BiocatalyticProduction of Chiral Benzotriazoles Employing Conventional Heating and Microwave Radiation

• Published in: Current Microwave Chemistry
• Main Authors: Meirelles, Matheus A., Jeller, Alex H., Ferreira, Irlon M., Raminelli, Cristiano, Faria, Raquel S., Silveira-Lacerda, Elisangela de Paula, Porto, Andre L. M.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Bentham Science Publ Ltd 2017
• Subjects: 1,2,3-benzotriazoles; biocatalysis; CAL-B; microwave radiation; beta-azidoalcohols; Rua; Antarc*; Antarctica
• Online Access: https://repositorio.unifesp.br/handle/11600/55469; https://doi.org/10.2174/2213335603666161101152243

Background: This paper describes the synthesis of chiral 1,2,3-benzotriazoles by the enzymatic kinetic resolution of beta-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 +/- m). Results: Preparation of (+/-)-azidoalcohols was used the corresponding epoxides and NaN3 in water at 90 degrees 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 degrees 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. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) FAPESP Univ Sao Paulo, Inst Quim Sao Carlos, Lab Quim Organ & Biocatalise, Av Joao Dagnone,Ed Quim Ambiental, BR-13563120 Sao Carlos, SP, Brazil Univ Estadual Mato Grosso do Sul, Coordenacao Quim, Rod Dourados Itahum,Km 12, BR-79804970 Dourados, MS, Brazil Univ Fed Amapa, Colegiado Quim, Grp Biocatalise & Biotransformacao Quim Organ, Rod JK,KM 02, BR-68902280 Macapa, Amapa, Brazil Univ Fed Sao Paulo, Dept Ciencias Exatas & Terra, Rua Prof Artur Riedel 275, BR-09972270 Diadema, SP, Brazil Univ Fed Goias, Inst Ciencias Biol, Lab Genet Mol & Citogenet, Rua R-2a,Campus Samambaia, BR-74690900 Goiania, Go, Brazil Univ Fed Sao Paulo, Dept Ciencias Exatas & Terra, Rua Prof Artur Riedel 275, BR-09972270 Diadema, SP, Brazil FAPESP: 2012/18605-3 FAPESP: 2012/22841-4 Web of Science