26909-37-5Relevant articles and documents
C(10) halogen 10-des(carbamoyloxy)porfiromycins: Synthesis, chemistry, and biological activity
Choi,Yoo,Colson,Martin,Kohn
, p. 3391 - 3396 (1995)
An efficient four-step procedure for the preparation of C(10) halogen 10-des(carbamoyloxy)porfiromycins 3-5 beginning with mitomycin C(1) is described. Solvolytic removal (NaOMe, MeOH/benzene) of the C(10) carbamoyl group in 1 followed by N-methylation (dimethyl sulfate (15 equiv), 1,8-bis(dimethylamino)naphthalene (15 equiv) in THF) provided 10-decarbamoylporfiromycin (7) in 65% yield. Treatment of 7 with methanesulfonyl chloride in pyridine gave 10-decarbamoyl-10-methanesulfonylporfiromycin (8) in 83% yield, which upon heating with metal halides (i.e., LiCl, LiBr, NaI) in either DMF or ethylene glycol dimethyl ether furnished the C(10) halogen 10-des(carbamoyloxy)porfiromycins 3-5 in 68-81% yields. The C(10) halogen 10-des(carbamoyloxy)porfiromycins served as useful starting materials for C(10)-modified derivatives. Treatment of the C(10) bromo derivative 4 with 1,8-diazabicyclo[5.4.0]undec-7-ene provided the elimination product, 10-des(carbamoyloxy)-9-dehydroporfiromycin (12), while addition of AgSCN to the C(10) iodo porfiromycin 5 led to the substituted adducts 10-des(carbamoyloxy)-10-thiocyanatoporfiromycin (10) and 10-des(carbamoyloxy)-10-thiocyanato-9-epi-mitomycin D (11). The C(10) halogen 10-des(carbamoyloxy)porfiromycins also underwent novel radical and thermal skeletal rearrangements. Treatment of the C(10) iodo derivative 5 with tributyltin hydride and A1BN led to the production of the ring-expanded quinone 14. Thermolysis of the C(10) bromo (4) and the C(10) iodo (5) adducts gave the tetracycles 18 and 19, respectively, in which the C(2) nitrogen bond in the starting porfiromycin had been preferentially cleaved in favor of the C(1) bond. Potential pathways for these rearrangements are briefly outlined. The in vitro cytotoxicities of 3-5 in human colon carcinoma cell lines were evaluated. All three C(10) halogen 10-des(carbamoyloxy)porfiromycins were noticeably less potent than mitomycin C.
Synthesis of an oligodeoxyribonucleotide adduct of mitomycin C by the postoligomerization method via a triamino mitosene
Champeil, Elise,Paz, Manuel M.,Ladwa, Sweta,Clement, Cristina C.,Zatorski, Andrzej,Tomasz, Maria
scheme or table, p. 9556 - 9565 (2009/02/02)
The cancer chemotherapeutic agent mitomycin C (MC) alkylates and cross-links DNA monofunctionally and bifunctionally in vivo and in vitro, forming six major MC-deoxyguanosine adducts of known structures. The synthesis of one of the monoadducts (8) by the
Lack of Influence of the Carbamoyl Group on the Stereochemistry of the Acid-Catalyzed Opening of the Aziridine Ring of the Mitomycins and of Congeners
Hornemann, Ulfert,Keller, Paul J.,Takeda, Kazuyoshi
, p. 31 - 36 (2007/10/02)
The acid-catalyzed opening of the aziridine ring of mitomycins A and C is known to occur predominantly with cis stereochemistry.We have observed that the presence or absence of a carbamoyl group at C-10 of mitomycin C and in certain of its analogues does not have a significant influence on the stereochemistry of the opening of this ring.The trans product obtained from mitomycin C was shown to be stable when treated with acid under the conditions of its formation.Mitomycin B was also shown to yield predominantly the cis product when it was subjected to acid-catalyzedopening of its aziridine ring.The 1H NMR spectra of acetate derivatives prepared from mitomycin B show two sets of signals that are due to two populations of rotamers.The analysis of these spectra has substantiated several previous spectral assignments.This paper also presents some thoughts on acid-catalyzed bifunctional DNA alkylation by mitomycins and 10-decarbamoyloxy-9-dehydromitomycins.
