bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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).