Synlett 2006(9): 1311-1314  
DOI: 10.1055/s-2006-939717
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Cyclization of Peptides on SynPhaseTM Lanterns

Sylvie Monroc, Lidia Feliu, Marta Planas, Eduard Bardají*
Laboratori d’Innovació en Processos i Productes de Síntesi Orgànica, Departament de Química, Universitat de Girona, Campus de Montilivi, 17071 Girona, Spain
Fax: +34(972)418150; e-Mail: eduard.bardaji@udg.es;
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Publikationsverlauf

Received 1 February 2006
Publikationsdatum:
22. Mai 2006 (online)

Abstract

SynPhase lanterns and microwave irradiation have been combined to set up an efficient and rapid cyclization strategy of short peptides.

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SynPhaseTM lanterns were purchased from Mimotopes, Pty Ltd, Clayton, Australia.

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After allyl removal, lanterns were washed with CHCl3-AcOH-NMM (37:2:1, 3 × 2 min), DIPEA-CH2Cl2 (1:19, 3 × 5 min), sodium N,N-diethyldithiocarbamate (0.03 M in NMP, 3 × 15 min), NMP (5 × 5 min) and CH2Cl2 (5 × 5 min).

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All microwave experiments were performed using the microwave Ethos SEL labstation from Milestone equipped with a dual magnetron system (1600 W). The experiment time, temperature and power were controlled with the EasyControl software package. The temperature was monitored through the ATC-400FO Automatic Fiber Optic Temperature Control System immersed into a standard Milestone reference vessel. This equipment regulates the power to achieve and maintain the selected temperature. Firstly, a microwave ramp (500 W max.) was applied for
5 min to reach a 50 °C temperature. Each linear peptide anchored to the SynPhase lantern (five stacked disks), immersed into a solution of PyBOP (16 equiv), HOBt
(16 equiv), and DIPEA (32 equiv) in 1 mL of NMP, was irradiated at this temperature for periods of 15 min (2 ×
15 min or 4 × 15 min). After the total reaction time, upon cooling, the solvent was removed and the lantern was washed in NMP (3 × 5 min) and CH2Cl2 (3 × 5 min). The compound was cleaved from the lantern using a solution of TFA-H2O-TIS (95:2.5:2.5). After 1 h at r.t., the lantern was removed, the solution was concentrated under a stream of N2 and the compound was precipitated with dry Et2O, centri-fuged and decanted. The final cyclopeptide was analyzed by HPLC and characterized by FAB-MS or ESI-MS.