Diisopropylethylamine → (S)-2-amino-N-((S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)propanamide

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Reaction Conditions

Reaction Steps

The H-Ala-Tyr-NH2 and H-Ala-Ala-Tyr-NH2 peptides were prepared by solid phase synthesis using a Liberty microwave peptide synthesizer (CEM Corp., Matthews, N.C.). The Fmoc deprotection and the coupling steps were performed at 75° C. using microwave heating provided by power pulsing sequences of 20 W. The reaction temperatures were monitored with a fiberoptic probe inserted into the reaction vessel. The synthesis was started from 1.0 mmol of Fmoc-protected Sieber amide resin (0.72 mmol/g) placed into a 50 mL polypropylene vessel. The amino acids were coupled using the 1.0 mmol scale method provided by the manufacturer. At the beginning of each coupling step, the Fmoc group was removed by two 5 minute treatment with 5% piperazine in DMF containing 0.1 M HOBt. After 5 20 mL DMF washes, Fmoc-Ala-OH and Fmoc-Tyr(tBu)-OH were successively coupled by activation with 0.5 M HCTU (4 eq.) in DMF and 2 M DIEA (8 eq.) in NMP for 5 minutes. At the end of each coupling, the resin was washed with 5 20 mL DMF washes. Upon completion of the sequence assembly, the resin was washed with DCM and dried in vacuo. The peptides were then released from their respective resins by treatment with (95:5) TFA/water (10 mL) for 90 minutes at room temperature. The spent resin was filtered off and rinsed with additional cleavage solution (2×3 mL). The combined filtrates were evaporated to −4 mL and the product was precipitated by addition of ether (45 mL). The precipitated product was cooled to 0° C. for 30 minutes, collected by centrifugation, washed with additional ether and dried to yield an off-white solid in 85-90% yield.

Provenance & Evidence