CaltechAUTHORS
  A Caltech Library Service

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

Myers, Andrew G. and Tom, Norma J. and Fraley, Mark E. and Cohen, Scott B. and Madar, David J. (1997) A Convergent Synthetic Route to (+)-Dynemicin A and Analogs of Wide Structural Variability. Journal of the American Chemical Society, 119 (26). pp. 6072-6094. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20180801-095322066

[img] PDF (Experimental details of compounds prepared in this paper) - Supplemental Material
See Usage Policy.

1892Kb
[img] PDF (Experimental details of compounds prepared in this paper (2)) - Supplemental Material
See Usage Policy.

206Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20180801-095322066

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/ja9703741DOIArticle
Additional Information:© 1997 American Chemical Society. Received February 4, 1997. Publication Date (Web): July 2, 1997.
Issue or Number:26
Record Number:CaltechAUTHORS:20180801-095322066
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180801-095322066
Official Citation:A Convergent Synthetic Route to (+)-Dynemicin A and Analogs of Wide Structural Variability. Andrew G. Myers, Norma J. Tom, Mark E. Fraley, Scott B. Cohen, and David J. Madar. Journal of the American Chemical Society 1997 119 (26), 6072-6094. DOI: 10.1021/ja9703741
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:88432
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Aug 2018 18:23
Last Modified:03 Oct 2019 20:06

Repository Staff Only: item control page