ABSTRACT
A concise synthesis of a highly functionalized intermediate lacking only C10 of the mitomycin backbone is described. The key to this development is the Brønsted acid-catalyzed aza-Darzens reaction used to forge the cis-aziridine. Additionally an oxidative ketalization fortuitously occurs during the quinone-enamine coupling step, leading to an orthogonally protected hydroquinone.
Subject(s)
Antibiotics, Antineoplastic/chemical synthesis , Aziridines/chemical synthesis , Mitomycin/chemical synthesis , Antibiotics, Antineoplastic/chemistry , Aziridines/chemistry , Catalysis , Crystallography, X-Ray , Mitomycin/chemistry , Models, Molecular , StereoisomerismABSTRACT
[Structure: see text] An advanced intermediate in our planned synthesis of mitomycin C has been acquired in nine steps from tert-butyl glyoxylate. The aziridinyl pyrrolidine and quinone subunits are coupled regioselectively to arrive at an enamine that is prepared for C10 homologation.
Subject(s)
Biological Products/chemical synthesis , Mitomycin/chemical synthesisABSTRACT
A mild protocol for the synthesis of cis-aziridines is described that employs a catalytic amount of Brønsted acid. Despite the potential for diazo compound decomposition via alkylation or homocoupling upon exposure to a proton source, these pathways are slow relative to [2 + 1] annulation in the presence of a Schiff base, leading to aziridine product. The process uses no metals or reagents that must be removed chromatographically, exhibits rapid turnover rates, and produces only atomic nitrogen as a coproduct. High levels of relative stereocontrol are also possible when forming the Schiff base from a chiral nonracemic aldehyde.
ABSTRACT
[reaction: see text] The first examples of free radical-mediated vinyl amination are described by nonconventional vinyl radical addition to azomethine nitrogen. This new vinyl amination protocol is mild and provides convenient synthetic access to nonstabilized N,N-dialkyl enamines and tandem bond-forming processes.
