Citation: Chun-Jing Liu, Dinah Dutta, Lester Mitscher. Synthesis of new penicillin derivatives as drug-like molecules for biological screening[J]. Chinese Chemical Letters, ;2015, 26(1): 113-117. doi: 10.1016/j.cclet.2014.09.008 shu

Synthesis of new penicillin derivatives as drug-like molecules for biological screening

1.
a Higuchi Biosciences Center, The University of Kansas, Lawrence KS66045, USA;
2.
b Department of Medicinal Chemistry, The University of Kansas, Lawrence KS66045, USA

Corresponding author: Chun-Jing Liu,
Received Date: 22 May 2014
Available Online: 22 August 2014

Chemical modification of penicillin β-lactam ring was made. Six thiazolidine amides were produced through N4-C7 β-lactam ring opening of penicillin V methyl ester with various aliphatic, aromatic, and heterocyclic primary amines. Five 8-hydroxypenillic acid derivatives with side chains of methyl, propyl, benzyl, and diethylaminoethyl groups were yielded via β-lactam ring rearrangement from 6-aminopenicillanic acid (6-APA). Parallel synthetic methods were used for the alkylation of 8-hydroxypenillic acid and β-lactam ring opening of penicillin V methyl ester. The biological activities of the compounds were evaluated.
- Penicillin,
- Rearrangement,
- β-Lactam antibiotics,
- Nucleophilic ring opening
1. [1]
  [1] K.B. Hoten, E.M. Onusko, Appropriate prescribing of oral β-lactam antibiotics, Am. Fam. Physician 62 (2000) 611-620.
2. [2]
  [2] G. Lukacs, Recent Progress in the Chemical Synthesis of Antibiotics and Related Microbial Products, vol. 2, Springer, Berlin, 1993p. 621.
3. [3]
  [3] G. Veinberg, M. Vorona, M. Shestakova, I. Kanepe, E. Lukevics, Design of β-lactams with mechanism based nonantibacterial activities, Curr. Med. Chem. 10 (2003) 1741-1757.
4. [4]
  [4] R.R. Gupta, Topics in Heterocyclic Chemistry, Springer, Berlin/Heidelberg, 2010p. 394.
5. [5]
  [5] J.D. Rothstein, S. Patel, M.R. Regan, et al., b-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression, Nature 433 (2005) 73-77.
6. [6]
  [6] P.G. Sammes, Recent chemistry of the β-lactam antibiotics, Chem. Rev. 76 (1976) 113-155.
7. [7]
  [7] A.K. Mukerjee, A.K. Singh, b-Lactams: retrospect and prospect, Tetrahedron 34 (1978) 1731-1767.
8. [8]
  [8] G.H. Hakimelahi, K.S. Shia, C. Xue, et al., Design, synthesis, and biological evaluation of a series of β-lactam-based prodrugs, Bioorg, Med. Chem. 10 (2002) 3489- 3498.
9. [9]
  [9] T.L. Gilchrist, Heterocyclic Chemistry, 2nd ed., Longman Press, Harlow, 1997.
10. [10]
  [10] S. Wolfe, S. Ro, C.K. Kim, Z. Shi, Synthesis and decarboxylation of Δ²-cephem-4 4- dicarboxylic acids, Can. J. Chem. 79 (2001) 1238-1258.
11. [11]
  [11] B. Alcaide, P. Almendros, C. Aragoncillo, b-Lactams: versatile building blocks for the stereoselective synthesis of non β-lactam products, Chem. Rev. 107 (2007) 4437-4492.
12. [12]
  [12] B. Alcaide, P. Almendros, G. Cabrero, M.P. Ruiz, Stereoselective cyanation of 4- formyl and 4-imino-b-lactams: application to the synthesis of polyfunctionalized γ-lactams, Tetrahedron 68 (2012) 10761-10768.
13. [13]
  [13] B. Alcaide, P. Almendros, A. Luna, et al., Controlled rearrangement of lactamtethered allenols with brominating reagents: a combined experimental and theoretical study on alpha-versus β-keto lactam formation, Chem. Eur. J. 17 (2011) 11559-11566.
14. [14]
  [14] S. Dekeukeleire, M. D'hooghe, N. De Kimpe, Diastereoselective synthesis of bicyclic gamma-lactams via ring expansion of monocydic β-lactams, J. Org. Chem. 74 (2009) 1644-1649.
15. [15]
  [15] W. Van Brabandt, N. De Kimpe, Electrophile-induced ring expansions of β-lactams toward γ-lactams, J. Org. Chem. 70 (2005) 8717-8722.
16. [16]
  [16] A.K. Mukerjee, A.K. Singh, Reactions of natural and synthetic β-lactams, Synthesis- Stuttgart 9 (1975) 547-589.
17. [17]
  [17] D.A. Johnson, G.A. Hardcastle Jr., Reaction of 6-aminopenicillanic acid with carbon dioxide, J. Am. Chem. Soc. 83 (1961) 3534-3535.
18. [18]
  [18] R.F. Pratt,M. Dryjanski, E.S. Wun, V.M. Marathias, 8-Hydroxypenillic acid from 6- aminopenicillanic acid: a new reaction catalyzed by a class C β-lactamase, J. Am. Chem. Soc. 118 (1996) 8207-8212.
19. [19]
  [19] C.C. Ruddle, T.P. Smyth, Exploring the chemistry of penicillin as a β-lactamasedependent prodrug, Org. Biomol. Chem. 5 (2007) 160-168.
20. [20]
  [20] L. Heinisch, S. Wittmann, T. Stoiber, et al., Highly antibacterial active aminoacyl penicillin conjugates with acylated bis-catecholate siderophores based on secondary diamino acids and related compounds, J. Med. Chem. 45 (2002) 3032- 3040.
21. [21]
  [21] A.F. Casy, A. Lipczynski, 8-Hydroxypenillic acid: NMR characteristics and facile formation from 6-aminopenicillanic acid, J. Pharm. Pharmacol. 46 (1994) 533-534.
22. [22]
  [22] PubChem: https://pubchem.ncbi.nlm.nih.gov. The compound identification (CID) numbers are 24747544 (2a), 24747436 (2b), 24747499 (2c), 24747495 (2d), 24747364 (2e), 24747549 (2f), 25011528 (3), 25011526 (4a), 24747497 (4b), 24747437 (4c), 25011527 (5a), 24789294 (5b).
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沈阳化工大学材料科学与工程学院沈阳 110142