Total synthesis of (G)-herbertenediol
and G. Satyanarayana
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Received 28 September 2005; revised 3 December 2005; accepted 5 January 2006
Available online 25 January 2006
Abstract—A formal total synthesis of the sesquiterpene (G)-herbertenediol and its dimers mastigophorenes A–D has been accomplished,
starting from vanillin via 2,3-dimethoxy-5-methylbenzaldehyde. A combination of Claisen rearrangement and ring-closing metathesis
reactions were employed for the generation of the two vicinal quaternary carbons on a cyclopentane ring.
q 2006 Elsevier Ltd. All rights reserved.
Liverworts, belonging to the Hepaticae family, are endowed
with a rich and wide variety of mono-, sesqui- and
diterpenoids and/or lipophilic aromatic compounds. An
important endogenous character of the Hepaticae family is
that most of the sesquiterpenoids isolated from liverworts
are enantiomeric to those isolated from the higher plants.
Several compounds obtained from liverworts show a wide
spectrum of biological properties such as muscle relaxing
activity, antimicrobial, antifungal, 5-lipoxygenase, cyclo-
oxygenase, cytotoxic, insect antifeedant, neurotropic
sprouting, piscicidal, cathepsin B and L, calmodulin
inhibitory and anti-HIV activities. Liverworts from the
genus Herbertus contain herbertane sesquiterpenoids,
which are considered as chemical markers of the genus.
The herbertane group is a small group of aromatic
sesquiterpenes, isomeric to cuparenes, containing a steri-
cally crowded 1-aryl-1,2,2-trimethylcyclopentane carbon
framework incorporating two vicinal quaternary carbon
atoms on a cyclopentane ring. The ﬁrst member of this class
of sesquiterpenes, herbertene 1, was isolated in 1981 by
Matsuo and co-workers from the ethyl acetate extract of the
liverwort Herberta adunca (Dicks) Gray.
In 1982, Matsuo
and co-workers reported the isolation of three phenolic
herbertanes, a-herbertenol 2, a-formylherbertenol 3 and
b-herbertenol 4 along with herbertene 1 and cuparene
sesquiterpenes from the same liverwort.
Asakawa and co-
workers in 1982 reported the isolation of herbertene 1 and
the phenolic herbertenes, a-herbertenol 2 and b-herbertenol
4 from H. aduncus, H. sakuraii and H. subdetatus. Isolation
of more herbertenoids, herbertenediol 5 and herbertenolide
6 was reported in 1983 by Matsuo and co-workers.
In 1988 and 1991 Asakawa and co-workers reported the
isolation of the dimeric herbertanes, mastigophorenes A–D
7–10, dimers of herbertenediol 5, from the liverwort
Mastigophora diclados (Mastigophoraceae).
phorenes A–D 7–10 are presumably formed by one electron
oxidative phenolic coupling of herbertenediol 5.Sub-
sequently, isolation of a few other phenolic herbertanes
have been reported.
The phenolic herbertanes
have been shown to possess
interesting biological properties such as growth inhibiting
Tetrahedron 62 (2006) 2892–2900
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
Keywords: Herbertanes; Mastigophorenes; RCM reaction; Claisen
rearrangement; Vicinal quaternary carbon atoms.
Corresponding author. Tel: C91 80 22932215; fax: C91 80 23600529;