2-(Trimethylsilyl)aryl trifluoromethanesulfonates as aryne precursors aiming to the preparation of functionalized (hetero)aromatic compounds and syntheses of bioactive natural products

• Grant number: 20/12530-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2021
• End date: January 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Cristiano Raminelli
• Grantee: Cristiano Raminelli
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Benzyne and its derivatives, called arynes, are highly reactive intermediates, with recognized importance in organic chemistry, successfully employed in syntheses of natural products and preparations of functional materials. In this sense, TMS-aryl trifluoromethanesulfonates have emerged as an important alternative for the formation of benzyne and arynes under mild reaction conditions, enlarging the scope of benzyne chemistry applications in preparative organic chemistry. Within this context, we intend to develop the reaction between TMS-aryl trifluoromethanesulfonates and N-sulfonyl-1,2,3-triazoles in the presence of a source of fluoride ions, using a transition metal as a catalyst, to obtain substituted indole compounds. In parallel, we wish to complete the enantioselective total synthesis of the aporphine alkaloid (S)-nuciferine, employing in the key steps benzyne chemistry and enantioselective hydrogenation. At the same time, we intend to carry out the total synthesis of the ergoline alkaloid (±)-lisergic acid, employing in the key steps Heck reaction and transformation promoted by the formation of aryne. In addition, we wish to perform the semi-syntheses of (-)-cannabidiol and of (+)-cannabidiol investigating mainly the optimization of their corresponding key steps, aiming at pharmacological studies. For the same purpose, we intend to explore the three-component reaction involving TMS-aryl trifluoromethanesulfonates, cyclic allyl acetates, and trifluoromethyl benzoate using a source of fluoride ions, promoting the formation of substituted arylcyclohexene compounds, which comprise the structural core of cannabidiol. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CIPRIANO DA SILVA, TAMIRIS REISSA; OLIVEIRA, RAFAELA BRITO; NICASTRO, ARTHUR LUIZ MIRANDA; URESHINO, RODRIGO PORTES; RAMINELLI, CRISTIANO. Total Synthesis of Aporphine Alkaloids via Benzyne Chemistry: Progress Towards a Late-Stage Enantioselective Hydrogenation and Neuroprotective Activity Evaluations. CHEMISTRYSELECT, v. 8, n. 36, p. 10-pg., 2023-09-26. (20/12530-8, 16/20796-2, 20/04709-8)

TAMIRIS R. C. SILVA; CRISTIANO RAMINELLI. ESTRATÉGIAS PARA A SÍNTESE DO ÁCIDO LISÉRGICO. Química Nova, v. 44, n. 7, p. 852-867, 2021-09-03. (20/12530-8)

RODRIGUES-JUNIOR, DORIVAL MENDES; RAMINELLI, CRISTIANO; HASSANIE, HAIFA; GOULART TROSSINI, GUSTAVO HENRIQUE; PERECIM, GIVAGO PRADO; CAJA, LAIA; MOUSTAKAS, ARISTIDIS; VETTORE, ANDRE LUIZ. Aporphine and isoquinoline derivatives block glioblastoma cell stemness and enhance temozolomide cytotoxicity. SCIENTIFIC REPORTS, v. 12, n. 1, p. 17-pg., 2022-12-07. (20/12530-8, 15/09182-0)

MACHADO, ANDRE CAMPOS; DA SILVA, TAMIRIS REISSA CIPRIANO; RAMINELLI, CRISTIANO; CASELI, LUCIANO. The composition of fusogenic lipid mixtures at the air-water modulates the physicochemical properties changes upon interaction with lysicamine. Biophysical Chemistry, v. 293, p. 8-pg., 2022-12-23. (20/01183-5, 20/12530-8, 18/22214-6, 22/03736-7)

SILVA, TAMIRIS R. C.; RITA, BRUNO H.; RAMINELLI, CRISTIANO. dvances Towards the Synthesis of Aporphine Alkaloids: C-Ring Formation via Approaches Based on One- and Two-Bond Disconnection. CHEMICAL RECORD, v. 22, n. 2, NOV 2021. (20/12530-8)

SILVA, TAMIRIS R. C.; SOUZA, VINICIUS V.; RAMINELLI, CRISTIANO. Synthesis of Isoquinolines via the [4+2] Cycloaddition Reaction of Oxazoles and Arynes. CHEMISTRYSELECT, v. 7, n. 33, p. 4-pg., 2022-09-06. (20/12530-8)

MACHADO, ANDRE CAMPOS; DA SILVA, TAMIRIS REISSA CIPRIANO; RAMINELLI, CRISTIANO; CASELI, LUCIANO. Unsaturation pattern of phosphatidylglycerols modulating the interaction of lysicamine with cells membrane models at the air-water interface. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 222, p. 10-pg., 2023-02-01. (18/22214-6, 19/03239-0, 20/01183-5, 20/12530-8)