Submit Manuscript  

Article Details


Biocatalytic Production of Chiral Benzotriazoles Employing Conventional Heating and Microwave Radiation

[ Vol. 4 , Issue. 3 ]

Author(s):

Matheus A. Meirelles, Alex H. Jeller, Irlon M. Ferreira, Cristiano Raminelli, Raquel S. Faria, Elisângela de Paula Silveira-Lacerda and André L. M. Porto   Pages 191 - 198 ( 8 )

Abstract:


Background: This paper describes the synthesis of chiral 1,2,3-benzotriazoles by the enzymatic kinetic resolution of β-azidoalcohols using lipase from Candida antarctica B followed by a [3+2] cycloaddition reaction involving benzyne formation from 2-(trimethylsilyl)phenyl triflate and CsF under conventional heating and microwave radiation. (±)-1,2,3-Benzotriazoles were tested in vitro to evaluate their cytotoxic effects on S180 tumor cells using the colorimetric MTT assay. They showed IC50 values comparable to the IC50 value of cisplatin.

Methods: Synthesis of azidoalcohols and 1,2,3-benzotriazoles were carried out under microwave radiation and conventional heating. Enzymatic kinetic resolution of (±)-azidoalcohols were obtained by Candida antarctica B in orbital shaker. Enzymatic reactions were analyzed using Shimadzu LC-10AD HPLC equipment with UV detector (190-254 nm) and Chiralcel OD-H chiral column (0.46 cm × 25 cm; 5 µm).

Results: Preparation of (±)-azidoalcohols was used the corresponding epoxides and NaN3 in water at 90°C. When the reactions were performed under microwave heating, the compounds were obtained in higher yields (80 and 85%, respectively) and shorter reaction times (10 and 90 min, respectively) versus conventional heating. The (±)-1,2,3-benzotriazoles were produced by the [3+2] cycloaddition reaction between (±)-azidoalcohols and 2-(trimethylsilyl)phenyl triflate in the presence of CsF using acetonitrile as solvent at 70°C under conventional heating or microwave radiation. CAL-B was employed in kinetic resolution of (±)-azidoalcohols yielding enantioenriched products. cytotoxic effects on S180 tumor cells using the colorimetric MTT assay.

Conclusion: Chiral 1,2,3-benzotriazoles were synthesized from enzymatic kinetic resolution of (±)- azidoalcohols using Candida antarctica B followed by a [3+2] cycloaddition reaction involving the benzyne formation from 2-(trimethylsilyl)phenyl triflate and CsF under conventional heating and microwave radiation. The chiral 1,2,3-benzotriazoles were obtained after 15 min under microwave radiation with 55-56% yields. The (±)-1,2,3-benzotriazoles were tested in vitro to evaluate their cytotoxic effects on S180 tumor cell line using the colorimetric MTT assay and showed IC50 values comparable to the IC50 value of cisplatin.

Keywords:

1, 2, 3-benzotriazoles, biocatalysis, CAL-B, microwave radiation, β-azidoalcohols.

Affiliation:

Laboratório de Química Orgânica e Biocatálise, Instituto de Química de São Carlos, Universidade de São Paulo, Av. João Dagnone, Ed. Química Ambiental, J. Santa Angelina, 1100, 13563-120 São Carlos, São Paulo, Laboratório de Química Orgânica e Biocatálise, Instituto de Química de São Carlos, Universidade de São Paulo, Av. João Dagnone, Ed. Química Ambiental, J. Santa Angelina, 1100, 13563-120 São Carlos, São Paulo, Laboratório de Química Orgânica e Biocatálise, Instituto de Química de São Carlos, Universidade de São Paulo, Av. João Dagnone, Ed. Química Ambiental, J. Santa Angelina, 1100, 13563-120 São Carlos, São Paulo, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Rua Prof. Artur Riedel, 275, 09972-270, Diadema, SP, Laboratório de Genética Molecular e Citogenética, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Rua R-2a, Campus Samambaia, 74690-900, Goiânia, Goiás, Laboratório de Genética Molecular e Citogenética, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Rua R-2a, Campus Samambaia, 74690-900, Goiânia, Goiás, Laboratório de Química Orgânica e Biocatálise, Instituto de Química de São Carlos, Universidade de São Paulo, Av. João Dagnone, Ed. Química Ambiental, J. Santa Angelina, 1100, 13563-120 São Carlos, São Paulo

Graphical Abstract:



Read Full-Text article