Study On The Synthesis Of Anti-tumor Antibiotic C-1027 Chromophore Enediyne Unit

C-1027 discovered first by our institute is a new macromolecular antitumor antibiotis,produced by Stereptomyces globisporus C-1027.Its molecule is composed of an enediyne chromophore and an apoprotein through non-covalent bond binding and the chromophore embodys the whole molecular activity against tumors.C-1027 inhibits mainly DNA synthesis and shows extremely potent cytotoxicity to cultured cancer cell,and is one of the most potent of the macromoleculor antitumor antibiotics ever reported.Our study was set to persuit for synthesis of 9-membered ring enediyne and 10-membered ring enediyne of C-1027-Chr,and some acyclic enediynes in order to leam the stniture-activity relationslup of this new compound and give a help to further study or modulate them.To synthesize 9-membered ring enediyne conjugated with cyclopantene of C-1027-Chr,We had tried here and there four routs,finally starting from dimer of cyclopantandiene 9. We have gotten ene-yne compound 40 through 9 steps. 40 reacted with iodo instituted ene-yne 47,prepared from BrCH₂COCC₂H₅ and PPh₃ through 5 steps,to give the crucial intermidate 48.After removed triethylsilyl group it yield the desired acyclic 9-memdered ring enediyne 49.Sereal general methods were applied to cyclizate,but no success.To learn more structure-activity relationship,we tried to enlarged 9-membered ring of enediyne of C-1027-Chr to 10-membered ring. So,from helo-cyclopantenone 12(or 35),through 5 steps,we got ene-yne-one compound 76,which reacted with iodo substituted ene-yne compound to give the desired acyclic 10-membered ring enediyne compound 77.Its cyclization is being carried on.In our study here,we designed a new approach to prepare a series of iodo...