Enantioselective Synthesis of an Aziridinomitosane and Selective Functionalizations of a Key Intermediate

• Published in: Journal of organic chemistry Vol. 68; no. 7; pp. 2728 - 2734
• Main Authors: Papaioannou, Nikolaos, Blank, Jarred T, Miller, Scott J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.04.2003; Amer Chemical Soc
• Subjects: Catalysis; Chemistry; Chemistry, Organic; Chemistry, Organic - methods; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Indicators and Reagents; Isatin - chemistry; Mitomycin - chemical synthesis; Mitomycin - chemistry; Mitomycins; Molecular Structure; Organic chemistry; Peptides - chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; ENANTIOMERIC PAIR; ALCOHOLS; METHOXY-N-METHYLAMIDES; FR900482; RING-CLOSING METATHESIS; KINETIC RESOLUTION; MITOMYCIN-C; OLEFIN METATHESIS; COMPLETION; CATALYSTS; Cyclization; Enantioselectivity; Nitrogen heterocycle; Metathesis; Bicyclic compound; Alcohol; Aziridine derivatives; Tetracyclic compound; Oxygen heterocycle; Chemical synthesis; Ketone
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0269013

An enantioselective synthesis of mitosane core (−)-1 has been achieved. Key steps include a rapid assembly of a key eight-membered-ring intermediate employing ring-closing metathesis. Kinetic resolution of an advanced secondary alcohol was then accomplished by using a peptide-based asymmetric acyl transfer catalyst that was discovered from a parallel screen of catalyst candidates. Optically pure material was then converted to the mitosane core, which was the subject of additional studies on the selective modification to produce several substituted compounds containing a mitosane ring system.