Добавил:

Sekretar kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Ростовский Государственный Медицинский Университет

Предмет:

Медицина общая

Файл:

Книга_5872_Библиотеки_им_академика_М_И_Перельмана

.pdf

Скачиваний:

Добавлен:

31.08.2026

Размер:

28 Мб

Скачать

☆

<<< < Предыдущая 1 2 3 4 5 6 7 89 / 419 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

72 Chemistry and Biology of Beta-Lactams

Ph;

CH(Me)Et,

https://t.me/med1917

Xu et al.74 synthesized and examined four isomeric β-lactams for CAI activity. These β-lactams were modied by keeping C3 alkyl substituent of ezetimibe at N1 in the new β-lactam. In addition, β-lactam was tested on high cholesterol, and cholesterol lowering was observed (Figure 2.19).

Carr et al.75 synthesized and investigated structure–activity relationship for some conformationally rigid β-lactams. These molecules were tested for antiproliferative activity against human breast carci- noma cell lines. A β-lactam showed antiproliferative activity in nanomolar range, and it also showed antimitotic effects.

A series of β-lactams were synthesized modifying the C4 substituents followed by the study of O’Boyle

75, 76

et al.

The in vitro antiproliferative screening was conducted against MCF-7 cancer line. The β-lactam

with 4-ethoxyphenyl group at C4 demonstrated excellent activity. Notably, this molecule along with combretastatin A4 led to the arrest of G2/M phase of cell cycle and induced apoptosis. Moreover, the mitotic catastrophe for this β-lactam was demonstrated in breast cancer cells.

The authors77 reported the synthesis of some water-soluble CA4 analogues using β-lactams. They prepared phosphate ester and amino acid amide derivatives. Both series of compounds showed antiproliferative activity. They also induced apoptosis and mitotic catastrophe. Two β-lactams showed the highest potency against MCF-7 cell lines. A biotransformation was necessary for phosphate ester derivative to be medicinally active as they were unable to inhibit in vitro tubulin polymerization. In contrast, amino acid amide derivatives did not require biotransformation.

Wakselman et al.78 carried out studies on functionalized 3,3-diuoro-β-lactams as inhibitors of porcine pancreatic elastase (PPE) and HLE. β-Lactam, a chloro derivative, was found to be effective in preventing elastase-induced degradation of lung elastic bers. The involvement of suicidal-type mechanism was suggested for inactivation of elastins (PPE and HLE).

Guner et al.79 synthesized substituted 3,3-dichloro-β-lactams via Staudinger cycloaddition. These compounds were investigated in vitro for antimicrobial activity against bacterial (S. aureus, B. subtilis,

1 5

H, Me;

MeO

OMe

OMe OMe

OMe

R CHMe

H, Me;

Ph,

CH2OCH

OMe

;

4-OHC

Ph,

OBz

H, Me,

MeO

(CH

OMe

)

OMe

OCH

FIGURE 2.19 Arylated β-lactams.

73Monocyclic Beta-Lactams

OMe,

https://t.me/med1917

H2N

FIGURE 2.20 Differently substituted monocyclic β-lactams.

Cl;

NH.HCl

N H

COO

Bu;

OCOCH

O COCH

OMe,

Me,

;

E. coli, P. aeruginosa) and fungal strains (C. albicans and C. glabrata). These β-lactam derivatives exhibited activity against Gram-negative (especially P. aeruginosa) and fungal strains. Further, changing the substituents does not alter the antimicrobial activities (Figure 2.20).

A series of 3-(3-guanidinopropyl)azetidin-2-ones were prepared and tested for in vitro inhibition of thrombin, tryptase, and plasmin. The N-acylated β-lactams were active inhibitors of thrombin and plasmin in comparison to its N-unsubstituted compound. The C4 substituent is good for inhibitory activity, and the presence of polar groups at C4 enhanced thrombin-to-plasmin selectivity. Moreover, the transisomers were more active than the cis-isomers. A β-lactam with three nitrogens at the C3 site was found to be an inhibitor of serine proteases (thrombin, plasmin, and trypsin).

2.5.1 Some Experimental Conditions for the Synthesis of Monocyclic β-Lactams

Depending on the reactants and the conditions of the experiments, the stereochemistry of the β-lactams may alter.80 A few experimental conditions using modern microwave-induced and classical method for the preparation of monocyclic β-lactams are described here. In particular, focus has been aimed on the diverse conditions for this purpose used in our research group.

2.5.1.1 Experiment and Condition 1

Domestic microwave irradiation of a solution of imine (derived from aniline and benzaldehyde) with acetoxyacetyl chloride in benzene and triethylamine (or N-methylmorpholine (NMM)) produced a mixture of cis- (70%) and trans-β -lactams (30%). The reaction temperature was 50°C. After 5 min of irradiation, it produced a mixture of cis- (70%) and trans-β-lactams (30%). An automated microwave was also used for this purpose successfully.

2.5.1.2 Experiment and Condition 2

The above reaction was repeated using chlorobenzene and NMM at 95–100°C. The reaction was completed within 5–6 min, and it produced a mixture of cis- (5–10%) and trans-isomers (90–95%).

2.5.1.3 Experiment and Condition 3

The same reaction between the imine and acid chloride was conducted in a microwave oven at the temperature range of 95–100°C in the presence of NMM without using any solvent. The reaction was completed within 3 min, and it produced a mixture of cis- (5–10%) and trans-isomers (90–95%).

74 Chemistry and Biology of Beta-Lactams

https://t.me/med1917

2.5.1.4 Experiment and Condition 4

The reaction of the Schiff base with acid chloride in chlorobenzene/NMM was conducted using a preheated oil bath (90°C). The reaction was completed within 5 min. An identical result as given in experiment number 3 was observed.

2.5.1.5 Experiment and Condition 5

An oil bath was used, but the temperature was increased from room temperature to 90°C. The same reaction was completed within 15 min, and the isomer ratio was cis- (50%) and trans- (50 %).

2.5.1.6 Experiment and Condition 6

The aldehyde and amine, clay (montmorillonite and bentonite), NMM, AcOCH2COCl, and chlorobenzene were mixed. It was irradiated in a microwave for 2 min, but trans-isomer of the β-lactam (80%) was the major product.

2.5.1.7 Experiment and Condition 7

The reaction of the Schiff base with acid chloride in the presence of triethylamine (or NMM) in dichloromethene at zero degree to room temperature afforded the cis-isomer.

2.6 Conclusion

Research on β-lactams has been growing rapidly because of their novelty in structures, variation of their substituents, stereochemical features, and above all medicinal values. Many examples of monocyclic β-lactams have been provided mentioning their selective and diverse medicinal properties. The medicinal activities heavily depend on the conguration and the groups present in β-lactams. The diversity and functional groups’ tolerance as shown in the examples should guide researchers in the selection of suitable substrates in their future aims.

Acknowledgments

AD is grateful to CEA-Grenoble, Joseph Fourier University, University of Göttingen, and University of California, Los Angeles, for their support. BKB is grateful to the US NIH, the US NCI, Texas Kleberg Foundation, Stevens Institute of Technology, University of Texas MD Anderson Cancer Center, University of Texas-Pan American, University of Texas Health Science Center (San Antonio), and Community Health Systems of Texas for their competitive nancial and moral support to his research. AD and BKB acknowledge support from their current employer, Prince Mohammad Bin Fahd University. BKB is also grateful to Dr. Aman Bhalla for useful discussions.

REFERENCES

1. Balaban, A. T.; Oniciu, D. C.; Katritzky, A. R. Chem. Rev. 2004, 104, 2777–2812.

2. (a) Dolle, R. E.; Nelson, K. H. J. Comb. Chem. 1999, 1, 235–282. (b) Franzen, R. G. J. Comb. Chem .

2000, 2, 195–214. (c) Dolle, R. E. J. Comb. Chem. 2001, 3, 477–517. (d) Hanessian, S.; McNaughtonSmith, G.; Lombart, H. G.; Lubell, W. D. Tetrahedron 1997, 53, 12789–12854.

3. Fleming, A. Br. J. Exp. Pathol. 1929, 10, 226 –236.

4. (a) Holden, K. G.; Morin, R. B.; Gorman, M. (Eds.), In Chemistry and Biology of β-lactam antibiotics,

vol. 2, Academic, London, 1982, p. 114. (b) Mata, E. G.; Fraga, M. A.; Delpiccolo, C. M. L. J. Comb. Chem. 2003, 5, 208–210. (c) Pawar, R. P.; Andurkar, N. M.; Vibhute, Y. B. J. Indian Chem. Soc. 1999,

75Monocyclic Beta-Lactams

https://t.me/med1917

76, 271. (d) Gootz, T. D. Clin. microbiol. Rev. 1990, 13–31. (e) Samarendra N. Maiti, Top. Heterocycl. Chem. 2006, 2, 207–246. (f) Singh, G. S. Mini-Rev. Med. Chem. 2004, 4, 69. (g) Singh, G. S. Mini-Rev. Med. Chem. 2004, 4, 93. (h) Risi, C. D.; Pollini, G. P.; Veronese, A. C.; Bertolasi, V. Tetrahedron Lett.

1999, 4, 6995. (i) Georg, G. I. (Ed.), In The Organic Chemistry of β-Lactams, VCH, New York, 1993. (j) Abdulla, R. F.; Fuhr, K. H. J. Med. Chem. 1975, 18, 625–627. (k) Durckheimer, W.; Blumbach, J.; Lattrell, R.; Scheunemann, K. H. Angew. Chem. Int. Ed. Engl . 1985, 24, 180 –202 .

5. (a) Arya, N.; Jagdale, A. Y.; Patil, T. A.; Yeramwar, S. S.; Holikatti, S. S.; Dwivedi, J.; Shishoo, C. J.;

Jain, K. S. Eur. J. Med. Chem. 2 014, 74, 619–656. (b) Kamath, A.; Ojima, I. Tetrahedron 2012, 68, 10640–10664. (c) Mehta, P. D.; Sengar, N. P. S.; Pathak, A. K. Eur. J. Med. Chem. 2010, 45, 5541–5560.

6. (a) Ojima, I. Acc. Chem. Res. 1995, 28, 383–389. (b) Ojima, I.; Delaloge, F. Chem. Soc. Rev. 1997, 26,

377–386. (c) Deshmukh, A. R.; Bhawal, B. M.; Krishnaswamy, D.; Govande, V. V.; Shinkre, B. A.; Jayanthi, A. Curr. Med. Chem. 2004, 11, 1889–1920. (d) Alcaide, B.; Almendros, P. Curr. Med. Chem.

2004, 11, 1921–1949. (e) Palomo, C.; Aizpurua, J. M.; Ganboa, I.; Oiardide, M. Curr. Med. Chem. 2004, 11, 1837–1872 .

7. (a) Gorden, E. M.; Ondetti, M. A.; Plusec, J.; Cimarusti, C. M.; Bonner, D. P.; Sykes, R. B. J. Am. Chem.

Soc. 1982, 6053. (b) Banik, B. K.; Becker, F. F.; Banik, I. Bioorg. Med. Chem. 2004, 12, 2523. (c)

Slusarchyk, W. A.; Balton, S. A.; Huang, M. H. J. Med. Chem. 2003, 46, 12.

8. Singh, G. S.; Sudheesh, S. Arkivoc. 2014, (i), 337–385.

9. Turos, E.; Long, T. E.; Heldreth, B.; Leslie, J. M.; Reddy, G. S. K.; Wang, Y.; Coates, C.; Konaklieva, M.;

Dickey, S.; Lim, D. V.; Alonsoc, E.; Gonzalez, J. Bioorg. Med. Chem. Lett. 2006, 16, 2084–2090.

10. O’Driscoll, M.; Greenhalgh, K.; Young, A.; Turos, E.; Dickey, S.; Lim, D. V.; Turos, E. Bioorg. Med.

Chem. 2008, 16, 7832–7837.

11. Cervellati, R.; Galletti, P.; Greco, E.; Cocuzza, C. E. A.; Musumeci, R.; Bardini, L.; Paolucci, F.; Pori,

M.; Soldati, R.; Giacomini, D. Eur. J. Med. Chem. 2013, 60, 340–349.

12. Bhat, I. K.; Chaithanya, S. K.; Satyanarayana, P. D.; Kalluraya, B. J. Serb. Chem. Soc. 2007, 72, 437–442.

13. Bagherwal, A.; Baldi, A.; Nagar, R. K.; Patidar, D. K. Int. J. ChemTech Res. 2011, 3, 274–279.

14. Rokade, Y.; Dongare, N. Res. J. Chem. 2010, 3, 641–645.

15. Gawande, S. K.; Khadsan, R. E. Int. J. Pharm. Sci. Res. 2014, 5, 2966 –2971.

16. Patel, R.; Mangal, A.; Engla, G.; Bhadoriya, S.; J. Pharm. Res. 2012, 5, 2159–2161.

17. Iiango, K.; Arunkumar, S. Tropical J. Pharmaceutical Res. 2011, 10, 219 –229.

18. Halve, A. K.; Bhadauria, D.; Dubay, R. Bioorg. Med. Chem. Lett. 2007, 17, 341–345.

19. Cao, X. F.; Wang, Y. S.; Li, S. W.; Chen, C. S.; Ke, S.-Y. J. Chin. Chem. Soc. 2011, 58, 1–6.

20. Swamy, P. V.; Chandrasekhar, K. B.; Kambhampati, P. C. Der Pharma Chem. 2015, 7, 338–345.

21. Shah, S. K.; Dorn, Jr. C. P.; Finke, P. E.; Hale, J. J.; Hagmann, W. K.; Brause, K. A.; Chandler, G. O.;

Kissinger, A. L.; Ashe, B. M.; Weston, H.; Knight, W. B.; Maycock, A. L.; Dellea, P. S.; Fletcher, D. S.; Hand, K. M.; Mumford, R. A.; Underwood, D. J.; Doherty, J. B. J. Med. Chem. 1992, 35, 3745–3754.

22. Green, B. G.; Chabin, R.; Mills, S.; Underwood, D. J.; Shah, S. K.; Kuo, D.; Gale, P.; Maycock, A. L.;

Liesch, J.; Burgey, C. S.; Doherty, J. B.; Dorn, C. P.; Finke, P. E.; Hagmann, W. K.; Hale, J. J.; Maccoss, M.; Westler, W. M.; Knight, W. B. Biochemistry 1995, 34, 14331–14343.

23. Borthwick, A. D.; Weingarten, G.; Haley, T. M.; Tomaszewski, M.; Wang, W.; Hu, Z.; Bedard, J.; Jin, H.;

Yuen, L.; Mansour, T. S. Bioorg. Med. Chem. Lett. 1998, 8, 365–370.

24. Finke, P. E.; Shah, S. K.; Fletcher, D. S.; Ashe, B. M.; Brause, K. A.; Chandler, G. O.; Dellea, P. S.; Hand,

K. M.; Maycock, A. L.; Osinga, D. G.; Underwood, D. J.; Weston, H.; Davis, P.; Doherty, J. B. J. Med. Chem. 1995, 38, 2449–2462.

25. (a) Deziel, R.; Malenfant, E. Bioorg. Med. Chem. Lett. 1998, 8, 1437–1442; (b) McKittrick, B. A.; Ma,

K.; Huie, K.; Yumibe, N.; Davis, Jr. H.; Clader, J. W.; Czarniecki, M.; McPhail, A. T. J. Med. Chem. 1998, 41, 752 –759.

26. Veinberg, G.; Vorona, M.; Musel, D.; Bokaldere, R.; Shestakova, I.; Kanepe, I.; Lukevics, E. Chem. of

Heterocyclic Comp. 2004, 40, 816–822.

27. Kostova, M. B.; Myers, C. J.; Beck, T. N.; Plotkin, B. J.; Green, J. M.; Boshoff, H. I. M.; Barry III, C. E.;

Deschamps, J. R.; Konaklieva, M. I. Bioorg. Med. Chem. 2011, 19, 6842–6852.

28. Clemente, A.; Domingos, A.; Grancho, A. P.; Iley, J.; Moreira, R.; Neres, J.; Palma, N.; Santana, A. B.;

Valente, E. Bioorg. Med. Chem. Lett. 20 01, 11, 1065–1068.

29. Beck, T. N.; Lloyd, D.; Kuskovsky, R.; Minah, J.; Arora, K.; Plotkin, B. J.; Green, J. M.; Boshoff, H. I.;

Barry III, C.; Deschamps, J.; Konaklieva, M. I. Bioorg. Med. Chem. 2015, 23, 632– 647.

76 Chemistry and Biology of Beta-Lactams

https://t.me/med1917

30. Galletti, P.; Soldati, R.; Pori, M.; Durso, M.; Tolomelli, A.; Gentilucci, L.; Dattoli, S. D.; Baiula, M.;

Spampinato, S.; Giacomini, D. Eur. J. Med. Chem. 2014, 83, 284 –293.

31. Aoyama, Y.; Uenaka, M.; Kii, M.; Tanaka, M.; Konoike, T.; Hayasaki-Kajiwara, Y.; Naya, N.; Nakajima,

M. Bioorg. Med. Chem. 2001, 9, 3065–3075.

32. Gerona-Navarro, G.; deVega, M. J. P.; Garcia-Lopez, M. T.; Andrei, G.; Snoeck, R.; Balzarini, J.; Clercq,

E. D.; Gonzalez-Muniz, R. Bioorg. Med. Chem. Lett. 2004, 14, 2253–2256.

33. Feledziak, M.; Michaux, C.; Lambert, D. M.; Marchand-Brynaert, J. Eur. J. Med. Chem. 2013, 60,

101–111.

34. Adlington, R. M.; Baldwin, J. E.; Becker, G. W.; Chen, B.; Cheng, L.; Cooper, S. L.; Hermann, R. B.;

Howe, T. J.; McCoull, W.; McNulty, A. M.; Neubauer, B. L.; Pritchard, G. J. J. Med. Chem. 2001, 44, 1491–15 08.

35. Burnett, D. A.; Caplen, M. A.; Davis, Jr. H. R.; Burrier, R. E.; Clader, J. W. J. Med. Chem. 1994, 37,

1733–1736 .

36. Clader, J. W.; Burnett, D. A.; Caplen, M. A.; Domalski, M. S.; Dugar, S.; Vaccaro, W.; Sher, R.; Browne,

M. E.; Zhao, H.; Burrier, R. E.; Salisbury, B.; Davis, Jr. H. R. J. Med. Chem. 1996, 39, 3684–3693.

37. Vaccaro, W. D.; Sher, R.; Davis, Jr. H. R. Bioorg. Med. Chem. Lett. 1998, 8, 319 –322.

38. Rosenblum, S. B.; Huynh, T.; Afonso, A.; Davis, Jr. H. R. Tetrahedron 2000, 56, 5735–5742.

39. Heek, M. V.; France, C. F.; Compton, D. S.; Mcleod, R. L.; Yumibe, N. P.; Alton, K. B.; Sybertz, E. J.;

Davis, Jr. H. R. J. Pharmacol. Exp. T her. 1997, 283, 157–163.

40. Rosenblum, S. B.; Huynh, T.; Afonso, A.; Davis, Jr. H. R.; Yumibe, N.; Clader, J. W.; Burnett, D. A. J.

Med. Chem. 1998, 41, 973–980.

41. Vaccaro, W. D.; Sher, R.; Davis, Jr. H. R. Bioorg. Med. Chem. 1998, 6, 1429–1437.

42. Burnett, D. A.; Caplen, M. A.; Domalski, M. S.; Browne, M. E.; Davis, Jr. H. R.; Clader, J. W. Bioorg.

Med. Chem . Lett. 2002, 12, 311–314.

43. Liu, Y.; Chen, J.-L.; Wang, G.-H.; Sun, P.; Huang, H.; Qing, F.-L. Tetrahedron Lett. 2013, 54, 5541–5543.

44. McKittrick, B. A.; Ma, K.; Dugar, S.; Clader, J. W.; Davis, Jr. H. R.; Czarniecki, M. Bioorg. Med. Chem.

Lett. 1996, 6, 1947–1950.

45. Kirkup, M. P.; Rizvi, R.; Shankar, B. B.; Dugar, S.; Clader, J. W.; McCombie, S. W.; Lin, S. –I.; Yumibe,

N.; Huie, K.; Heek, M. V.; Compton, D. S. Bioorg. Med. Chem. Lett. 1996, 6, 2069–2072.

46. Dugar, S.; Yumibe, N.; Clader, J. W.; Vizziano, M.; Huie, K.; Heek, M. V.; Compton, D. S.; Davis, Jr. H.

R. Bioorg. Med. Chem. Lett. 1996, 6, 1271–1274.

47. Wang, Y.; Zhang, H.; Huang, W.; Kong, J.; Zhou, J.; Zhang, B. Eur. J. Med. Chem. 2009, 44, 1638 .

48. Banik, B. K.; Banik, I.; Becker, F. F. Bioorg. Med. Chem. 2005, 13, 3611–3622.

49. Banik, B. K.; Banik, I.; Becker, F. F. Eur. J. Med. Chem. 2 010, 45, 846–848.

50. Sun, L.; Vasilevich, N. I.; Fuselier, J. A.; Hocart, S. J.; Coy, D. H. Bioorg. Med. Chem. Lett. 2004, 14,

2041–2046.

51. Tripodi, F.; Pagliarin, R.; Fumagalli, G.; Bigi, A.; Fusi, P.; Orsini, F.; Frattini, M.; Coccetti, P. J. Med.

Chem. 2012, 55, 2112 –2124.

52. Jarrahpour, A.; Ebrahimi, E.; Sinou, V.; Latour, C.; Brunel, J. M. Eur. J. Med. Chem. 2014, 87, 364–371.

53. Zhou, N. E.; Guo, D.; Thomas, G.; Reddy, A. V. N.; Kaleta, J.; Purisima, E.; Menard, R.; Micetich, R.

G.; Singh, R. Bioorg. Med. Chem. Lett. 2003, 13, 139 –141.

54. Setti, E. L.; Davis, D.; Chung, T.; McCarter, J. Bioorg. Med. Chem. Lett. 2003, 13, 2051–2053.

55. Woulfe, S. R.; Miller, M. J. J. Med. Chem. 1985, 28, 1447–1453.

56. Nuzzi, A.; Fiasella, A.; Ortega, J. A.; Pagliuca, C.; Ponzano, S.; Pizzirani, D.; Bertozi, S. M.; Ottonello,

G.; Tarozzo, G.; Reggianni, A.; Bandiera, T.; Bertozzi, F.; Piomelli, D. Eur. J. Med. Chem. 2016, 111, 138 –159.

57. Jarrahpour, A. A.; Shekarriz, M.; Taslimi, A. Molecules 2004, 9, 939–948.

58. Drazic, T.; Molcanov, K.; Sachdev, V.; Malnar, M.; Hecimovic, S.; Patankar, J. V.; Obrowsky, S.; Levak-

Frank, S.; Habus, I.; Kratky, D. Eur. J. Med. Chem. 2014, 87, 722–734.

59. Mckee, J. A.; Sharma, S. K.; Miller, M. J. Bioconjugate Chem. 1991, 2, 281–291.

60. Dolence, E. K.; Minnick, A. A.; Lin, C.; Miller, M. J. J. Med. Chem. 1991, 34, 968–978.

61. Broccolo, F.; Cainelli, G.; Caltabiano, G.; Cocuzza, C. E. A.; Fortuna, C. G.; Galletti, P.; Giacomini, D.;

Musumarra, G.; Musumeci, R.; Quintavalla, A. J. Med. Chem. 2006, 49, 2804–2811.

62. Cainelli, G.; Galletti, P.; Garbisa, S.; Giacomoni, D.; Sartor, L.; Quintavalla, A. Bioorg. Med. Chem.

2003, 11, 5391–5399.

77Monocyclic Beta-Lactams

https://t.me/med1917

63. Cainelli, G.; Galletti, P.; Garbisa, S.; Giacomini, D.; Sartor, L.; Quintavalla, A. Bioorg. Med. Chem.

2005, 13, 6120 – 6132 .

64. Harsha, Y. P.; Wadher, S. J.; Dilip, K. J. J. Pharm. Sci. Innov. 2012, 1, 44–46.

65. Junne, S. B.; Kadam, A. B.; Zangade, S. B.; Shinde, S. L.; Vibhute, Y. B. Int. Multidiscip. Res. J. 2012,

2, 4 4 – 47.

66. Chhajed, S. S.; Manisha, P.; Bastikar, V. A.; Animeshchandra, H.; Ingle, V. N.; Upasani, C. D.; Wazalwar,

S. S. Bioorg. Med. Chem. Lett. 2010, 20, 3640–3644.

67. Subudhi, B. B.; Ghosh, G. Bull. Chem. Soc. Ethiop. 2012, 26, 455–46 0.

68. Pawar, P. Y.; Kalure, S. U.; Kulkarni, R. B. Int. J. Pharm . Pharmaceu. Sci. 2012, 4, 464–467.

69. Chimento, A.; Sala, M.; Gomez-Monterrey, I. M.; Musella, S.; Bertamino, A.; Caruso, A.; Sinicropi,

M. S.; Sirianni, R.; Puoci, F.; Parisi, O. I.; Campana, C.; Martire, E.; Novellino, E.; Saturnino, C.; Campiglia, P.; Pezzi, V. Bioorg. Med. Chem. Lett. 2013, 23, 6401–6405.

70. Veinberg, G.; Bokaldere, R.; Dikovskaya, K.; Vorona, M.; Kanepe, I, Shestakova, I.; Yashchenko, E.;

Lukevics, E. Chem. Heterocycl. Compd. 2003, 39, 587–593.

71. Sugumaran, M.; Sethuvani, S.; Poornina, M. Res. J. Pharm. Biol. Clin. Sci. 2012, 3, 625– 631.

72. Gowri, M.; Beaula, W. S.; Biswal, J.; Dhamodharan, P.; Saiharish, R.; Prasad, S. R.; Pitani, R.;

Kandaswami, D.; Raghunathan, R.; Jeyakanthan, J.; Rayala, S. K.; Venkatraman, G. Biochim. et Biophys. Acta 2016, 1860, 6 36 –6 47.

73. Singh, G. S.; Mbukwa, E.; Pheko, T. Arkivoc. 2007, (ix), 80–90.

74. Xu, X.; Fu, R.; Chen, J.; Chen, S.; Bai, X. Bioorg. Med. Chem. Lett. 2007, 17, 101–104.

75. Carr, M.; Greene, L. M.; Knox, A. J. S.; Lloyd, D. G.; Zisterer, D. M.; Meegan, M. J. Eur. J. Med. Chem.

2010, 45, 5752–5766.

76. O”Boyle, N. M.; Carr, M.; Greene, L. M.; Keely, N. O.; Knox, A. J. S.; McCabe, T.; Zisterer, D. M.;

Meegan, M. J. Eur. J. Med. Chem. 2011, 46, 4 595– 4607.

77. O’Boyle, N. M.; Greene, L. M.; Keely, N. O.; Wang, S.; Cotter, T. S.; Zisterer, D. M.; Meegan, M. J. Eur.

J. Med. Chem. 2013, 62, 705–721.

78. Wakselman, M.; Joyeau, R.; Kobuiter, R.; Boggettto, N.; Vergely, I.; Maillard, J.; Okochi, V.; Montagne,

J.-J. Reboud-Ravaux, M. Fed. Eur. Biochem. Soc. 1991, 282, 377–381.

79. Guner, V.; Yildirir, S.; Ozcelik, B. IL Farmaco. 2000, 55, 150.

80. (a) Banik, B. K.; Ed. Heterocyclic Scaffolds I. Top. Heterocycl. Chem., Springer. 2010, 22, 1–379; (b)

Banik, B. K. Ed, Top. Heterocycl. Chem., Springer. 2012, 30, 12–26; (c) Banik, B. K. Beta Lactams: Novel Synthetic Pathways and Applications. Ed. Springer, 2017, 141–149.

https://t.me/med1917

Polycyclic Beta-Lactams: Synthesis

by Diverse Methods

Aparna Das1 and Bimal Krishna Banik

Department of Mathematics and Natural Sciences, College of Sciences and Human Studies,

Prince Mohammad Bin Fahd University, Al Khobar 31952, Kingdom of Saudi Arabia.

Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Deanship of Research Development, Prince Mohammad Bin Fahd University, Al Khobar 31952, Kingdom of Saudi Arabia. *Corresponding authors: Aparna Das, email: aparnadasam @gmail .c om; BimalKrishna Banik, email: bimalbanik10 @gmail .c om; bbanik @pmu .edu .sa

3.1 Introduction

Penicillin and cephalosporins1 were the naturally occurring β-lactam antibiotics up to 1970. The discovery of 7-α-methoxycephalosporins2 in 1971 helped to initiate research on new antibiotics. The β-lactam antibiotics are classied into several groups based on their structures (Figure 3.1).

• Penicillin

• Cephalosporin (penam)

• Cephamycin (cephem)

• Oxacephem

• Monobactam

Carbacephems3 are cephalosporins and are used as antibiotics. Loracarbef (lorabid) is a clinically active antibiotic (Figure 3.2).

Tricyclic antibiotics of this group are called trinems4 (Figure 3.3). GV 104326 is a tribactam antibiotic. The antibiotic activity of β-lactams and the antiviral property of nucleosides were merged together

to afford dual properties in a molecule.5 Ugi et al.6 reported a β-lactam in which steroidal and β-lactam units were fused (Figure 3.4).

Interestingly, β-lactams demonstrated cholesterol absorption inhibition7 and human leukocyte elastase

(HLE) properties.

• Penem

• Oxapenams

• Carbapenems

• Nocardicin

3.2 Methods for the Preparation of the β-Lactams

Many methods are available to prepare β-lactams, and some crucial methods are discussed in this chapter.

3.2.1 Synthesis of β-Lactams by the Formation of the N1–C2 Bond

Synthesis of azetidinones was conducted through dehydration of β-amino acids. This procedure was used for the synthesis of penicillin by Sheehan et al. (Scheme 3.1).

DOI: 10.1201/9780367816339-3

FIGURE 3.1 A few important and cr ucial β-lactam antibiotics.

CONHPh

Lorabid

GV 104326 (tribactam)

CONHMe

https://t.me/med1917

79Polycyclic Beta-Lactams

FIGURE 3.2 Important medicine, Lorabid.

FIGURE 3.3 Tr ib acta m.

()

FIGURE 3.4 β-Lactams Conjugated with Steroids.

COOH

OMe

CONHR

80 Chemistry and Biology of Beta-Lactams

H H

CO2Et

https://t.me/med1917

CO2CH2Ph

COOEt

NPh

COOEt

-BuOH

CNH

HO2C

SCHEME 3.1 Dehydration of β-Amino Acids to β-Lactams.

SCHEME 3.2 Synthesis of β-Lactams by Photochemistry.

SCHEME 3.3 Synthesis of β-Lactams from Malonates.

Ph3CNH

CO2CH

CO2Et

NPh

A few scientists used triphenylphosphine-pyridine disulde and methanesulfonyl chloride to form the

amide structure present in 2-azetidinones from β-amino acids.

3.2.2 Synthesis of β-Lactams by the Formation of the C2–C3 Bond

The C2–C3 (carbon–carbon) bond formation method for the synthesis of 2-azetidinones is complicated. Maruyama et al. used a photochemical method to prepare 4-keto-β-lactam (Scheme 3.2).

3.2.3 Synthesis of β-Lactams by the Formation of the C3–C4 Bond

This method required creating a nucleophilic center at C3 and an electrophilic part at C4 or vice versa. Sheehan et al. synthesized 2-azetidinone by an intramolecular nucleophilic reaction using malonate anions and halides (Scheme 3.3).

11, 12

3.2.4 Synthesis of β-Lactams by the Formation of the C4–N1 Bond

This procedure proceeded through an SN2 displacement reaction of a leaving group connected to the β-carbon amide by intramolecular amide nitrogen in basic media. Miller synthesized β-lactams by the cyclization of β-hydroxy amides (Scheme 3.4).

3.2.5 Synthesis of β-Lactams: Multiple Bond-Forming Reactions

3.2.5.1 Alkene-Isocyanate Cycloaddition Method

Chlorosulfonyl isocyanate reacted with olens to form β-lactams.14 Colvin et al. demonstrated the reaction of chlorosulfonyl isocyanate with numerous allyl and allenyl silanes to give substituted β-lactams.15 These were converted into 3-unsubstituted NH-β-lactams by removing the chlorosulfonyl moiety and silyl deprotection (Scheme 3.5).

Chmielewski et al. employed cycloaddition between tosyl isocyanate and sugar-derived vinyl ethers to

obtain β-lactams (Scheme 3.6).

NHR'

SCHEME 3.4 Synthesis of β-Lactams from β-Hydroxy Amides.

CH2SiMe2Ph

50%

H H

Alkyl

https://t.me/med1917

81Polycyclic Beta-Lactams

SiMe2Ph

CSI, CCl

ii. aq. Na2SO

Me3Si

SCHEME 3.5 Synthesis of 3-Unsubstituted NH-β-Lactams.

SCHEME 3.6 Synthesis of β-Lactams from Sugars.

NTs

SCHEME 3.7 Synthesis of β-Lactams from Spirocyclopropane.

CH2SiMe

Suga

NTs

SCHEME 3.8 Synthesis of β-Lactams by Carbenoid Insertion.

SCHEME 3.9 Synthesis of β-Lactams from Carbenes.

Cordero et al. showed a ring contraction of spirocyclopropane isoxazolidine to yield β-lactams

(Scheme 3.7).

Wing et al. reported a Ru-catalyzed intramolecular carbenoid C–H insertion for the preparation of

β-lactam in more than 99% cis-stereoselectivity (Scheme 3.8).

Rigby et al. showed β-lactam ring formation by a reaction between dimethoxycarbene with isocya-

nates (Scheme 3.9).

[RuCl

(p-cymen)]

OCH

Chlorobenzene

C O

2H5

2H5O2

NOR

CO OCH

OCH

<<< < Предыдущая 1 2 3 4 5 6 7 89 / 419 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > Следующая >>>

Соседние файлы в папке Библиотека им академика М.И. Перельмана

#
31.08.202634 Мб0Книга_5867_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202632 Мб0Книга_5868_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202630 Мб0Книга_5869_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202629 Мб0Книга_5870_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202629 Мб0Книга_5871_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202628 Мб0Книга_5872_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202627 Мб0Книга_5873_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202627 Мб0Книга_5874_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202627 Мб0Книга_5875_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202625 Мб0Книга_5876_Библиотеки_им_академика_М_И_Перельмана.pdf
#
31.08.202624 Мб0Книга_5877_Библиотеки_им_академика_М_И_Перельмана.pdf