Mitomycin rearrangement

A total synthesis of ( + )-mitomycins via isomitomycin A is described (87JA7881), and from a mitomycin rearrangement albomitomycin A and isomitomycin A were formed from mitomycin A (87JA7224). Amidine derivatives were prepared from mitomycin C and formamide acetals. These, when treated with amines, afforded the corresponding 7-N-substituted mitosanes (87JOC5601). 

Other ring contractions that give azapentalene derivatives include the rearrangement of a fused oxazine to a pyrazolo[l,5-a]indol-4-one with acetic anhydride,165 and an interesting photochemical contraction of a cyclic lactone, which produces an isomeric fused indolone by a mechanism thought to involve the first meta photo-Fries rearrangement [Eq. (19)].166 The product was used as an intermediate for the synthesis of mitomycin antibiotics (Section VI,A). 

Mitomycin C forms a weak association with metal ions and these metal complexes undergo rearrangement to mitosenes in methanol (86JMC144). Complexes were also tested for antitumor activity (86JMC1760). 

This method has also been used as a key step in the synthesis of ( )-stigmolone,214 coupled to an oxyCope rearrangement for the preparation of seven- or eight-membered carbocycles215 and used as a key step in the synthesis of mitomycin alkaloids.216 Another variant of the procedure has been developed for the cleavage of allyl ethers to yield alcohols.217... 

If any one of the three natural products denoted below (isomitomycin A, albomitomycin A, or mitomycin A) is simply dissolved in an alcohol solvent like methanol, it will rearrange into an equilibrium mixture that contains the other two materials the favored compound is mitomycin A. The process for that equilibration is a series of Michael reactions and retro-Michael reactions as shown. All are potent compounds, but it is their ability to rearrange through such chemistry that is equally remarkablel... 

Danishefsky et al. developed a stereospedfic route for the synthesis of deoxy analog of mitomycin via an aromatic Claisen rearrangement [84]. The aUyl aryl ether 112 was prepared from allylic alcohols and phenol derivative via the Mitsu-nobu reaction. The aromatic Claisen rearrangement of 1,3-disubstituted aUyhc ether 112 proceeded under thermal conditions (N,N-dimethylaniline reflux) to afford the ortho rearrangement product 113 in 80% yield. 

The neoplasm inhibitors, isomitomycin A (52) and albomitomycin A (54) and (56), were isolated, together with mitomycin A from S. caespitosus culture broth. Both antibiotics were obtained by intramolecular rearrangement of mitomycin A [76]. Anticancer antibiotics AX-2 (53) and CX-1 (55) were isolated from the culture broth of S. caespitosus and obtained from mitomycin C [77]. Other biological activities of different mitomycines, their mechanisms of action, and therapeutic utility have been described in various reviews [5, 9, 77-83]. 

The photo-Fries rearrangement has been used in various synthetic reactions. A recent application concerned the synthesis of the mitomycin precursor (148) in high yield from the lactone (147). Finally, reference is made to the efficient photochemical deconjugation of piperidine esters (149) to the endocyclic isomers (150), presumably by a photoenolization reaction. ... 

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