A Convergent Synthetic Route to (+)-Dynemicin A and Analogs of Wide Structural Variability

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• 作者：Andrew G. Myers ; Norma J. Tom ; Mark E. Fraley ; Scott B. Cohen ; and David J. Madar
• 刊名：Journal of the American Chemical Society
• 出版年：1997
• 出版时间：July 2, 1997
• 年：1997
• 卷：119
• 期：26
• 页码：6072 - 6094
• 全文大小：1528K
• 年卷期：v.119,no.26(July 2, 1997)
• ISSN：1520-5126

文摘

An enantioselective synthetic route to (+)-dynemicin A(1) is described that involves as the key andfinalstep the Diels-Alder cycloaddition of the quinone imine 6with the isobenzofuran 107 followed by anoxidativeworkup to provide (+)-1 in 40% yield. The syntheticroute begins with the condensation of (-)-menthylacetoacetateand trans-ethyl crotonate to form the crystallinecyclohexanedione 14, which is then transformed to theenantiomericallypure quinone imine 6 in 23 steps with an average yield of85% and an overall yield of 2-3%. Key features ofthissequence include the coupling of the enol triflate 11 andthe arylboronic acid 10 (90%), the thermaldeprotection/internal amidation of the coupling product 18 (84%), the useof 2-chloropyridine as an economical alternative to2,6-di-tert-butylpyridine to promote the reaction of thequinolone 9 and triflic anhydride (85%), thehighlystereoselective addition of the (Z)-enediyne 31to the quinoline 61 (89%), intramolecular acetylideaddition withinthe acetylenic ketone 66 (94%), and oxidation of the phenol76 with iodosobenzene to afford the quinoneimineprecursor 77 in 89% yield. Both the quinone imine andisobenzofuran components of the final coupling reactioncan be varied, thus providing an ideal route for the preparation of awide variety of dynemicin analogs.