Cyclopentanoid cyanohydrin glucosides and amides of Lindackeria dentata

Article abstract of DOI:10.1055/s-2004-832628

A mixture of cyanogenic glucosides epivolkenin and taraktophyllin, 1,4-dihydroxy-2-cyclopentenecarboxamide, and uridine were isolated from leaves of Lindackeria dentata (Flacourtiaceae). Another cyclopentanoid amide, (1R,4S,5R)-1,4,5-trihydroxy-2-cyclopentenecarboxamide, was synthesized in two steps from gynocardin, and shown to have the same relative configuration as a partially identified amide previously isolated from L. dentata bark.

Full text of DOI:10.1055/s-2004-832628

Cyclopentanoid Cyanohydrin
Glucosides and Amides of
Lindackeria dentata
Jerzy W. Jaroszewski1, Patrick Ekpe2, Matthias Witt3
Abstract
A mixture of cyanogenic glucosides epivolkenin and taraktophyl-
lin, 1,4-dihydroxy-2-cyclopentenecarboxamide, and uridine
were isolated from leaves of Lindackeria dentata ꢀFlacourtia-
ceae). Another cyclopentanoid amide, ꢀ1R,4S,5R)-1,4,5-trihy-
droxy-2-cyclopentenecarboxamide, was synthesized in two
steps from gynocardin, and shown to have the same relative con-
figuration as a partially identified amide previously isolated
from L. dentata bark.
Plants produce cyanohydrin glycosides ꢀcyanogenic glycosides)
belonging to three main classes according to the structure of
amino acid from which they are biosynthesized [1], [2]. One class
comprises derivatives of mandelonitrile and its hydroxylated
counterparts, biosynthetically derived from phenylalanine or
tyrosine; the structural diversity within this group has been ex-
plored largely by Nahrstedt et al. [1], [2]. The other class includes
derivatives of the aliphatic amino acids valine and isoleucine [1],
[2], and the third comprises the relatively rare derivatives of the
non-proteinogenic amino acid 2-cyclopentenylglycine [1], [2],
[3], [4]. Biosynthesis, toxicology and ecology of cyanogenic gly-
cosides and more recently genetic engineering of cyanogenic
plants have attracted considerable interest. In this communica-
tion, we describe cyclopentanoid cyanohydrin glucosides and cy-
clopentanoid amides of Lindackeria dentata ꢀOliv.) Gilg, a species
belonging to the family Flacourtiaceae, which is characterized by
a variety of natural products apparently derived from 2-cyclo-
pentenylglycine [4], [5], [6], [7], [8].
1001
dentata is in accord with the general cyclopentene hydroxylation
pattern observed in Flacourtiaceae [5], [6], [7], [8].
The isolation of amides from extracts of cyanogenic plants was
first reported by Jaroszewski et al. [10] and Nahrstedt and
Rockenbach [11]. From the large amount of the amide isolated,
Leaves of L. dentata were extracted and fractionated to yield epi- Nahrstedt and Rockenbach concluded that it is a genuine natural
volkenin ꢀ1) [5] and taraktophyllin ꢀ2) [5] in the ratio of 2:3, product and not an artificial product of the isolation procedure
[11]. On the other hand, in our earlier work on plants containing
cyclopentanoid cyanogenic glucosides, a number of amides
isolated appeared to be formed during processing of plant mate-
rial [3], [8], [10].
along with the amide 3 [8] and uridine ꢀ4) [9]. The compounds
1±4 were identified on the basis of literature data [5], [8], [9].
The presence of derivatives of cis-2-cyclopentene-1,4-diol in L.
Dedicated to Professor Adolf Nahrstedt on the occasion of his retirement as
Editor-in-Chief of Planta Medica
The amide 3 was isolated previously from Passiflora suberosa;
the compound was believed to be enantiomerically pure and
had a large positive specific rotation ꢀ[a]D: + 2758) [15], as ex-
pected for the amide formed from 1 [10]. By contrast, the amide
isolated in the present work has a considerably lower specific ro-
tation ꢀ[a]D: + 1208). Since L. dentata produces both 1 and 2, their
hydrolysis would indeed afford a mixture of 3 and its levorota-
tory enantiomer, leading to the diminished optical rotation.
1
Affiliation: Department of Medicinal Chemistry, The Danish University of
2
Pharmaceutical Sciences, Copenhagen, Denmark ´ Botany Department, Uni-
versity of Ghana, Legon, Ghana ´ 3 Bruker Daltonik GmbH, Bremen, Germany
Correspondence: Prof. Jerzy W. Jaroszewski
´ Department of Medicinal
Chemistry ´ The Danish University of Pharmaceutical Sciences ´ Universi-
tetsparken 2 ´ 2100 Copenhagen ´ Denmark ´ Fax: +45 3530 6040. ´ E-mail:
jj@dfuni.dk
History
Bark of L. dentata has been studied previously by Gibbons et al.,
resulting in isolation of an amide formulated as 5 [12]. Neither
the relative stereochemistry at C-1, nor the absolute configura-
tion of the molecule have been determined [12]. We have now
performed the transformation of the classical cyclopentanoid
Part 27 in the series ªNatural Cyclopentanoid Cyanohydrin Glycosidesº
Received: April 28, 2004 ´ Accepted: July 15, 2004
Bibliography: Planta Med 2004; 70: 1001±1003 ´ ꢁ Georg Thieme Verlag KG
Stuttgart ´ New York ´ DOI 10.1055/s-2004-832628 ´ ISSN 0032-0943

glucoside gynocardin ꢀ6) into the corresponding, stereochemi- HPLC column with 6 mL/min of 15% aqueous MeOH ꢀrefracto-
cally well-defined amide 8. Thus, treatment of 6 with ammonia metric detection) to give 102 mg ꢀ24%) of the amide 7. The latter
afforded a novel glucoside 7, which was converted to 8 by clea- amide ꢀ80 mg) was dissolved in 1 mL of water and 2 mL of Helix
vage of the glucosidic linkage with Helix pomatia enzyme pre- pomatia crude glucuronidase/sulfatase enzyme preparation ꢀSig-
paration [13], [14]. The 1H- and 13C-NMR spectroscopic proper- ma) and left for 24 h at 378C. The solution was freeze-dried, the
ties of thus obtained 8 were identical with those reported [12], residue taken up with MeOH, filtered, the filtrate was evaporat-
1
including H chemical shifts of the hydroxy groups observed in ed, and the residue subjected to repeated HPLC as above, using
ꢀCD3)2SO. This proves that the relative configuration of the amide 7.5% and then 1.2% aqueous MeOH; yield: 13 mg ꢀ33%) of 8
isolated by Gibbons et al. [12] is identical with that of 8 because ꢀ20 mg or 25% of 7 was also recovered).
epimers of hydroxylated cyclopentenes have distinctly different
NMR spectra [5], [10]. However, the synthetic amide 8 was, as ex- ꢀ1R,4S,5R)-1-b-D-Glucopyranosyloxy-4,5-dihydroxy-2-cyclopentene-
1
pected [10], strongly dextrorotatory ꢀ[a]D: + 838), whereas specif- 1-carboxamide ꢀ7): [a]2D5: + 698 ꢀc 0.93, MeOH); H-NMR ꢀCD3OD,
ic rotation of the L. dentata isolate had been reported to be ±108 600 MHz): d = 6.05 ꢀ1H, dd, J = 6.3 and 1.6 Hz, H-3), 5.88 ꢀ1H, dd,
in the same solvent [12]. This value of the specific rotation J = 6.3 and 1.4 Hz, H-2), 4.71 ꢀ1H, dt, J = 5.8 and approx. 1.5 Hz, H-
corresponds neither to pure 8 nor to its pure enantiomer. From 4), 4.56 ꢀ1H, d, J = 7.7 Hz, H-1¢), 4.32 ꢀ1H, d, J = 5.8 Hz, H-5), 3.85
the reported optical rotation [12], the amide isolated by Gibbons ꢀ1H, dd, J = 11.9 and 2.2 Hz, H-6¢B), 3.64 ꢀ1H, dd, J = 11.9 and 5.9
et al. thus appears to be a mixture of the optical antipodes that Hz, H-6¢A), 3.39±3.24 ꢀm, 4H, H-2¢, H-3¢, H-4¢ and H-5¢); 13C-NMR
could arise by hydrolysis of a mixture of 7 and its yet unknown ꢀCD3OD, 150 MHz): d = 175.2 ꢀCONH2), 140.3 ꢀC-3), 131.6 ꢀC-2),
isomer having all chiral centers in the aglucone portion inverted. 99.7 ꢀC-1¢), 94.0 ꢀC-1), 88.3 ꢀC-5), 80.1 ꢀC-4), 78.2 and 78.1 ꢀC-3¢
and C-5¢), 75.1 ꢀC-2¢), 71.6 ꢀC-4¢), 62.7 ꢀC-6¢); HRMS: m/z
The present work contributes to the knowledge of structural di- 344.09492 ꢀM + Na+), C12H19NO9Na+ requires 344.09520.
versity of cyclopentanoid natural products in the family Flacour-
=
tiaceae. In particular, the presence of amides as apparent pro- ꢀ1R,4S,5R)-1,4,5-Trihydroxy-2-cyclopentene-1-carboxamide ꢀ8):
1
ducts of metabolism of cyanohydrin glucosides is of interest. [a]D25: + 838 ꢀc 0.3, MeOH), lit. [12]: ±108 ꢀc 0.1, MeOH); H-NMR
The described conversion of 6 to 8 is a prototype experiment en- ꢀCD3OD, 400 MHz): d = 5.95 ꢀ1H, dd, J = 6.3 and 1.5 Hz, H-3),
abling access to various non-glucosidic hydroxylated cyclopen- 5.65 ꢀ1H, dd, J = 6.3 and 1.5 Hz, H-2), 4.65 ꢀ1H, dt, J = 5.8, 1.5
tane derivatives.
and 1.5 Hz, H-4), 3.96 ꢀ1H, d, J = 5.8 Hz, H-5) ꢀthe assignment of
H-2 and H-3 was confirmed by a NOESY spectrum); 13C-NMR
ꢀCD3OD, 100 MHz): d = 177.0 ꢀCONH2), 138.3 ꢀC-2), 133.9 ꢀC-3),
91.6 ꢀC-5), 87.7 ꢀC-1), 80.3 ꢀC-4); 1H- and 13C-NMR spectra in
ꢀCD3)2SO as reported [12]; HRMS: m/z = 182.04221 ꢀM + Na+),
Materials and Methods
Leaves of L. dentata ꢀOliv.) Gilg were collected in Atowa Range C6H9NO4Na+ requires 182.04238.
Forest Reserve, Ghana; a voucher specimen ꢀGC47689) was de-
1002
posited in Herbarium GC ꢀGhana Herbarium, Botany Depart-
ment, University of Ghana, Legon). Dried and milled plant mate- Acknowledgements
rial ꢀ130 g) was divided in three portions, and each portion added
slowly to l L of boiling 80% aqueous MeOH. The mixtures were Ms. Tanja Thorslund Andersen is thanked for technical assistance.
boiled for 5 min, chilled on ice, filtered, and evaporated. A total
of 21.5 g of crude extract was obtained, which was coated on
75 g of silica gel ꢀMatrex Silica gel 60A, 37±70 mm) using 80% References
MeOH, and chromatographed on an 18”10 cm I. D. silica gel col-
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Letter¼ Planta Med 2004; 70: 1001±1003