Diverse synthesis of the C ring fragment of bryostatins via Zn/Cu-promoted conjugate addition of α-hydroxy iodide with enone

A convergent approach to 1,5-hydroxy ketones, the general precursors for constructing the C ring of bryostatins, has been developed via a Zn/Cu-promoted conjugate addition of alpha-hydroxy iodides with enones. The reaction leads to direct formation of the C21-C22 bond and tolerates diverse functionalities at the C17-, C18- and C24-positions. The approach also enables a more concise synthesis of the known C ring intermediate (10 longest linear steps and 14 total steps), in contrast to its previous synthesis (17 longest linear steps and 22 total steps) in our total synthesis of bryostatin 8. (C) 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.