Total synthesis of (G)-herbertenediol
A. Srikrishna
*
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.
1. Introduction
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.
1
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.
2
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.
3
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.
4
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.
4
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).
5
The mastigo-
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.
2,6
The phenolic herbertanes
4–7
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.
doi:10.1016/j.tet.2006.01.021
Keywords: Herbertanes; Mastigophorenes; RCM reaction; Claisen
rearrangement; Vicinal quaternary carbon atoms.
*
Corresponding author. Tel: C91 80 22932215; fax: C91 80 23600529;
e-mail: ask@orgchem.iisc.ernet.in