Patent EP-0245662-A1 (EP)
Inventor: KOUGE KATSUSHIGE
IPC: C07K5/083
Filed: 1987-04-11
Abstract: This invention is characterized by synthesizing an active ester represented by the general formula
     using an active esterifying agent consisting of a sulfonium salt represented by the general formula
     and further reacting the above-said active ester with a nucleophilic agent represented by the general formula H-B-Y to produce an ester or amide represented by the general formula (W)d A-B-Y, 
     wherein A represents -CO-, -SO 2 -, >PO-, or >PS- groups; R, represents a hydrogen, an alkyl group, a halogen group, a nitro group, or an alkoxy group; R 2  and R 3 , which may be same or different, each represents an alkyl group; X⊖ represents an anion typified by a halogen ion, a perchloric acid ion, a hydrogensulfuric acid ion, a methylsulfuric acid ion, and a p-toluenesulfonic acid ion; for W and d, 
     when the above A is a divalent group, d is 1, and W represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an alkyl group of C 1 -C 5  substituted by 1-3 halogen atoms, a group
     (wherein R 4  and R 5 , which may be same or different, ead represents a hydrogen, a hydroxyl group, a mercapto group an alkyl group, or an aryl group; when Q is oxygen or sulfur, U is 0, and R e  represents a hydrogen, an alkyl group, an ary group, a cycloalkyl group, an alkenyl group, an alkynyl group or an aralkyl group; when Q is nitrogen, u is 1, and R 6  and R' 6 , which may be same or different, each represents a hydrogen, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, or an aralkyl group; and k represents an integral number of 1-4), an alkoxy group, a cycloalkoxy group, an aryl group, an aryloxy group, an aralkoxy group represented by
     (wherein Rn represents a hydrogen, a halogen atom, an alkyl group, an alkoxy group, an alkylthio group, an alkylsulfonyl group, an aryl group, or a group
     R 7  and R s , which may be same or different, each represents a hydrogen or an alkyl group; and m represents an integral number of 1-4), an isobonyloxy group, a furfuryloxy group, a fluorenylmethoxy group, or a group R 9 -R 10 N- (wherein R 9  and R 10 , which may be same or different, each represents a hydrogen, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, or an aralkyl group, or R 9  and R 10  may be combined each other to form a ring having 3-6 carbon atoms, when occasion demands, containing other hetero atoms), when the above A is particularly
     W may be an amino acid group in which a proper protective group is introduced or not Introduced in the α-amino group and/or the side chain together with W-Cl-, and/or a group or a peptide or protein, and 
     ②when the above A is a trivalent group, d is 2 and, in this case, two Ws, which may be same or different, each represents an alkoxy group, an alkenoxy group, an alkyl group, an aralkoxy group, an aryloxy group, an alkylamino group, an alkylthio group, or an aryl group; 
     B represents NR 11  (wherein R 11  represents a hydrogen, an alkyl group, an alkenyl group, an alkynyl group or an aryl groupl, oxygen, or sulfur ; and Y represents a group represented by
     (wherein Y represents a hdrogen, an alkyl group, a cycloalkyl group, a halogenoalkyl group, or an aryl group ; F represents NH, oxygen, sulfur alkylamino, or NHCO groups ; R 12  and R 13 , which may be same or different, each represents a hydrogen, HO-, HS-, an alkyl group, an alkylthio group, an alkylamino group, an alkenyl group, an alkynyl group, or an aryl group, q is 0 or 1 ; and r represents an integral number of 0-4), or H-B-Y is an amino acid in which a proper protective group is introduced or not introduced in the side chain and/or the α-carboxyl group, a peptide or protein in which a proper protective group is introduced or not introduced in the side chain and/or the terminal carboxyl group, or a glucide in which the hydroxyl group in the molecule is properly protected or not protected.