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498 Chapter 26 AMINO ACIDS, PEPTIDES, PROTEINS, AND NUCLEIC ACIDS: NITROGEN-CONTAINING POLYMERS IN NATURE DCC Dil. 3. Boc-Phe Leu-OCH₃ Boc-Phe-Leu-OCH₃ Phe-Leu-OCH₃ 00 4. Gly + Boc-Gly (N-protected Gly) DCC Dil. 5. Boc-Gly + Phe-Leu-OCH₃ Boc-Gly-Phe-Leu-OCH₃ Gly-Phe-Leu-OCH₃ DCC 6. Boc-Gly again + Gly-Phe-Leu-OCH₃ Dil. Gly-Gly-Phe-Leu-OCH₃ 00 7. Tyr + excess Boc-Tyr (N- and phenolic O-protected Tyr) DCC 8. Boc-Tyr + Gly-Gly-Phe-Leu-OCH₃ 1. H⁺, H₂O 2. H₂O Boc-Tyr-Gly-Gly-Phe-Leu-OCH₃ Tyr-Gly-Gly-Phe-Leu Leu-enkephalin 00 Cbz-Cl 56. 1. His ring N-protected (Cbz) His amine N-protected Boc-(Cbz)His The purpose here is to block both reactive nitrogens of His differently. The Boc group will be later removed by acid to allow a peptide bond to be formed, while the ring N remains Cbz protected. CH₃OH, 2. Pro Pro-OCH₃ (C-protected Pro) DCC 3. Boc-(Cbz)His + Pro-OCH₃ Dil. Boc-(Cbz)His-Pro-OCH₃ (Cbz)His-Pro-OCH₃ 135-140°C 4. Glu pyroglutamic acid Amine group is now an amide, so no further protection is necessary. DCC 5. Pyroglutamic acid + (Cbz)His-Pro-OCH₃ 1. 2. DCC 3. Pd pyroglutamoyl-(Cbz)His-Pro-NH₂ TRH