1559r.ah26.454-46910/20/0515:39Page464 464.chapter 26 AMINO ACIDS,PEPTIDES,PROTEINS,AND NUCLEI ACIDS:NITROGEN-CONTAINING POLYMERS IN NATURE arboxy-proLeu 3.,C Boc-Phe-Leu-OCH,Phe-Lew-OCH 00 4.Gly +(CHs)scocoCOC(CH3)-Boc-Gly 5.Boc-Gly+Phe-Lew-CHc Boc-Gly-Phe-Le-CH,Gly-Phe-Leu-OCH Boc-Gly again+Gly-Phe-Leu-OCH DCC Bo-Gly-Gye-LeCHGly-ly--Le-CH 00 7.Tyr excess (CHs)sCOCOCOC(CH3)3-Boc-Tyr 8.Bo-Tyr+Gly-Gly-Phe-Leu-OCH Dcc Boc-Ty-p的-O-Phe-e-CH品 Tyr-Gly-Gly-Phe-Leu Leu-enkephalin 00 9.1.Hisring N-protected (Ch)Hisamine N-protected Boc-(Cbis 2.Pro CH:OH.H 3.Bo-ChsPro-CHBoc-(Ch)-CH,(CCH Progumoy-Ch2)Hi-o-NHTRH2. 3. 4. 5. 6. 7. 8. 49. 1. 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. 2. 3. 4. 5. pyroglutamoyl-(Cbz)His-Pro-NH2 H2, Pd TRH pyroglutamoyl-(Cbz)His-Pro-OCH3 1. HO, H2O 2. DCC 3. NH3 (Cbz)His-Pro-OCH3 DCC Pyroglutamic acid Glu pyroglutamic acid 135–140C Amine group is now an amide, so no further protection is necessary. Pro-OCH3 Boc-(Cbz)His-Pro-OCH3 DCC Dil. H Boc-(Cbz)His (Cbz)His-Pro-OCH 3 Pro Pro-OCH3 CH3OH, H (C-protected Pro) (CH3)3COCOCOC(CH3)3 O O ring N-protected (Cbz) His amine N-protected Boc-(Cbz)His Cbz-Cl His Boc-Tyr-Gly-Gly-Phe-Leu-OCH3 Tyr-Gly-Gly-Phe-Leu 1. H, H2O 2. HO, H2O Leu-enkephalin Gly-Gly-Phe-Leu-OCH3 DCC Boc-Tyr Tyr excess (CH3)3COCOCOC(CH3)3 O O Boc-Tyr (N- and phenolic O-protected Tyr) Boc-Gly-Gly-Phe-Leu-OCH3 Dil. H Gly-Gly-Phe-Leu-OCH3 Gly-Phe-Leu-OCH3 DCC Boc-Gly again Phe-Leu-OCH3 Boc-Gly-Phe-Leu-OCH3 DCC Dil. H Boc-Gly Gly-Phe-Leu-OCH 3 Gly (CH3)3COCOCOC(CH3)3 O O Boc-Gly (N-protected Gly) Leu-OCH3 Boc-Phe-Leu-OCH3 DCC Dil. H Boc-Phe Phe-Leu-OCH 3 Leu Leu-OCH3 CH3OH, H (Methyl ester: carboxy-protected Leu) 464 • Chapter 26 AMINO ACIDS, PEPTIDES, PROTEINS, AND NUCLEIC ACIDS: NITROGEN-CONTAINING POLYMERS IN NATURE 1559T_ch26_454-468 10/20/05 15:39 Page 464