The derivation of 1a-demethylmitomycin G from mitomycin C.
Mitomycin G (2) was derived from porfiromycin (10b) in 3 steps via the methanesulfonate (14b) in an overall yield of 39%. On the basis of the established method for the introduction of an exomethylene group in mitomycins with a 9a-methoxy group, the preparation of biologically more important 1a-demethylmitomycin G (5) from mitomycin C (1) was accomplished by the use of a protective acetyl group on the aziridine in an overall yield of 57%. 1a-Demethylmitomycin K (6) was obtained from 5 in a yield of 42%. In a preliminary evaluation of their antitumor activity, compound 5 showed superior activity against sarcoma 180 (sc-ip) to its 1a-methyl congener, i.e., mitomycin G (2).
Kono
M
M
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Kasai
M
M
Shirahata
K
K
Morimoto
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000138:chemical synthesis* / Q000627:therapeutic use; D015394:Molecular Structure; D012510:Sarcoma 180 / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; D016685:Mitomycin; C064493:1a-demethylmitomycin G