignancy is discussed elsewhere, eg. Chapter 2. Many factors contribute to the risk of virus infection in cancer patients. The underlying malignancy and the therapy administered diminish host defences, an effect greatly exacerbated by HSCT, graft versus host disease (GVHD) and consequent immunosuppressive therapy. The patient’s age, sex, prior and persistent infections, immunization history, underlying illnesses, travel history, hobbies, animal contact, and risk behaviours, together with geographical location, season and nosocomial or community exposure to circulating viruses all contribute to each patient’s ever-changing susceptibility to virus infection and disease. The usual principles of infectious diseases may no longer apply. Cardinal diagnostic features that reflect host response, rather than the infection per  se, may be absent, e.g. parvovirus or measles infection without fever or rash. Patients are prone, not only to more severe manifestations of locally circulating viruses, but also to life-threatening consequences of usually benign opportunistic pathogens, e.g. cytomegalovirus (CMV). Expectations of finding a single unifying diagnosis to account for signs and symptoms are less, especially in the severely immunocompromised, where several different infectious agents may simultaneously be contributing to the clinical picture.
Infections of the central nervous system
Authors: Scott Geoff
Published: November 2023

Cancer and its chemotherapy lead to increased susceptibility to infections. Central nervous system (CNS) infections are rare but commonly fatal and a disappointing outcome in patients who may have otherwise been successfully treated for their tumours. The degree of immunosuppression conferred by the neoplastic disease and its treatment determine what sort of infections can be expected. The greater the degree of immunosuppression, the more likely that infection can arise from otherwise harmless saprophytes. Primary CNS infections with traditional virulent organisms such as the meningococcus and Haemophilus  influenzae are quite rare in otherwise healthy people so that, although they may occur in patients with cancer, the absolute number of individuals with malignancy who develop community-acquired ‘virulent’ infections is very low. Nevertheless, B-lymphocyte diseases such as myeloma particularly predispose to pneumococcal infections. CNS infections are most likely to occur in those who are most immunosuppressed by disease aggravated by chemotherapy, allogeneic or autograft transplantation, radiation, corticosteroids, splenectomy, or underlying human immunodeficiency virus infection. They may also follow neurosurgical procedures.
Cognitive problems
Authors: Baldwin Tony , Demellweek Colin , Rankin Peter , Carleton Fran
Published: November 2023

Cognition is a term used to describe all of our thinking skills and is comprised of different cognitive domains including memory, language, visual-spatial processes and motor planning – a group of organizational/planning skills known collectively as ‘executive function ‘. All of these skills are dependent on the integrity of brain function, therefore, a brain injury can adversely affect specific or general cognitive skills. In healthy adults, cognitive skills are developed to the extent that they are specialized functions which are dissociable on neuropsychological testing and each cognitive domain is primarily associated with different brain regions. For example, the region in the temporal lobe known as the hippocampus, is particularly important for certain types of memory function, whereas the prefrontal cortex is fundamental to executive skills.
Discussion summary Neurobiology of neuropathic pain
Authors: Treede Rolf-Detlev
Published: November 2023

This is probably the most fundamental question arising in this session. It was argued that the current IASP definition, ‘ Pain due to lesion or dysfunction of the nervous system’, is of little practical use, because it has no clear boundaries. In other words, using this definition it would be very hard to find any pain that cannot be considered to be neuropathic. This is primarily due to the presence of the term ‘ dysfunction’, which has no clear definition itself and may easily be confused with the normal plasticity of the nociceptive system. In addition, there are lesion sites in the nervous system that may induce pain by clearly nociceptive mechanisms: the muscle pain in rigor or spasticity. Thus, the range of potential lesion sites that may be implied in the generation of neuropathic pain calls for a more precise definition. The IASP special interest group on neuropathic pain (NeuPSIG) has founded a subcommittee on classification that is working on both a revised definition of neuropathic pain that is more precise and a grading system that reflects the degree of certainty with which the presence of neuropathic pain can be determined in a given patient. The current working definition is ‘ Pain arising as a direct consequence of disease or lesion affecting the somatosensory system’ .
Clinical assessement of hyperalgesia and allodynia in episodic migraine versus chronic migraine interictally and ictally
Authors: Boudreau Guy
Published: November 2023

Allodynia is defined as a pain sensation evoked by stimulation intensities that do not normally evoke pain: hyperalgesia is defined as an increase in pain sensitivity to normally painful stimuli. Allodynia and hyperalgesia can be evoked at sites adjacent or remote from an injury site (secondary hyperalgesia). Secondary hyperalgesia is called touch-evoked pain and can be detected in areas of the skin adjacent to an originating somatic lesion, or in a somatic region remote from an area of visceral damage. Burstein demonstrated that sensitization of second-order trigeminovascular neurons drives the cutaneous allodynia and/or hyperalgesia. Based on those findings, he expected migraine to be associated with central sensitization, the clinical manifestation of which should be extra cranial sensory hypersensitivity.3
CNS adverse events in patients treated with triptans Side effect or symptom?
Authors: Albert, K S , Parsons B
Published: November 2023

Somatic symptoms, mostly fatigue and dizziness, are a common complaint in patients diagnosed with migraine. However, these symptoms often overlap with the central nervous system-(CNS) type adverse events (AEs), such as asthenia and somnolence, which are often associated with the resolution of a migraine attack.Treatment of migraine with a triptan, although effective, can be associated with transient AEs including CNS AEs. Therefore, it may be difficult to separate the effects of the medication from the natural course of the migraine attack.The objective of the current analysis is to explore the relationship between treatment efficacy and CNS AEs in patients receiving eletriptan and to determine if certain CNS AEs are more common in responders vs. non-responders.
Priapulida, Sipuncula, Echiura, Pogonophora,And Entoprocta
Authors: Knight-Jones E W , Ryland J S
Published: November 2023

Unsegmented worms with a chitinous cuticle, small surface spines and papillae, a large body cavity and near-radial symmetry, except for paired gonads and nephridia, and a nerve cord regarded as ventral. The anterior body forms an introvert, in which the mouth is central. This is alternately pushed out and withdrawn to burrow, and prey is drawn in and swallowed during withdrawal, having been caught by curved teeth on the everted mouth and pharynx lining. The gut is simple and the anus terminal, except that a few genera have long tails arising ventrally to the anus. These bear many vesicular branches, which contain extensions of the coelom and are thought to be respiratory. Sexes are separate and cleavage·radial, producing loricate larvae which stay in the adult environment.
Sumnlaary and Overview
Authors: Roe Derek
Published: November 2023

This conclusion to the volume should have come from the hand of Glynn Isaac himself, after consultation with all his colleagues in the project. It should be full of the breadth of vision that he brought to the archaeology of the early Palaeolithic, and indeed to all his writing; it should be in his characteristic style; and it should have been written several years ago, at about the time when he would have been a youthful fifty. Though there are many sites and completed research projects, books, and papers, for which Glynn will be permanently remembered, publication of the archaeological work at Koobi Fora should have been a special jewel in his crown— maybe even the greatest, whatever might have followed if he had lived a life of full length. I have written else where (1989) an appreciation of Glynn, who was a close friend and once a fellow-student, and I will not repeat here my own or others’ assessment of his great and enduring contribution to the study of human origins and early development. It is an honour to be asked to fill this particular part of the great gap his passing has left.
Taxonomy and origins
Authors: Corbet G B
Published: November 2023

The European rabbit, Oryctolagus cuniculus, must be one of the most familiar and best known of all mammalian species, both as a wild animal and in its domesticated forms. It has been studied as a resource, as a pest, and as a tool in medical research; it is kept as a family pet and has a firm place in popular folklore. The resultant literature is enormous-so much so that the very volume of information is liable to get in the way of understanding the rabbit as a species.
The Biology of Millipedes
Authors: Hopkin Stephen p. , Read Helen J
Published: November 2023

Millipedes are common components of the leaf-litter fauna of most terrestrial environments. The Biology of Millipedes is the first single-volume review of this important group and covers their ecology, behaviour, physiology, and evolution. This book is essential reading for terrestrial ecologists, zoologists, and students taking courses in invertebrate biology. Introductory chapters consider millipede taxonomy and phylogeny, basic anatomy, locomotion, and ecomorphology. Later chapters review feeding and digestion, metabolism, nerves, and neurosecretion, together with all aspects of millipedes in decomposition processes, and their role as pests. The authors provide an extremely comprehensive bibliography of research papers and literature.
The Photosynthetic Apparatus As A Phyletic Character
Authors: Raven John A , Johnston Andrew M , bin Surif Misni
Published: November 2023

The characteristics of the photosynthetic apparatus (other than the chemistry of the pigments which is dealt with elsewhere in this Symposium) are considered under three headings. In each case comparisons are made both within the chromophytes, and between chromophytes and other major groups.