US 12,258,422 B2
Cyclopeptide and method for preparing the same
Chien-Tien Chen, Hsinchu (TW); and Shiue-Shien Weng, Hsinchu (TW)
Assigned to NATIONAL TSING HUA UNIVERSITY, Hsinchu (TW)
Filed by NATIONAL TSING HUA UNIVERSITY, Hsinchu (TW)
Filed on Jul. 14, 2022, as Appl. No. 17/864,829.
Application 17/864,829 is a division of application No. 16/860,687, filed on Apr. 28, 2020, granted, now 11,485,756.
Claims priority of application No. 109101475 (TW), filed on Jan. 16, 2020.
Prior Publication US 2022/0372073 A1, Nov. 24, 2022
Int. Cl. C07K 5/12 (2006.01); C07K 7/64 (2006.01)
CPC C07K 5/123 (2013.01) [C07K 7/64 (2013.01)] 12 Claims
 
1. A method for preparing a cyclopeptide, comprising the following steps:
(a) providing compounds represented by the following formulas (I-1) and (I-4):

OG Complex Work Unit Chemistry
wherein, Ra, Rb and Re are each independently a protection group;
Rc and Rd are each independently alkyl, cycloalkyl, aryl or heteroaryl;
G is H or O-t-Bu; and
R1 is

OG Complex Work Unit Chemistry
in which R2 and R3 are each independently H or C1-6 alkyl; X is O, S, CH2, or N—R4, in which R4 is H, C1-6 alkyl, (CH2CH2O)nH, —C(═O)—C1-15 alkyl, —C(═O)CH2(OC2H4)nOR′ or C(═O)(C2H4)2C(═O)O(C2H4O)nR′, in which n=1-3 and R′ is H or CH3;
(b) performing a reaction between the compounds of formulas (I-1) and (I-4) to obtain a compound represented by the following formula (I-5):

OG Complex Work Unit Chemistry
(c) performing a reaction between the compound of formula (I-5) and the compound represented by the following formula (I-6) to obtain a compound represented by the following formula (I-7):

OG Complex Work Unit Chemistry
wherein Rf is alkyl, cycloalkyl, aryl, or heteroaryl; and
(d) performing a cyclization reaction of the compound of formula (I-7) with a catalyst of formula (II) and deprotection to obtain a compound represented by the following formula (III):

OG Complex Work Unit Chemistry
M(O)mL1yL2z  (II)
wherein G′ is H or OH;
Q is halogen, OC(O)CF3, or OC(O)CH3;
M is a metal selected from the group consisting of IVB, VB, VIB and actinide groups;
L1 and L2 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.