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An Asymmetric Formal Synthesis of Fasicularin
Author(s) -
Fenster Michaël D. B.,
Dake Gregory R.
Publication year - 2005
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200400749
Subject(s) - trifluoromethanesulfonate , enol , natural product , chemistry , epoxide , stereochemistry , formal synthesis , thiocyanate , combinatorial chemistry , ring (chemistry) , organic chemistry , catalysis
An asymmetric formal synthesis of fasicularin ( 1 ) is described. This natural product, isolated from the extracts of the marine invertebrate Nephteis fasicularis , has shown modest cytotoxicity towards Vero cells. Fasicularin is among only two members of the cylindricine family of natural products, along with lepadiformine ( 2 ), to possess a trans A–B ring junction. Key steps of this approach to 1 involve a siloxy‐epoxide semipinacol rearrangement of 5 to 6 , a B‐alkyl Suzuki–Miyaura coupling reaction by using enol trifluoromethanesulfonate 19 and a substrate‐directed hydrogenation reaction of 24 . This formal synthesis also highlights the difficulty in the incorporation of the thiocyanate functionality present in 1 .