Login Register Cart 0
Generic placeholder image

Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Optimization and Effect of Substituents on the Transformation of 3-(Substituted acetoxy)azetidin-2-ones to Chiral 3-Hydroxyazetidin-2-ones, Molecular Docking and Enantiomeric Excess Determination

Author(s): Aman Bhalla*, Garima Modi, Pankaj Kumar, Jaswinder Kaur, Shiwani Berry, Shamsher S. Bari and Bimal K. Banik

Volume 21, Issue 6, 2024

Published on: 19 January, 2024

Page: [520 - 529] Pages: 10

DOI: 10.2174/0115701786273862231116105938

Price: $65

Abstract

The enantioselective synthesis of chiral cis-3-hydroxyazetidin-2-ones mediated by Porcine Pancreatic Lipase (PPL) via hydrolysis of cis-3-(chloro acetoxy) azetidin-2-ones in the presence of a phosphate buffer (0.1M, pH = 7.2) in acetonitrile at a temperature range of 25-35 °C was optimized. Under the optimized reaction conditions, the influence of various electron withdrawing/donating/neutral groups on ester functionality of cis-3-(substituted acetoxy)azetidin-2- ones towards hydrolysis was extensively studied, and the bromoacetoxy, propanyloxy, and formyloxy groups provided moderate to good yields of 90%, 91%, and 81%, respectively. Moreover, the chiral cis-3-hydroxyazetidin-2-ones underwent acetylation, and their enantiomeric excess was assessed using the 1H NMR technique, employing chiral shift reagents. To gain insights into the active sites of the biocatalyst, molecular docking studies of compounds 5(a-i) with pancreatic lipase (PDB ID: 1LBS) were carried out. Additionally, the proposed interaction of substituents with the biocatalyst established the absolute stereochemistry of the target chiral cis-3-hydroxyazetidin-2-ones using Seebach's model in comparison to Jone's models.

« Previous Next »
Graphical Abstract

[1]
a) Manhas, M.S.; Van der Veen, J.M.; Wagle, D.R.; Hegde, V.R.; Bari, S.S.; Kosarych, Z.; Gosh, M.; Krishnan, L. Indian J. Chem., 1986, 25B, 1095-1104.;
b) Wasserman, H.H.; Pearce, B.C. Tetrahedron Lett., 1985, 26(18), 2237-2240.
[http://dx.doi.org/10.1016/S0040-4039(00)98971-8]
[2]
Banik, B.K.; Manhas, M.S.; Bose, A.K. J. Org. Chem., 1993, 58(2), 307-309.
[http://dx.doi.org/10.1021/jo00054a007]
[3]
Sinden, S.L.; Durbin, R.D. Nature, 1968, 219(5152), 379-380.
[http://dx.doi.org/10.1038/219379a0] [PMID: 5662152]
[4]
Imada, A.; Kitano, K.; Kintaka, K.; Muroi, M.; Asai, M. Nature, 1981, 289(5798), 590-591.
[http://dx.doi.org/10.1038/289590a0] [PMID: 7007891]
[5]
a) Stewart, W.W. Nature, 1971, 229(5281), 174-178.
[http://dx.doi.org/10.1038/229174a0] [PMID: 4923261];
b) Dolle, R.E.; Hughes, M.J.; Li, C.S.; Kruse, L.I. J. Chem. Soc. Chem. Commun., 1989, (19), 1448-1449.
[http://dx.doi.org/10.1039/c39890001448];
c) Greenlee, W.J.; Springer, J.P.; Patchett, A.A. J. Med. Chem., 1989, 32(1), 165-170.
[http://dx.doi.org/10.1021/jm00121a030] [PMID: 2562853];
d) Baldwin, J.E.; Otsuka, M.; Wallace, P.M. Tetrahedron, 1986, 42(12), 3097-3110.
[http://dx.doi.org/10.1016/S0040-4020(01)87377-4]
[6]
a) Ojima, I.; Habus, I.; Zhao, M.; Georg, G.I.; Jayasinghe, L.R. J. Org. Chem., 1991, 56(5), 1681-1683.
[http://dx.doi.org/10.1021/jo00005a003];
b) Georg, G.I.; Harriman, G.C.B.; Hepperle, M.; Clowers, J.S.; Vander Velde, D.G.; Himes, R.H. J. Org. Chem., 1996, 61(8), 2664-2676.
[http://dx.doi.org/10.1021/jo951961c] [PMID: 11667096]
[7]
Chincholkar, P.M.; Kale, A.S.; Gumaste, V.K.; Deshmukh, A.R.A.S. Tetrahedron, 2009, 65(12), 2605-2609.
[http://dx.doi.org/10.1016/j.tet.2008.11.042]
[8]
Mishra, R.K.; Coates, C.M.; Revell, K.D.; Turos, E. Org. Lett., 2007, 9(4), 575-578.
[http://dx.doi.org/10.1021/ol062752p] [PMID: 17286366]
[9]
Palomo, C.; Cossío, F.P.; Ontoria, J.M.; Odriozola, J.M. Tetrahedron Lett., 1991, 32(26), 3105-3108.
[http://dx.doi.org/10.1016/0040-4039(91)80701-7]
[10]
a) Ojima, I.; Habus, I.; Zhao, M.; Zucco, M.; Park, Y.H.; Sun, C.M.; Brigaud, T. Tetrahedron, 1992, 48(34), 6985-7012.
[http://dx.doi.org/10.1016/S0040-4020(01)91210-4];
b) Georg, G.I.; Cheruvallath, Z.S.; Harriman, G.C.B.; Hepperle, M.; Park, H. Bioorg. Med. Chem. Lett., 1993, 3(11), 2467-2470.
[http://dx.doi.org/10.1016/S0960-894X(01)80979-3];
c) Ojima, I.; Kuduk, S.D.; Slater, J.C.; Gimi, R.H.; Sun, C.M. Tetrahedron, 1996, 52(1), 209-224.
[http://dx.doi.org/10.1016/0040-4020(95)00865-6]
[11]
a) Shinkre, B.A.; Puranik, V.G.; Bhawal, B.M.; Deshmukh, A.R.A.S. Tetrahedron Asymmetry, 2003, 14(4), 453-459.
[http://dx.doi.org/10.1016/S0957-4166(03)00039-9];
b) Mollet, K.; Goossens, H.; Piens, N.; Catak, S.; Waroquier, M.; Törnroos, K.W.; Van Speybroeck, V.; D’hooghe, M.; De Kimpe, N. Chemistry, 2013, 19(10), 3383-3396.
[http://dx.doi.org/10.1002/chem.201203314] [PMID: 23348746];
c) Srirajan, V.; Deshmukh, A.R.A.S.; Bhawal, B.M. Tetrahedron, 1996, 52(15), 5585-5590.
[http://dx.doi.org/10.1016/0040-4020(96)00200-1];
d) Palomo, C.; Aizpurua, J.M.; Ganboa, I.; Maneiro, E.; Odriozola, B. J. Chem. Soc. Chem. Commun., 1994, (12), 1505-1507.
[http://dx.doi.org/10.1039/C39940001505]
[12]
a) Barbaro, G.; Battaglia, A.; Guerrini, A.; Bertucci, C. J. Org. Chem., 1999, 64(13), 4643-4651.
[http://dx.doi.org/10.1021/jo9822481] [PMID: 11674534];
b) Barbaro, G.; Battaglia, A.; Guerrini, A.; Bertucci, C. Tetrahedron Asymmetry, 1997, 8(15), 2527-2531.
[http://dx.doi.org/10.1016/S0957-4166(97)00303-0];
c) Guerrini, A.; Varchi, G.; Samorì, C.; Daniele, R.; Arturo, B. Tetrahedron Lett., 2007, 48(29), 5081-5085.
[http://dx.doi.org/10.1016/j.tetlet.2007.05.087];
d) Battaglia, A.; Barbaro, G.; Giorgianni, P.; Guerrini, A.; Pepe, A. Tetrahedron Asymmetry, 2001, 12, 1015-1023.
[http://dx.doi.org/10.1016/S0957-4166(01)00173-2];
e) Cossío, F.P.; Palomo, C. Tetrahedron Lett., 1985, 26(35), 4239-4242.
[http://dx.doi.org/10.1016/S0040-4039(00)99002-6]
[13]
a) Holton, R.A.; Liu, J.H. Bioorg. Med. Chem. Lett., 1993, 3(11), 2475-2478.
[http://dx.doi.org/10.1016/S0960-894X(01)80981-1];
b) Palomo, C.; Aizpurua, J.M.; Lopez, M.C.; Aurrekoetxea, N.; Oiarbide, M. Tetrahedron Lett., 1990, 31, 6425-6428.
[http://dx.doi.org/10.1016/S0040-4039(00)97082-5]
[14]
a) Banik, B.K.; Negi, M.; Manhas, M.S.; Bose, A.K. Mol. Med. Rep., 2010, 3(2), 317-318.
[http://dx.doi.org/10.3892/mmr_000000258] [PMID: 21472240];
b) Bari, S.S.; Madan, S.; Sethi, M.K. Indian J. Chem., 1999, 38B, 10-17.;
c) Yang, Y.; Wang, J.; Kayser, M. Tetrahedron Asymmetry, 2007, 18(17), 2021-2029.
[http://dx.doi.org/10.1016/j.tetasy.2007.08.012]
[15]
a) Vijeata, A.; Chaudhary, G.R.; Bhalla, A.; Chaudhary, S. ACS Appl. Bio Mater., 2023, 6(5), 1849-1862.
[http://dx.doi.org/10.1021/acsabm.3c00064] [PMID: 37076450];
b) Saini, P.; Thakur, S.; Garg, A.; Bari, S.S.; Bhalla, A. J. Sulfur Chem., 2023, 1-16.;
c) Saini, P.; Bari, S.S.; Yadav, P.; Khullar, S.; Mandal, S.K.; Bhalla, A. ChemistrySelect, 2022, 7(37), e202202172.
[http://dx.doi.org/10.1002/slct.202202172];
d) Saini, P.; Bari, S.S.; Thakur, S.; Garg, A.; Kumar, S.; Mandal, S.K.; Bhalla, A. Synth. Commun., 2022, 52(17), 1742-1755.
[http://dx.doi.org/10.1080/00397911.2022.2112606];
e) Narula, D.; Bari, S.S.; Yadav, P.; Khullar, S.; Mandal, S.K.; Kaur, G.; Chaudhary, G.R.; Bhalla, A. ChemistrySelect, 2021, 6(16), 3932-3940.
[http://dx.doi.org/10.1002/slct.202101104];
f) Bhalla, J.; Bari, S.S.; Chaudhary, G.R.; Kumar, A.; Rathee, A.; Sharma, R.; Bhalla, A. Synth. Commun., 2021, 51, 3758-3767.
[http://dx.doi.org/10.1080/00397911.2021.1992441]
[16]
Bhalla, A.; Modi, G.; Kaur, J.; Kumar, P.; Bari, S.S. Lett. Org. Chem., 2023, 20(9), 883-891.
[http://dx.doi.org/10.2174/1570178620666230417084129]
[17]
a) Barbosa, M.S.; Freire, C.C.C.; Almeida, L.C.; Freitas, L.S.; Souza, R.L.; Pereira, E.B.; Mendes, A.A.; Pereira, M.M.; Lima, Á.S.; Soares, C.M.F. Biotechnol. Appl. Biochem., 2019, 66(5), 823-832.
[http://dx.doi.org/10.1002/bab.1793] [PMID: 31206795];
b) Casajus, H.; Dubreucq, E.; Tranchimand, S.; Perrier, V.; Nugier-Chauvin, C.; Cammas-Marion, S. Biomacromolecules, 2020, 21(7), 2874-2883.
[http://dx.doi.org/10.1021/acs.biomac.0c00593] [PMID: 32551525]
[18]
Kalaritis, P.; Regenye, R.W.; Partridge, J.J.; Coffen, D.L. J. Org. Chem., 1990, 55(3), 812-815.
[http://dx.doi.org/10.1021/jo00290a007]
[19]
a) Basak, A.; Mahato, T.; Bhattacharya, G.; Mukherjee, B. Tetrahedron Lett., 1997, 38(4), 643-646.
[http://dx.doi.org/10.1016/S0040-4039(96)02381-7];
b) Basak, A.; Bhattacharya, G.; Bdour, H.M.M. Tetrahedron, 1998, 54(23), 6529-6538.
[http://dx.doi.org/10.1016/S0040-4020(98)00313-5]
[20]
Moyna, G.; Williams, H.J.; Scott, A.I. Synth. Commun., 1997, 27(9), 1561-1567.
[http://dx.doi.org/10.1080/00397919708006094]
[21]
Ehrler, J.; Seebach, D. Liebigs Ann. Chem., 1990, 1990(4), 379-388.
[http://dx.doi.org/10.1002/jlac.199019900172]
[22]
a) Hultin, P.G.; Jones, J.B. Tetrahedron Lett., 1992, 33(11), 1399-1402.
[http://dx.doi.org/10.1016/S0040-4039(00)91631-9];
b) Hultin, P.G. Ph. D. Thesis, University of Toronto 1988.
[23]
Choudhary, M.I.; Shaikh, M. PLoS One, 2020, 15, 0235030.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy