39 ネオオキサゾロマイシンの全合成(口頭発表の部)
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概要
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The enantioselective total synthesis of neooxazolomycin (1), structurally novel antitumor agent, was achieved by utilizing newly developed several synthetic methods. For the construction of the fused bicyclic lactam-lactone terminus of (1), a novel dianion cyclocondensation was found. Thus, the reaction of the dianion 3 with the ester 6 furnished the β-hydroxylactams 7 and 7 in a 1:1.4 ratio. Treatment of 7 with acidic condition brought about diastereoselective lactonization to give 8, which was converted into 15 via selective reduction of its ester group. Next, the four-carbon homologation of the aldehyde 15 to E,E-dienamine 18 could be achieved efficiently under mild conditions by iodomethylenation with CrCl_2 -CHI_3, with subsequent Pd-catalyzed coupling to the vinylstannane 12 followed by mild cleavage of the FMOC group. Finally, the synthetic problem inherent to the construction of the chiral α, α-dimethyl-β-hydroxycarboxylic acid subunit was successfully solved. The diastereoselective aldol reaction of the conjugated Z-enal 23 with tin(II) enolate derived from chiral oxazolidinone 21 gave R,S-oxazinedione 24 as a single isomer, which was converted into the left half acid portion 33 via Pd-catalyzed coupling between 27 and 31. Final amide formation of 18 and 33 followed by deprotection gave the synthetic (1), which was identical with an authentic sample by NMR, IR, HPLC, and FAB mass spectrometric comparisons.
- 天然有機化合物討論会の論文
- 1991-09-07