An asymmetric synthesis of the pentacyclic core of stemofoline

On treatment with acid, an open-chain 5-acylamino-3,8-diketo-ester, methyl (4R,5S,7S)-7-benzyloxy-4-[(S)-1-benzyloxyprop-2-yl]-5-methoxycarbonylamino-3,8-dioxododecanoate, cyclised via a stereoselective Mannich reaction to give an 8-azabicyclo[3.2.1]octanone. Hydrogenolysis of this with in situ acetal formation, reduction of the ester and a further cyclisation gave a lactam, (4R,5R,8S,9R,105,12S,135)-13-butyl-8-methyl-1-aza-6,14-dioxapentacyclo[8.3.0.0(4,13)0(5,9).1(5,12)]tetradecan-2-one, that corresponds to the pentacyclic core of stemofoline. (C) 2013 Elsevier Ltd. All rights reserved.