Enantiodivergent synthesis of either enantiomer of ABCDE-ring analogue of antitumor antibiotic fredericamycin A via intramolecular [4 + 2] cycloaddition approach.
[reaction: see text] An intramolecular enantiodivergent synthesis of both enantiomers of the ABCDE-ring analogue 22 of fredericamycin A is reported. Key steps involve an intramolecular [4 + 2] cycloaddition of 17 and an aromatic Pummerer-type reaction of 19. A lipase-catalyzed enantioselective desymmetrization of prochiral diol 2 using 1-ethoxyvinyl 2-furoate 3 led to the pivotal intermediate (R)-4.
Akai
S
S
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka 565-0871, Japan.
Tsujino
T
T
Fukuda
N
N
Iio
K
K
Takeda
Y
Y
Kawaguchi Ki
K
K
Naka
T
T
Higuchi
K
K
Kita
Y
Y
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry*; D002175:Candida / Q000201:enzymology; D002942:Circular Dichroism; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry*; D008049:Lipase / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; D013141:Spiro Compounds; D008049:Lipase; C016660:fredericamycin A