Microwave-Assisted Cyclization of Peptides on SynPhase^TM Lanterns

Abstract

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

Key words

SynPhase lanterns - microwave - cyclization - cyclic peptides

References and Notes

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9

SynPhase^TM lanterns were purchased from Mimotopes, Pty Ltd, Clayton, Australia.

10

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).

12

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.