Cyclic RGD peptide and method for preparing the same

Patent metadata

Field	Value
Publication number	US-11485756-B2
Application number	US-202016860687-A
Country	US
Kind code	B2
Filing date	Apr 28, 2020
Priority date	Jan 16, 2020
Publication date	Nov 1, 2022
Grant date	Nov 1, 2022

Abstract

A method for preparing a cyclopeptide and a cyclopeptide preparing by the method are disclosed. The method includes the following steps: (A) providing compounds represented by the following formulas (I-1) and (I-2):wherein, G, Ra, Rb, Rc, Rd, and Re are defined in the specification; (B) performing a reaction between the compounds of formulas (I-1) and (I-2) to obtain a compound represented by the following formula (I-3):and (C) performing a cyclization reaction of the compound of formula (I-3) with a catalyst of formula (II) and deprotection to obtain a compound represented by the following formula (III):wherein, G′, Q, M, L1, L2, m, y, and z are defined in the specification.

First claim

What is claimed is:

1. A method for preparing a cyclopeptide, comprising the following steps:
(A) providing compounds represented by the following formulas (I-1) and (I-2):

wherein, R a , R b and R e are each independently a protection group;
R c and R d are each independently alkyl, cycloalkyl, aryl or heteroaryl;
G is H, or O-t-Bu; and
R 1 is

in which R 2 and R 3 are each independently H or C 1-6 alkyl; X is O, S, CH 2 , or N—R 4 , in which R 4 is H, C 1-6 alkyl, (CH 2 CH 2 O) n H, —C(═O)—C 1-15 alkyl, —C(═O)CH 2 (OC 2 H 4 ) n OR′ or C(═O)(C 2 H 4 ) 2 C(═O)O(C 2 H 4 O) n R′, in which n=1-3 and R′ is H or CH 3 ;
(B) performing a reaction between the compounds of formulas (I-1) and (I-2) to obtain a compound represented by the following formula (I-3):

and
(C) performing a cyclization reaction of the compound of formula (I-3) with a catalyst of formula (II) and deprotection to obtain a compound represented by the following formula (III):
M(O) m L 1 y L 2 z   (II)

wherein G′ is H or OH;
Q is halogen, OC(O)CF 3 or OC(O)CH 3 ;
M is a metal selected from the group consisting of IVB, VB, VIB and actinide groups;
L 1 and L 2 respectively is a ligand;
m and y are integers greater than or equal to 1; and
z is an integer greater than or equal to 0.

2. The method of claim 1 , wherein L 1 is selected from the group consisting of Cl, OTf, OTs, NTf 2 , halogen, RC(O)CH 2 C(O)R, OAc, OC(O)CF 3 , OEt, O-iPr and O-t-butyl, in which R is alkyl.

3. The method of claim 1 , wherein L 2 is selected from the group consisting of Cl, H 2 O, CH 3 OH, EtOH, THF, CH 3 CN, and

4. The method of claim 1 , wherein R a and R e are fluorenylmethyloxycarbonyl, and R b is 2,3,6-trimethyl-4-methoxylbenzenesulphonyl.

5. The method of claim 1 , wherein M is a group IVB transition element, m is 1 and y is 2.

6. The method of claim 1 , wherein M is a group VB transition element, m is 1 and y is 2 or 3.

7. The method of claim 1 , wherein M is a group VIB transition element, m is 1 and y is 4.

8. The method of claim 1 , wherein M is a group VIB transition element, m is 2 and y is 2.

9. The method of claim 1 , wherein M is selected from the actinide group, m is 2 and y is 2.

10. The method of claim 1 , wherein the catalyst of formula (II) is MoO 2 Cl 2 , V(O)Cl 2 , V(O)(OAc) 2 , V(O)(O 2 CCF 3 ) 2 , Ti(O)(acac) 2 , Zr(O)Cl 2 , Hf(O)Cl 2 , Nb(O)Cl 2 , MoO 2 (acac) 2 , V(O)(OTs) 2 , VO(OTf) 2 , or V(O)(NTf 2 ) 2 .

11. The method of claim 1 , wherein z is 0.

12. The method of claim 1 , wherein the compound of formula (III) is any one of formulas (III-1) to (III-5):

wherein R 5 is C 1-15 alkyl.

Assignees

• Univ Nat Tsing Hua

Inventors

• Chen Chien-Tien
• Weng Shiue-Shien

Classifications

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07K7/64 Primary

  Cyclic peptides containing only normal peptide links · CPC title

• C07K5/123 Primary

  Tripeptides · CPC title

• C07K5/12

  Cyclic peptides {with only normal peptide bonds in the ring} · CPC title