Forging Structural Complexity: Diastereoselective Synthesis of Densely Substituted β-lactams with Dual Functional Handles for Enhanced Core Modifications

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Aug 22

PMID 39170719

Authors

Agustin M Rodriguez Trevino

Pierre Loch-Temzelides

Sanjay Pandiri

Justin K Kirkland

Michael T Davenport

Ulises Aguinaga

Muhammed Yousufuddin

Daniel H Ess

Laszlo Kurti

Affiliations

Soon will be listed here.

Abstract

The preparation of the β-lactam motif containing both C-Br and N-O bonds as functional handles remains an unmet synthetic challenge. Described herein is a novel and highly diastereoselective NBS-mediated cyclization of alkoxy α,β-unsaturated silyl imino ethers to furnish nearly three dozen α-bromo -alkoxy β-lactams. The reaction gives rapid and convenient access to structurally diverse monocyclic, spirocyclic and fused β-lactams in moderate to good yields. The two functional handles were shown to be useful for the further elaboration of the β-lactam core.

References

Yang W, Ling B, Hu B, Yin H, Mao J, Walsh P . Synergistic N-Heterocyclic Carbene/Palladium-Catalyzed Umpolung 1,4-Addition of Aryl Iodides to Enals. Angew Chem Int Ed Engl. 2019; 59(1):161-166. DOI: 10.1002/anie.201912584. View

Zhang N, Yang R, Zhang-Negrerie D, Du Y, Zhao K . Direct conversion of N-alkoxyamides to carboxylic esters through tandem NBS-mediated oxidative homocoupling and thermal denitrogenation. J Org Chem. 2013; 78(17):8705-11. DOI: 10.1021/jo401435v. View

Alcaide B, Almendros P, Cabrero G, Ruiz M . Stereocontrolled access to orthogonally protected anti,anti-4-aminopiperidine-3,5-diols through chemoselective reduction of enantiopure beta-lactam cyanohydrins. J Org Chem. 2007; 72(21):7980-91. DOI: 10.1021/jo701452a. View

Decamps S, Sevaille L, Ongeri S, Crousse B . Access to novel functionalized trifluoromethyl β-lactams by ring expansion of aziridines. Org Biomol Chem. 2014; 12(33):6345-8. DOI: 10.1039/c4ob01262c. View

Benfatti F, Cardillo G, Gentilucci L, Perciaccante R, Tolomelli A, Catapano A . Synthesis and biological evaluation of azido- and aziridino-hydroxyl-beta-lactams through stereo- and regioselective epoxide ring opening. J Org Chem. 2006; 71(24):9229-32. DOI: 10.1021/jo0615652. View

Durham T, Miller M . Enantioselective synthesis of alpha-amino acids from N-tosyloxy beta-lactams derived from beta-keto esters. J Org Chem. 2003; 68(1):27-34. DOI: 10.1021/jo0162437. View

Hosseyni S, Jarrahpour A . Recent advances in β-lactam synthesis. Org Biomol Chem. 2018; 16(38):6840-6852. DOI: 10.1039/c8ob01833b. View

Bellettini J, Miller M . Intermolecular Addition of Amines to an N-Tosyloxy beta-Lactam(1). J Org Chem. 1996; 61(22):7959-7962. DOI: 10.1021/jo961184w. View

Joyeau R, Molines H, Labia R, Wakselman M . N-aryl 3-halogenated azetidin-2-ones and benzocarbacephems, inhibitors of beta-lactamases. J Med Chem. 1988; 31(2):370-4. DOI: 10.1021/jm00397a018. View

10.

Bandini , Favi , MARTELLI , Panunzio , Piersanti . A trans-stereoselective synthesis of 3-Halo-4-alkyl(aryl)-NH-azetidin-2-ones. Org Lett. 2000; 2(8):1077-9. DOI: 10.1021/ol005633x. View

11.

Wang F, Liu L, Yang C, Luan C, Yang J, Chen J . Synthesis of α-Quaternary β-Lactams via Copper-Catalyzed Enantioconvergent Radical C(sp )-C(sp ) Cross-Coupling with Organoboronate Esters. Angew Chem Int Ed Engl. 2022; 62(2):e202214709. DOI: 10.1002/anie.202214709. View

12.

Lima L, da Silva B, Barbosa G, Barreiro E . β-lactam antibiotics: An overview from a medicinal chemistry perspective. Eur J Med Chem. 2020; 208:112829. DOI: 10.1016/j.ejmech.2020.112829. View

13.

Deketelaere S, Van Nguyen T, Stevens C, Dhooghe M . Synthetic Approaches toward Monocyclic 3-Amino-β-lactams. ChemistryOpen. 2017; 6(3):301-319. PMC: 5474669. DOI: 10.1002/open.201700051. View

14.

DEMAIN A, Elander R . The beta-lactam antibiotics: past, present, and future. Antonie Van Leeuwenhoek. 1999; 75(1-2):5-19. DOI: 10.1023/a:1001738823146. View

15.

Bush K, Bradford P . Interplay between β-lactamases and new β-lactamase inhibitors. Nat Rev Microbiol. 2019; 17(5):295-306. DOI: 10.1038/s41579-019-0159-8. View

16.

Homsi F, Rousseau G . 4-Endo-Trig Cyclization Processes Using Bis(collidine)bromine(I) Hexafluorophosphate as Reagent: Preparation of 2-Oxetanones, 2-Azetidinones, and Oxetanes. J Org Chem. 2001; 64(1):81-85. DOI: 10.1021/jo9810361. View

17.

Saura-Sanmartin A, Andreu-Ardil L . Stereoselective synthesis of β-lactams: recent examples. Org Biomol Chem. 2023; 21(16):3296-3306. DOI: 10.1039/d3ob00309d. View

18.

Koch V, Lorion M, Barde E, Brase S, Cossy J . Cobalt-Catalyzed α-Arylation of Substituted α-Halogeno β-Lactams. Org Lett. 2019; 21(16):6241-6244. DOI: 10.1021/acs.orglett.9b02122. View

19.

Thakuria B, Lahon K . The Beta Lactam Antibiotics as an Empirical Therapy in a Developing Country: An Update on Their Current Status and Recommendations to Counter the Resistance against Them. J Clin Diagn Res. 2013; 7(6):1207-14. PMC: 3708238. DOI: 10.7860/JCDR/2013/5239.3052. View

20.

Georgopapadakou N, Smith S, Sykes R . Mode of action of azthreonam. Antimicrob Agents Chemother. 1982; 21(6):950-6. PMC: 182051. DOI: 10.1128/AAC.21.6.950. View