Exploring a Sulfone Linker Utilizing Trimethyl Aluminum As a Cleavage Reagent: Solid-phase Synthesis of Sulfonamides and Ureas

Overview

Journal Mol Divers

Date 2012 Jul 4

PMID 22752658

Authors

Tsai-Wen Chung

Chih-Hau Chen

Chu-Chung Lin

Hsien-Jen Wu

Chung-Ming Sun

Wen-Sheng Chung

Affiliations

Soon will be listed here.

Abstract

A novel and efficient cleavage reagent, trimethyl aluminum, for traceless sulfinate-functionalized resin has been developed. The synthesis of sulfonamide and urea derivatives via a traceless solid-phase sulfone linker strategy through six synthetic steps comprising utilization of trimethyl aluminum as a novel cleavage reagent was also established. An insight of the plausible mechanism of the cleavage reaction was discussed.

References

Ni B, Zhang Q, Dhungana K, Headley A . Ionic liquid-supported (ILS) (S)-pyrrolidine sulfonamide, a recyclable organocatalyst for the highly enantioselective Michael addition to nitroolefins. Org Lett. 2009; 11(4):1037-40. DOI: 10.1021/ol900003e. View

Padwa A, Nara S, Wang Q . Dichloroketene-induced cyclizations of vinyl sulfilimines: application of the method in the synthesis of (+/-)-desoxyeseroline. J Org Chem. 2005; 70(21):8538-49. DOI: 10.1021/jo051550o. View

Pacchiano F, Carta F, McDonald P, Lou Y, Vullo D, Scozzafava A . Ureido-substituted benzenesulfonamides potently inhibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis. J Med Chem. 2011; 54(6):1896-902. DOI: 10.1021/jm101541x. View

Hacker H, Leyers S, Wiendlocha J, Gutschow M, Wiese M . Aromatic 2-(thio)ureidocarboxylic acids as a new family of modulators of multidrug resistance-associated protein 1: synthesis, biological evaluation, and structure-activity relationships. J Med Chem. 2009; 52(15):4586-95. DOI: 10.1021/jm900688v. View

Hisamatsu Y, Shirai N, Ikeda S, Odashima K . A new quadruple hydrogen-bonding module based on five-membered heterocyclic urea structure. Org Lett. 2010; 12(8):1776-9. DOI: 10.1021/ol100385b. View

Sun D, Lee R . Solid-phase synthesis of a thymidinyl dipeptide urea library. J Comb Chem. 2007; 9(3):370-85. PMC: 2532789. DOI: 10.1021/cc060154w. View

Huang S, Li H, Liu J, Morisseau C, Hammock B, Long Y . Incorporation of piperazino functionality into 1,3-disubstituted urea as the tertiary pharmacophore affording potent inhibitors of soluble epoxide hydrolase with improved pharmacokinetic properties. J Med Chem. 2010; 53(23):8376-86. PMC: 3070159. DOI: 10.1021/jm101087u. View

Gutierrez C, Bavetsias V, McDonald E . ClTi(OiPr)3-promoted reductive amination on the solid phase: combinatorial synthesis of a biaryl-based sulfonamide library. J Comb Chem. 2008; 10(2):280-4. DOI: 10.1021/cc700132f. View

Gao Y, Lam Y . [3+2] cycloaddition reactions in the solid-phase synthesis of 1,2,3-triazoles. Org Lett. 2006; 8(15):3283-5. DOI: 10.1021/ol0611494. View

10.

Chu W, Rothfuss J, Chu Y, Zhou D, Mach R . Synthesis and in vitro evaluation of sulfonamide isatin Michael acceptors as small molecule inhibitors of caspase-6. J Med Chem. 2009; 52(8):2188-91. DOI: 10.1021/jm900135r. View

11.

Kurosu M, Biswas K, Crick D . Polymer-supported (2,6-dichloro- 4-alkoxyphenyl)(2,4-dichlorophenyl)methanol: a new linker for solid-phase organic synthesis. Org Lett. 2007; 9(6):1141-4. PMC: 2577291. DOI: 10.1021/ol070150f. View

12.

Rainier J, Cox J . Aluminum- and boron-mediated c-glycoside synthesis from 1,2-anhydroglycosides. Org Lett. 2000; 2(17):2707-9. DOI: 10.1021/ol006286u. View

13.

Wills A, Balasubramanian S . Recent developments in linker design and application. Curr Opin Chem Biol. 2003; 7(3):346-52. DOI: 10.1016/s1367-5931(03)00035-8. View

14.

Gil C, Brase S . Traceless and multifunctional linkers for the generation of small molecules on solid supports. Curr Opin Chem Biol. 2004; 8(3):230-7. DOI: 10.1016/j.cbpa.2004.04.004. View

15.

Cheng W, Wong M, Olmstead M, Kurth M . Solid-phase synthesis of novel isoxazolocyclobutanones and isoxazolinocyclobutenones. Org Lett. 2002; 4(5):741-4. DOI: 10.1021/ol017194n. View

16.

Sasaki M, Tanino K, Miyashita M . Stereospecific alkyl and alkynyl substitution reactions of epoxy sulfides with organoaluminums with double inversion of the configuration. J Org Chem. 2001; 66(16):5388-94. DOI: 10.1021/jo010240c. View

17.

Chen Y, Lam Y, Lai Y . Solid-phase synthesis of pyrazolines and isoxazolines with sodium benzenesulfinate as a traceless linker. Org Lett. 2003; 5(7):1067-9. DOI: 10.1021/ol0340888. View

18.

Tsvelikhovsky D, Gelman D, Molander G, Blum J . Lanthanide-promoted ethylation of Schiff bases by triethylaluminum. Org Lett. 2004; 6(12):1995-7. DOI: 10.1021/ol049420+. View

19.

Chen Y, Lam Y, Lai Y . Solid-phase synthesis of imidazo[1,2-a]pyridine using sodium benzenesulfinate as a traceless linker. Org Lett. 2003; 4(22):3935-7. DOI: 10.1021/ol026797b. View

20.

MERRIFIELD R . Automated synthesis of peptides. Science. 1965; 150(3693):178-85. DOI: 10.1126/science.150.3693.178. View