title: Effective asymmetric synthesis of 1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI).
abstract: A short, asymmetric synthesis of the 1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI) analogue of the CC-1065 and duocarmycin alkylation subunits is detailed that employs an effective enzymatic desymmetrization reaction of prochiral diol 12 using a commercially available Pseudomonas sp. lipase. The optically active monoacetate (S)-13 is furnished in exceptional conversions (88%) and optical purity (99% ee) and serves as an intermediate for the preparation of either enantiomer of CBI. Similarly, the Pseudomonas sp. lipase resolved the racemic intermediate 19, affording advanced intermediates of CBI in good conversions and optical purity (99% ee), and provided an alternative approach to the preparation of optically active CBI derivatives.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Kastrinsky
authors.forename: Dale L
authors.initials: DL
authors.lastname: Boger
mesh_terms: D000478:Alkylation; D000903:Antibiotics, Antineoplastic / Q000032:analysis / Q000138:chemical synthesis*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003521:Cyclopropanes / Q000032:analysis / Q000138:chemical synthesis*; D000080890:Duocarmycins; D007211:Indoles / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry*; D008049:Lipase / Q000378:metabolism; D015394:Molecular Structure; D011549:Pseudomonas / Q000201:enzymology; D013237:Stereoisomerism
chemical_list: C445728:1,2,9,9a-tetrahydrocyclopropa(c)benz(e)indol-4-one; D000903:Antibiotics, Antineoplastic; D003521:Cyclopropanes; D000080890:Duocarmycins; D007211:Indoles; C018782:CC 1065; D008049:Lipase