KR850002485A - Method for producing novel peptides - Google Patents

Abstract

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Description

Method for producing novel peptides

As this is a public information case, the full text was not included.

Claims (10)

(i) at least one protecting group and general formula (II): X ¹ -R ₁ (X or X ² ) -R ₂ -R ₃ (X ³ ) -Ala-Ile-Phe-Thr (X ⁴ ) -R ₈ (X ⁴ or X ⁵ ) -Ser (X ⁴ ) -R ₁₀ (X ² ) -Arg (X ⁶ ) -R ₁₂ (X ⁶ or X ⁷ ) -R ₁₃ -Leu-R ₁₅ -Gln (X ⁵ ) -R ₁₇ -R ₁₈ (X ² ) -Ala-Arg (X ⁶ ) -Lys (X ⁷ ) -Len-R ₂₃ -R ₂₄ (X or X ⁵ ) -R ₂₅ (X ³ ) -Ile-R ₂₇ -R ₂₈ (X ⁴ or X ⁵ ) -Arg (X ⁶ ) -Gln (X ⁵ ) -Gln (X ₅ ) -Gly-Glu (X ³ ) -R ₃₄ (X ⁴ or X ⁶ ) -Asn ( X ⁵ ) -Gln (X ⁵ ) -Glu (X ³ ) -R ₃₈ (X ⁵ or X ⁶ ) -R ₃₉ (X ⁶ ) -R ₄₀ (X ⁴ )-gives a compound wherein (X ), (X ¹ ), (X ² ), (X ³ ), (X ⁴ ), (X ⁵ ), (X ⁶ ), (X ⁷ ) and (X ⁸ ) are each one of hydrogen or a protecting group And (X ⁹ ) is one of amide or hydroxyl or a protecting group, and (ii) cleaves the protecting group or groups from the compound of formula (II) to form a peptide having formula (I) or a physiologically active segment thereof. And (iii) converting the obtained peptides into non-toxic addition salts as needed. Following order i.e. _{R 1 -R 2 -R 3 -Ala-} Ile-Phe-Thr-R 8 -Ser-R 10 -Arg-R 12 -R 13 -Len-R 15 -Gln-R 17 -R containing ₁₈ -Ala-Arg-Lys-Leu-Leu-R ₂₄ -R ₂₅ -Ile-R ₂₇ -R ₂₈ -Arg-Gln-Gln-Gly-Glu-R ₃₄ -Asn-Gln-Glu-R ₃₈ -R ₃₉ Process for the preparation of novel peptides with -R ₄₀ -Arg-R ₄₂ -R ₄₃ -R ₄₄ . Wherein R ₁ is C ^α Me or N ^α Me substituent or unsubstituted Tyr, D-Tyr, Met, Phe, P-Phe, PCI-Phe, Leu, His is D-His; R ₂ is Ala or D-Ala; R ₃ is Asp or D-Asp; R ₈ is ser, Asn, D-ser or D-Asn; R ₁₀ is Tyr or D-Tyr; R ₁₂ is Arg or Lys; R ₁₃ is Ile or Val; R ₁₅ is Gly or D-Ala; R ₁₇ is Leu or D-Leu; R ₁₈ is Tyr or Ser; R ₂₄ is His or Gln; R ₂₅ is Gln, Asp, D-Glu or D-Asp; R ₂₇ is Met, D-Met, Ala, Nle, Ile, Leu, Nva or Val; R ₂₈ is Asn or Ser; R ₃₄ is Arg or Ser; R ₃₈ is Gln or Arg; R ₃₉ is Arg or Gly; R ₄₀ is Ser or Ala; R ₄₂ is Phe, Ala or Val; R ₄₃ is Asn or Arg; R ₄₄ is a natural amino acid. However, (a) R ₁ has C ^α Me or C ^α Me substituents, (b) R ₁₇ and R ₂₃ are D-Leu, or (c) R ₂₅ is either D-Glu or D-Asp and R Any or all residues between ₂₉ -R ₄₄ may be deleted. The method of claim 1, wherein R ₂₅ is D-Glu. The method of claim 1, wherein R ₂₅ is D-Asp. The method according to claim 1, 2 or 3, wherein R ₂₃ is D-Leu. The method of claim 1, wherein R ₁₇ is D-Leu. The method according to any one of claims 1 to 5, wherein R ₂₇ is D-Nle. The method of claim ₁ , wherein R ₁ has a C ^α Me or N ^α Me substituent. The compound of claim ¹ , wherein X ¹ is hydrogen or an α-amino protecting group; X ² is a protecting group for a penol hydroxyl group of hydrogen or Tyr; X ³ is hydrogen or a carboxyl group, a protecting group for Asp or Glu; X ⁴ is a protecting group for an alcoholic hydroxyl group of hydrogen or Thr; X ⁵ is a protecting group for an alcoholic hydroxyl group of hydrogen or Ser; X ⁶ is hydrogen or Arg is a protecting group for guanidino groups; X ⁷ is a protecting group for hydrogen or Lys branched amino group; X ₈ is hydrogen or a suitable side chain protecting group; X is a protecting group for imidazole nitrogen of hydrogen or His and X ⁹ is selected from OH, OCH ₃ , ester, amide, hydrazide, -O-CH ₂ -resin support and -NH-resin support The way of the bar. The compound of claim 8 wherein X ¹ is BOC; X ² is 2,6-dichlorobenzyl, X ³ is Bzl, X ⁴ is Bzl, X ⁵ is Bzl, X ⁶ is Tos, X ⁷ is 2-chlorobenzyloxy carbonyl and X ⁹ is- Method of bar which is O-CH ³ resin support. The compound according to claim 8, wherein X ¹ is BOC, X ² is 2,6-dichlorobenzyl, X ³ is Bzl, X ⁴ is Bzl, X ⁵ is Bzl, X ⁶ is Tos, X ⁷ is 2-chlorobenzyloxy The method of bar wherein carbonyl and X ⁹ are -NH-resin supports. ※ Note: The disclosure is based on the initial application.