	US 7,531,506 B2
	Process for producing trunkamide a compounds
Fernando Albericio Palomera, Barcelona (Spain); Josep Maria Caba Naudi, Barcelona (Spain); Ernest Giralt Lledó, Barcelona (Spain); Ignacio Manzanares, Madrid (Spain); and Ignacio Rodriquez, Madrid (Spain)
Assigned to Pharma Mar, S.A., Madrid (Spain)
Appl. No. 10/473,096 PCT Filed Apr. 02, 2002, PCT No. PCT/GB02/01527 § 371(c)(1), (2), (4) Date Apr. 02, 2004, PCT Pub. No. WO02/081506, PCT Pub. Date Oct. 17, 2002.
Claims priority of application No. 0108234.6 (GB), filed on Apr. 02, 2001.
Prior Publication US 2005/0014684 A1, Jan. 20, 2005
Int. Cl. A61K 38/00 (2006.01); A61K 38/12 (2006.01)

U.S. Cl. 514—9 [530/317; 530/333]

30 Claims

1. A process for preparing a cycloheptapeptide containing a 5-membered heterocyclic ring as part of the backbone of the cyclic peptide, the cycloheptapeptide being of formula (III):

wherein Aaa₂, Aaa₃, Aaa₄, Aaa₅, and Aaa₆are independently α-amino acids of L or D configuration, if applies; wherein Aaa₁is independently an amino azole five member heterocyclic; wherein

X is O or S;

wherein Y is independently C or CH;

Z is CH or CH₂;

each of the dash lines indicates a permitted second bond, with the proviso that if the second bond exists between Y and the nitrogen atom bearing R_g, then R_gis absent;

R₁is a benzyl group;

R₂is selected from the group consisting of an alkyl group, an alkenyl group, and an aralkyl group and their substituted derivatives with an hydroxy group, a mercapto group, an amino group, a guanidino group, a halogeno group;

R₄is selected from the group consisting of an alkyl group, an alkenyl group, an aryl group, and aralkyl group and their substituted derivatives with an hydroxy group, a mercapto group, an amino group, a guanidino group, a halogeno group;

R₃and R₅are each independently selected from the group consisting of H or an alkyl group and its substituted derivatives with an hydroxy group, a mercapto group, an amino group, a guanidino group, a halogeno group;

R₆is 1-methylpropyl;

R₇is methyl;

R₈and R_fform a —CH₂CH₂CH₂— group;

and each of R_a, R_b, R_c, R_d, R_e, and R_gis H;

which process comprises synthezising by solid phase synthesis a linear heptapeptide precursor, the precursor either contains a heterocyclic ring or is able to form a heterocyclic ring;

cyclising the linear heptapeptide and if necessary forming the heterocyclic ring.