Formal synthesis of nanaomycin D via a Hauser-Kraus annulation using a chiral enone-lactone

A formal total synthesis of nanaomycin D has been achieved. The strategy employed made use of a one-pot cyclisation-stereoselective reduction of a hydroxyketone to install the pyranonaphthalene moiety after execution of a Hauser-Kraus annulation using a chiral enone-lactone as the Michael acceptor to append the gamma-lactone ring. The chirality in the chiral enone-lactone was established using a Sharpless asymmetric dihydroxylation. The enone-lactone used herein represents an attractive chiral synthon for the construction of other gamma-lactone containing pyranonaphthoquinones such as griseusin A and crisamicin A. (C) 2014 Elsevier Ltd. All rights reserved.