US 12,240,871 B2
Method for producing peptide compound
Hisayuki Takeuchi, Funabashi (JP); Yukio Asaka, Funabashi (JP); Akihiro Nagaya, Funabashi (JP); Michiharu Handa, Funabashi (JP); Keiichi Masuya, Kawasaki (JP); Tomonori Taguri, Kawasaki (JP); Yoshitaka Nemoto, Kawasaki (JP); Yutaka Kobayashi, Kawasaki (JP); Ayumu Matsuda, Kawasaki (JP); Haruaki Kurasaki, Kawasaki (JP); and Douglas Robert Cary, Kawasaki (JP)
Assigned to Nissan Chemical Corporation, Tokyo (JP); and PeptiDream Inc., Kawasaki (JP)
Appl. No. 17/439,601
Filed by NISSAN CHEMICAL CORPORATION, Tokyo (JP); and PeptiDream Inc., Kawasaki (JP)
PCT Filed Mar. 16, 2020, PCT No. PCT/JP2020/011420
§ 371(c)(1), (2) Date Sep. 15, 2021,
PCT Pub. No. WO2020/189621, PCT Pub. Date Sep. 24, 2020.
Claims priority of application No. 2019-048930 (JP), filed on Mar. 15, 2019.
Prior Publication US 2022/0153777 A1, May 19, 2022
Int. Cl. C07K 1/08 (2006.01); C07C 69/96 (2006.01)
CPC C07K 1/08 (2013.01) [C07C 69/96 (2013.01)] 20 Claims
 
1. A method for producing a peptide which comprises the following Steps (1) to (3):
(1) a step of mixing an N-terminal protected amino acid or an N-terminal protected peptide represented by the formula (I) P-A1-OH
wherein P is an N-terminal protective group, and A1 represents a group derived from an amino acid, a group derived from an N—C1-6 alkylamino acid, where the C1-6 alkyl may have a substituent(s), or a group derived from a peptide,
with an activating agent represented by the formula (II)

OG Complex Work Unit Chemistry
wherein X represents a halogen atom, and R1 represents a secondary C5-40 alkyl group which may have a substituent(s);
(2) a step of mixing an amino acid or a peptide represented by the formula (IV): H-A2-OH
wherein A2 represents a group derived from an N—C1-6 alkylamino acid, where the C1-6 alkyl may have a substituent(s), or a group derived from a 4- to 6-membered cyclic secondary amino acid, where the 4- to 6-membered ring may be fused with a cyclic compound selected from the group consisting of a C6-14 aryl ring, a C6-14 haloaryl ring and a C3-8 cycloalkyl ring, or a group derived from a peptide in which the N-terminal residue is an N—C1-6 alkylamino acid, where the C1-6 alkyl may have a substituent(s), or a 4- to 6-membered cyclic secondary amino acid, where the 4- to 6-membered ring may be fused with a cyclic compound selected from the group consisting of a C6-14 aryl ring, a C6-14 haloaryl ring and a C3-8 cycloalkyl ring,
with a silylating agent; and
(3) a step of mixing a product obtained in Step (1) and a product obtained in Step (2).