Enantioselective total synthesis of a potent antitumor antibiotic, fredericamycin A.
The asymmetric total synthesis of both enantiomers of the potent antitumor antibiotic fredericamycin A (1) is detailed based on the protocol for the construction of its peri-hydroxy polyaromatic skeleton bearing the chirality at the spiro carbon via a strong base-induced cycloaddition of suitably substituted homophthalic anhydrides (AB-ring unit) with an optically active CDEF-ring unit. Particular attention has been given to the novel synthesis of the optically active spiro carbon center by a stereospecific rearrangement of optically active benzofuzed-trans-epoxy acylates leading to spirocyclopentane-1,1'-indane systems. This method is quite useful for the construction of an optically active spiro compound and was applied to the synthesis of the optically pure CDEF-ring unit of 1. Cycloaddition of the optically pure CDEF-ring unit to AB-ring units prepared via benzyne afforded two natural and unnatural-type hexacyclic compounds, which were converted to natural and unnatural enantiomers of synthetic 1, and the absolute configuration of natural 1 was determined as S.
Kita
Y
Y
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Higuchi
K
K
Yoshida
Y
Y
Iio
K
K
Kitagaki
S
S
Ueda
K
K
Akai
S
S
Fujioka
H
H
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D007546:Isoquinolines / Q000138:chemical synthesis*; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; D013141:Spiro Compounds; C016660:fredericamycin A