A Convergent Synthetic Route to (+)-Dynemicin A and Analogs of Wide Structural Variability
Abstract
An enantioselective synthetic route to (+)-dynemicin A (1) is described that involves as the key and final step the Diels−Alder cycloaddition of the quinone imine 6 with the isobenzofuran 107 followed by an oxidative workup to provide (+)-1 in 40% yield. The synthetic route begins with the condensation of (−)-menthyl acetoacetate and trans-ethyl crotonate to form the crystalline cyclohexanedione 14, which is then transformed to the enantiomerically pure quinone imine 6 in 23 steps with an average yield of 85% and an overall yield of 2−3%. Key features of this sequence include the coupling of the enol triflate 11 and the arylboronic acid 10 (90%), the thermal deprotection/internal amidation of the coupling product 18 (84%), the use of 2-chloropyridine as an economical alternative to 2,6-di-tert-butylpyridine to promote the reaction of the quinolone 9 and triflic anhydride (85%), the highly stereoselective addition of the (Z)-enediyne 31 to the quinoline 61 (89%), intramolecular acetylide addition within the acetylenic ketone 66 (94%), and oxidation of the phenol 76 with iodosobenzene to afford the quinone imine precursor 77 in 89% yield. Both the quinone imine and isobenzofuran components of the final coupling reaction can be varied, thus providing an ideal route for the preparation of a wide variety of dynemicin analogs.
Additional Information
© 1997 American Chemical Society. Received February 4, 1997. Publication Date (Web): July 2, 1997.Attached Files
Supplemental Material - ja6072_si.pdf
Supplemental Material - ja6072a_si2.pdf
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Additional details
- Eprint ID
- 88432
- DOI
- 10.1021/ja9703741
- Resolver ID
- CaltechAUTHORS:20180801-095322066
- Created
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2018-08-01Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field