A general approach to the synthesis of a new class of LTD 4 antagonists is presented. The key diarylpropane framework was prepared by Claisen-Schmidt condensation and selective reduction of the enone. Depending on the bridge to the 7-chloroquinaldine moiety, alkylation or Heck coupling methodology was developed. The chiral sulfides were introduced by asymmetric reduction of the diarylpropanone intermediates and subsequent inversion of the chiral center.Since the discovery of the role played by the leukotrienes in asthma and associated inflammatory diseases the search for specific antagonists or inhibitors of this portion of the aracadonic acid cascade has been intensive. 1 An early candidate for the control of asthma was the LTD 4 antagonist MK-0571/MK-0679. 2,3 Elaboration of this original structure has advanced a new class of LTD 4 antagonists with the selection of L-691,698 (1) and L-699,392 (2) as active agents. 4 Here the 3-thiapropionamide side chain has been replaced with an arylethyl group, and in the case of the former, the trans-double bond has been changed to a phenyl quinaldine ether.Our goal was the development of a general approach to this new class of LTD 4 antagonists. 4,5 By incorporating the quinaldine portion of the molecule at the later stages of the synthesis the target became the diarylpropanol 3. A classical synthesis of a 1,3-diarylpropenone is condensation of an acetophenone and a benzaldehyde, the Claisen-Schmidt reaction, producing an enone known as a chalcone; 6 selective 3,4-reduction then provides the 1,3-diarylpropanone (Scheme 1). In the synthesis of 1 and 2 coupling of the 3′-substituted acetophenone 4 with a 2-carboxybenzaldehyde 5 afforded the backbone of 3 X Abstract published in Advance ACS Abstracts, May 1, 1996. (1) (a) Young, R. N.; Guindon, T. R.; Jones, T. R.; Ford-Hutchinson, A. W.; Bellanger, P.; Champion, E.; Charette, L.; DeHaven, R. N.; Denis, D.; Fortin, R.; Frenette, R.; Gauthier, J.-Y.; Gillard, J. W.; Kakushima, M.; Letts, L. G.; Masson, P.; Maycock, A.; McFarlane, C.; Piechuta, H.; Pong, S. S.; Rosenthal, A.; Williams, H.; Zamboni, R.; Yoakim, C.; Rokach, J. Zamboni, R.; Belley, M.; Champion, E.; Charette, L.; Ford-Hutchinson, A. W.; Frenette, R.; Gauthier, J.-Y.; Leger, S.; Masson, P.; McFarlane, C. S.; Piechuta, H.; Rokach, J.; Williams, H.; Young, R. N.; DeHaven, R. N.; Pong, S. S. Can. Jones, T.; Champion, E.; Charette, L.; Dehaven, R.; Ford-Hutchinson, A. W.; Hoogsteen, K.; Lord, A.; Masson, P.; Piechuta, H.; Pong, S. S.; Springer, J. P.; Therien, M.; Zamboni, R.; Young, R. N. J. Med. Chem. 1990, 33, 2841. (b) Zamboni, R.; Belley, M.; Champion, E.; Charette, L.; DeHaven, R.; Frenette, R.; Gauthier, J. Y.; Jones, T. R.; Leger, S.; Masson, P.; McFarlane, C. S.; Metters, K.; Pong, S. S.; Piechuta, H.; Rockach, J.; Therien, M.; Williams, H. W. R.; Young, R. N. J. Med. Chem. 1992, 35, 3832. (3) McNamara, J. M.; Leazer, J. L.; Bhupathy, M.; Amato, J. S.; Reamer, R. A.; Reider, P. J.; Grabowski, E. J. J. J. Org. Chem. 1989, 54, 3718. For the preparation of the ch...
Ph'OTMS NMR spectra of 2c are also consistent with the proposed structure.14 Furthermore, addition of a trace of ptoluenesulfonic acid to 2c resulted in its immediate and quantitative rearrangement to -siloxy ketone 3c.la At 60 °C, in the absence of acid, the rearrangement of 2c to 3c also appeared to be accelerated. -Siloxy epoxide 2c proved to be surprisingly stable when the oxidation was carried out in anhydrous THF (16 h, 25 °C) and was isolated in greater than 90% yield, as an oil, by extraction into n-pentane. -Siloxy epoxides 2b and 2d were also observed by NMR, but were much less stable, rearranging within 1-8 h to -siloxy ketones 3b and 3d, respectively (Table II).Asymmetric oxidation of silyl enol ethers lb and Id at 60 °C by chiral sulfamyloxaziridine (+)-(RJl)-615 gave, after
PurposeTo provide public sector organizations with a development map to achieve employee and customer satisfaction and to align organizational processes for goal achievement.Design/methodology/approachThe paper re‐works the highly influential and widely validated service‐profit chain and presents an analogous model, which reflects the essential differences of public sector organizations.FindingsIt was found that there is a direct link between the achievement of the organizational goal and the organization's ethics and values. This indicates that goal achievement reinforces the legitimacy of the values and ethics as the basis for organizational success.Practical implicationsPresents a practical model and explains, with examples, how an organization might implement this model. Identifies how public organizations can measure their customer value variables.Originality/valueDespite the popularity of the service‐profit chain there has been no model for the public sector. This has been identified as a need in the literature. Therefore, this paper presents a long overdue and much needed public sector model. The model has great value for all levels of governmental bureaucracy irrespective of core business or global location.
PurposeThe purpose of this paper is to highlight the global dearth of training options to support women entrepreneurs and to forward a set of recommendations to better meet the learning needs of women who own their businesses.Design/methodology/approachThe paper provides a thorough literature review on the topic, which examines the learning and training experiences of female entrepreneurs in a wide range of disparate societies.FindingsThe absence of leaning, training and professional development opportunities for women entrepreneurs is found to be an almost universal phenomenon. In the few examples where training has been planned and provided, the results have been very significant. Further, women and their businesses are disadvantaged by the lack of training available and that this comes at a high cost to their businesses.Research limitations/implicationsThe implications are that countries are hindering economic activity, growth and prosperity by ignoring the professional development needs of women business owners.Originality/valueThe topic of professional development opportunities for women entrepreneurs, especially a comprehensive international comparison, appears to be a first in the literature. The value of the piece is that agencies supporting small business and/or women can identify ways in which they can improve service delivery and outcomes.
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