Irofulven

A formal synthesis of7-protoilludene has been described. The distribution of ptaquiloside has been studied in four Danish bracken populations in order to evaluate the transfer of this carcinogenic sesquiterpene from ferns to the soil. An approach to the synthesis of pteridanone, the aglycone of the glucoside pteridanoside, has been reported. Studies on the structure–activity relationship of illudin analogues possessing a spiro-cyclobutane ring have been carried out. Illudin S has been identified as the sole antiviral compound present in an extract of mature fruiting bodies ofOmphalotus illudens. A library of forty-nine illudinoids has been preparedvia a three-step synthesis and tested against three cancer cell lines. The reaction of the antitumour agent irofulven with zinc and acetic acid led to a series of compounds, which present a more reduced toxicity to human leukaemia than irofulven. Synthetic studies towards the framework construction of the fomannosane sesquiterpene illudosin have been reported.

Finally, an equally impressive example of enyne RCM in total synthesis is illustrated by the Movassaghi group’s preparation of (-)-acylfulvene (51, Scheme 10) and (-)-irofulven, two members of the cytotoxic illudin family. Preparation of the disiloxane52was readily achievedviaunion of an appropriate alkyne and aldehyde, followed by silylation. This substrate is designed with great care, as TST ring-closing enyne metathesis must be achieved in the presence of an additional ‘spectator’ trisubstituted alkene, and for this the phenyl substituent proved crucial as a protecting group. Thus, initiation of the cascade cyclisation at the mono-substituted alkene was followed by dienyne RCM, terminating on the 1,1-disubstituted alkene, which afforded the 7,6-bicycle53in an outstanding 79% yield; notably, the use of less bulky or non-conjugated blocking groups on the trisubstituted alkene led to competing metathesis side-reactions.