BCH-2763

Chemical Name: 5-[5-[5-(D-Phenylalanyl-L-propyl-L-arginyl)pentanamido]pentanamido]pentanoyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-prolyl-L-isoleucyl-L-prolyl-L-leucine; D-Phenylalanyl-L-propyl-7(S)-amino-10-guanidino-6-oxodecanoyl-5-aminopentanoyl-5-aminopentanoyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-prolyl-L-isoleucyl-L-prolyl-L-leucine
CAS No. 183968-56-1
项目整合开发状态: Preclinical
项目研究机构: National Research Council of Canada (Originator), Shire BioChem (Codevelopment)
合成路线:Nalpha-Boc-Ngamma-tosyl-L-arginine (I) was converted to the N,O-dimethyl hydroxamate (II) by treatment with dimethylhydroxylamine and BOP.Condensation of (II) with the Grignard reagent (IV),prepared from 6-bromo-1-hexene (III),produced ketone (V).Then,oxidative cleavage of the terminal alkene of (V) by means of NaIO4 and RuCl3 yielded carboxylic acid (VI).

合成路线:Solid-phase peptide synthesis started with N-Boc-L-leucine linked to a PAM resin (VII).Deprotection of the Boc group was effected by treatment with trifluoroacetic acid in CH2Cl2 to give leucine-resin (VIII).Sequential couplings with the respective protected amino acids were mediated by DCC and HOBt,and trifluoroacetic acid in CH2Cl2 was used for deprotection of the Boc groups.The following protected amino acids were sequentially coupled: N-Boc-L-proline (IX),N-Boc-L-isoleucine (XI),N-Boc-L-proline (IX),N-Boc-L-glutamic acid omega-benzyl ester (XIV),N-Boc-L-phenylalanine (XVI) and N-Boc-L-aspartic acid omega-cyclohexyl ester (XVIII) to afford the peptide resins (X),(XII),(XIII),(XV),(XVII) and (XIX),respectively.

合成路线:Then,two sequential couplings with N-Boc-5-aminopentanoic acid (XX),followed by deprotections with trifluoroacetic acid in the presence of ethyl methyl sulfide,provided peptide resins (XXI) and (XXII).

合成路线:Amino acid (VI) was then coupled to the peptide sequence to provide,after trifluoroacetic acid deprotection,resin (XXIII).The terminal D-Phe and L-Pro residues were incorporated as the preformed dipeptide (XXIV).Finally,cleavage of all protecting groups by means of HF in the presence of dimethyl sulfide and anisole furnished the title compound.