Macrocycles by ring-closing-metathesis, XI: Syntheses of (R)-(+)-lasiodiplodin, zeranol slid truncated salicylihalamides

Concise, flexible and high yielding approaches to the orsellinic acid type macrolides lasiodiplodin 1 and zeranol 3 are described which involve only m etal-assisted or metal-catalyzed C-C-bond formations. Key steps are the eff icient allylation of aryl triflates 14 and 25 either by Stille or by modifi ed Suzuki coupling reactions, and the high yielding ring closure of the mac rocyclic rings by RCM using the ruthenium carbene 18 as the catalyst. One o f the synthesis intermediates, i.e. cycloalkene 16, can also be regarded as a truncated analogue of the potent anti-tumor agent salicylihalamide A 7. From the in-vitro cytotoxicity data of 16 it is possible to deduce first in sights into the structure/activity relationship of salicylihalamide. (C) 19 99 Elsevier Science Ltd. All rights reserved.