Notes
8-epi-Muralioside, an Iridoid Glucoside from Linaria arcusangeli
†
Armandodoriano Bianco, Marcella Guiso,* and Mariaceleste Martino
Dipartimento di Chimica Universita ` “La Sapienza” and CNR, Centro di Studio per la Chimica delle Sostanze Organiche
Naturali, Piazzale A. Moro 5, I 00185, Roma, Italy
Marcello Nicoletti, Mauro Serafini, and Lamberto Tomassini
Dipartimento di Biologia Vegetale, Universita ` “La Sapienza”, Piazzale A. Moro 5, I 00185, Roma, Italy
Received August 2, 1996
X
A new polyhydroxylated iridoid glucoside, 1, was isolated from Linaria arcusangeli. The
structure of 1 could arise from a regioselective acid-catalyzed-like opening of the epoxide ring
of antirrhinoside, the main iridoid constituent of the plant. Compound 1 is the 8-epimer of
muralioside, previously isolated from Cymbalaria muralis.
In a program aimed toward the phytochemical inves-
tigation of endemic Sardinian species, we have exam-
ined Linaria arcusangeli Atzei et Camarda,
1
an inter-
esting case of endemism located only in a restricted area
about 40 km northeast of Cagliari. The plant is rich in
iridoids,
2
including antirrhinoside and antirrhide, which
are chemotaxonomic markers of the Scrophularioideae-
Antirrhineae tribe of the family of Scrophulariaceae, to
which the genus Linaria belongs.
3,4
An examination of
the most polar glycosidic constituents resulted in the
isolation of macfadienoside and a new iridoid gluco-
side, 1.
From an examination of its
1
H-NMR spectrum, com-
pound 1 was assigned as a polyhydroxylated iridoid
glucoside. Hydroxyl groups could be located at several
positions, namely, C-5 owing to the signal observed for
H-4 (5.70 ppm), which appeared as a doublet of doublets
(J
3,4
) 6.5 Hz and J
4,9
) 0.5 Hz); C-6 and C-7 because
of the signals of two doublets at 4.68 and 4.10 ppm (J
6,7
) 4.2 Hz); and C-8 from the singlet occurring at 1.68
ppm, assigned to H
3
-10. To confirm the hydroxyl
pattern, reaction of 1 with Ac
2
O/pyridine under mild
conditions gave the hexaacetyl derivative, 2, whose
NMR analysis demonstrated the presence of two sec-
ondary esterified hydroxyl groups at C-6 and C-7 and
two free tertiary hydroxyl groups at C-5 and C-8.
Concerning the stereochemistry of the hydroxyls
present in the aglucone part of 1, the value of J
6,7
(4.2
Hz) is indicative of a cis relative configuration between
H-6 and H-7, since in the trans configuration the
coupling constant value would lie in a range between
9.0 and 9.7 Hz. A configuration could be assigned to
OH-5 by analogy with that of other known iridoid
glycosides, in contrast to the recent isolation of a C-5,
C-9 trans iridoid.
5
In any case, the configurations at
C-5, C-6, and C-9 in 1 could be confirmed by the
presence of an evident NOE effect between H-4 and H-6.
Other stereogenic centers were assigned for 1 on the
basis of NOE experiments: H-9 and H
3
-10 exhibited a
strong NOE effect, as did H-6 and H-7. Owing to these
observations and the absence of a NOE effect between
H
3
-10 and H-7, a configuration could be assigned to
OH-6, OH-7, and H
3
-10. Furthermore, the chemical
shift value of the last group appears to be very different
from that observed at 1.34 ppm in muralioside, an
iridoid glucoside epimeric to 1 at C-8, recently isolated
from Cymbalaria muralis.
6
Similar data for H
3
-10 have
been reported for other polyhydroxylated iridoids with
the same configuration of muralioside at C-8, as exem-
plified by physoside (1.27 ppm)
7
and lamiide (1.08
ppm).
8
A deshielded value for the configuration of
H
3
-10 versus an R configuration is in accordance with
previous data (e.g., in the pair plantarenaloside/stan-
sioside).
9
Interestingly, in the
13
C-NMR spectrum of 1
the differences for the C-10 signal among these iridoids
are not so evident. Therefore, on the basis of the
interpretation of the above-reported data, the structure
of 8-epi-muralioside can be assigned to 1.
Although C-8 iridoid epimers are known when sub-
stituted with CH
3
/H or with CH
2
OH/OH,
10
and several
iridoids exhibit an R-CH
3
/-OH C-8 substitution,
11
to our
knowledge compound 1 is the second case of glycosidic
iridoid having -CH
3
/R-OH C-8 substitution.
12
From a biogenetic point of view, the structure 1 could
arise from a regioselective acid catalyzed-like opening
of the epoxide ring of antirrhinoside, the main iridoid
constituent of the plant.
* To whom correspondence should be addressed. Fax: 39 6 490631.
E-mail: adbianco@axrma.uniroma1.it.
†
Iridoids in the flora of Italy. 16. Part 15: Reference 6.
X
Abstract published in Advance ACS Abstracts, February 1, 1997.
366 J. Nat. Prod. 1997, 60, 366-367
S0163-3864(96)00573-3 CCC: $14.00 © 1997 American Chemical Society and American Society of Pharmacognogy