Patent GB-1250361-A (GB)
IPC: C07K14/585
Filed: 1969-04-11
Abstract: 1,250,361. Thyrocalcitonins. AMERICAN CYANAMID CO. 11 April, 1969 [8 May, 1968; 4 Sept., 1968], No. 18812/69. Heading C2C. A compound of the formula - Cys - Ser - Asx - Leu - Ser - Thr - Cys - Val- Leu - Ser - Ala - Tyr - Try - Arg - Asx - Leu- (Asx) l (Asx) m  - (Phe) n  - (His) o  - (Arg) p  - (Phe)q- (Ser), - (Gly) s  - (Met) t  - (Gly) u  - (Phe) v  - (Gly) w - (Pro) x -(Glx) y -(Thi) z - where the N-terminal group of the peptide is a group completing an amine group or a functional derivative thereof, the C-terminal of the peptide is a group completing a carboxyl group or a functional derivative thereof and each S- represents a blocked mercapto forming part of the cysteine residue or when taken together represents an -SS- linkage of a cystinyl residue and wherein the subscripts l to z are 0 or 1 with the proviso that when a subscript is 0, the or each subsequent subscript in the amino acid sequence is also 0 whereby the amino acid sequence of the peptide is the dashes conventionally representing bonds connecting amino acids or attached to groups thereon, is prepared condensing smaller units or amino acids together to form the peptide in known manner. The following compounds are prepared as starting materials or intermediates, BOC - Val- LeuONB, BOG - Val - LeuOH, H - Val - LeuOH, TFA; BOC - Cys(SBzl) - Val - Leu - OH, HCys(SBzl) - Val - LeuOH, TFA; BOC - Thr- Cys(SBzl) - Val - LeuOH; HThr - Cys(SBzl) -  Val - LeuOH, TFA; BOC - Ser(OBzl) - Thr- Cys{SBzl) - Val - LeuOH, HSer - (OBzl) - Thr- Cys(SBzl) - Val - Leu - OH, TFA; BOC - Asn- Leu - ONB; BOC - Asn - LeuOH; HAsn- Leu - OH, TFA; BOC - Ser(OBzl) - Asn- LeuOH ; H - Sw(OBzl) - Asn - LeuOH ; BOC - Cys(SBzl) - Ser(OBzl) - Asn - LeuOH; BOC - Cys(SBzl) - Ser(OBzl) - Asn - LeuOSu; (Z)His - Arg(NO 2 ) - OMe; Z-His - Arg(NO 2 )OH; Z - His - Arg - (N0 2 )Phe - ONB; H . His- Arg(NO 2 ) - Phe - ONB and its HBr salts; BOC - Asn - Phe - ONB; HAsn - PheONB, HCl; BOC - Asn - Asn - Phe - ONB; BOCAsn - Asn - Phe - OH; BOC - Asn - Asn- Phe - OSu; BOC - Asn - Leu - ONB; H - Asn- Leu - ONB TFA; BOC - Arg(NO 2 ) - Asn - Leu- ONB; BOC - Arg(N0 2 ) - Asn - LeuOH; BOCArg(N0 2 ) - Asn - LeuOSu; BOC - Arg(N0 2 ). Asn - Leu - NH 2 ; H - Arg(N0 2 ) - Asn - LeuNH 2  TFA; BOC - Tyr - TryOH; HTyr - TryOH; BOC - Ala - Tyr - Try - OH; H - Ala - Tyr- TryOH ACT ; BOC - Ser(OBzl) - Ala - Tyr - Try- OH; BOC - Ala - TyrONB; H - Ala - Tyr- ONB - HCl; BOC - Ser - Ala - Tyr - ONB; BOC - Ser - Ala - TyrOH; BOC - Ser(OBzl}- GlyOMe; BOC - Ser(OBzl) - GlyOH; BOCSer(OBzl).- Gly - MetOMe; BOC - Ser(OBzl)- Gly - MetOH; BOC - Ser(OBzl) - Gly - Met - NH 2 ; H - Ser(OBzl) - Gly - MetNH 2 TFA; Z - Gly- Phe - Gly - Pro - OtBu; H - Gly - Phe - Gly- Pro - OtBu, HCl; BOG - Gly - Met - Gly - Phe- Gly - Pro - OtBu; H - Gly - Met - Gly - Phe- Gly - ProOH, HCl; BOG - Ser(OBzl) - Gly- Met - Gly - Phe - Gly - ProNH a , H - Ser(OBzl)- Gly - Met - Gly - Phe - Gly - Pro - NH 2 HCl; BOCSer(OBzl) - Ala - Tyr - Try - Arg(N0 2 )- Asn - Leu - NH 2 ; H - Ser(OBzl) - Ala - Tyr- Try - Arg(NO 2 ) - Asn - LeuNH 2 , TFA; BOCSer(OBzl) - Thr - Cys - (SBzl) - Val - Leu - Ser- (OBzl) - Ala - Tyr - Try - Arg(NO 2 ) - Asn - Leu- NH 2 ; and the N - unprotected peptide; BOCCys(SBzl) - SerO(Bzl} - Asn - Leu - Ser(OBzl)- Thr - Gys(SBzl) - Val - Leu - Ser(OBzl) - Ala- Tyr - Try - Arg(N0 2 ) - Asn - LeuNH 2  and the N- and 0-unprotected peptide hydrofluoride; BOC - Ser(OBzl) - Thr - Cys(SBzl) - Val - Leu- Ser - Ala - Tyr - Try - Arg(N0 2 ) - Asn - Leu- Asn-Asn-Asn-Phe-His-Arg(NO 2 )-Phe-ONB and the N-unprotected peptide; BOG - Gys(SBzl)- Ser(OBzl) - Asn - Leu - SerOBzl Thr - Cys{SBzl)- Val - Leu - Ser - Ala - Tyr - Try - Arg(N0 2 )- Asn - Leu - Asn - Asn - Phe - His - Arg(NO 2 )- Phe - ONB; and its amide and the N-unprotected peptide; BOG - Asn - Asn - Phe - His- Arg(N0 2 ) - Phe - ONB and the N-unprotected peptide; BOO - Arg(NO 2 ) - Asn - Leu - Asn- Asn - Phe - His - Arg(N0 2 ) - Phe - ONB and the unprotected peptide; BOO - Try - Arg(N0 2 )- Asn - Leu - Asn - Asn - Phe - His - Arg(N0 2 )- PheONB and the N-unprotected peptide; BOCSer - Ala - Tyr - Try - Arg(NO 2 ) - Asn - Leu- Asn - Asn - Phe - His - Arg(NO 2 ) - Phe - His- Arg(N0 2 ) - Phe - ONB, and the free acid; BOG - Ser - Ala - Tyr - Try - Arg(N0 2 ) - Aan- Leu - Asn - Asn - Phe - His - Arg(N0 2 ) - Phe- Ser(OBzl) - Gly - Met - NH 2  and the N-unprotected peptide; BOG - Cys(SBzl)Ser{OBzl)- Asn - Leu - Ser(OBzl) - Thr - Cys(SBzl} - Val- Leu - OH; BOG - Cys(SBzl) - Ser(OBzl) - Asn- Leu - Ser(OBzl) - Thr - Cye(SBzl) - Val - Leu- Ser - Ala - Tyr - Try - Arg(N0 2 )Am - Leu- Asn - Asn - Phe - His - Arg(N0 2 ) - Phe - Ser- (OBzl) - Gly - Met - NH 2  and the N- and 0- unprotected peptides, BOG - Ser - Ala - Tyr- Try - Arg(N0 2 ) - Asn - Leu - Asn - Asn - Phe- His - Arg(N0 2 ) - Phe - 8er(OBzl) - Gly - Met- Gly - Phe - Gly - ProNH 2  and the N-unprotected peptide; BOC - Ser(OBzl) - Thr - Cys- (SBzl) - Val - Leu - Ser - Ala - Tyr - Try - Arg- (N0 2 ) - Asn - Leu - Asn - Asn - Phe - His- Arg(N0 2 ) - Phe - Ser(OBzl) - Gly - Met - Gly- Phe - Gly - ProNH 2  and the N-unprotected peptides, and BOG - Cys(SBzl) - Ser(OBzl)- Asn - Leu - Ser(OBzl) - Thr - Cys(SBzl) - Val- Leu - Ser - Ala - Tyr - Try - Arg(N0 2 ) - Asn- Leu - Asn - Asn - Phe - His - Arg(N0 2 ) - Phe- Ser(OBzl) - Gly - Met - Gly - Phe - Gly - ProNH 2  and the 0- and N-unprotected peptide.