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

Concise, flexible and high yielding approaches to the orsellinic acid type macrolides lasiodiplodin 1 and zeranol 3 are described which involve only metal-assisted or metal-catalyzed C-C-bond formations. Key steps are the efficient allylation of aryl triflates 14 and 25 either by Stille or by modified Suzuki coupling reactions, and the high yielding ring closure of the macrocyclic rings by RCM using the ruthenium carbene 18 as the catalyst. One of 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 insights into the structure/activity relationship of salicylihalamide. (C) 1999 Elsevier Science Ltd. All rights reserved.