The novel flavan-3-ol, (2R,3S)-guibourtinidol and its diastereomers

Article abstract of DOI:10.1016/S0031-9422(99)00348-9

The novel (2R,3S)-guibourtinidol, representing the first flavan-3-ol with 4',7-dihydroxy phenolic substitution pattern, was identified in the heartwood of Cassia abbreviata. Asymmetric dihydroxylation of (E)-1-(4'-O- methoxymethylphenyl)-3-(2',4'-di-O-met

Full text of DOI:10.1016/S0031-9422(99)00348-9

Phytochemistry 52 (1999) 1153±1158
The novel ¯avan-3-ol, (2R,3S )-guibourtinidol and its
diastereomersp
Reinier J.J. Nela, Makhosazana Mthembua, Johan Coetzeea, Hendrik van Rensburga,
Elfranco Malana,Ã, Daneel Ferreirab,*
aDepartment of Chemistry, University of the Orange Free State, P.O. Box 339, Bloemfontein, 9300 South Africa
bNational Center for the Development of Natural Products, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of
Mississippi, Mississippi, MS 38677, USA
Received 22 March 1999; received in revised form 18 May 1999
Abstract
The novel (2R,3S)-guibourtinidol, representing the ®rst ¯avan-3-ol with 4',7-dihydroxy phenolic substitution pattern, was
identi®ed in the heartwood of Cassia abbreviata. Asymmetric dihydroxylation of (E)-1-(4'-O-methoxymethylphenyl)-3-(20,40-di-
O-methoxymethylphenyl)-propene with AD-mix-a or AD-mix-b and subsequent acid-catalyzed cyclization a€orded the four free
phenolic guibourtinidol diastereomers, essentially enantiopure and in good yield. # 1999 Elsevier Science Ltd. All rights
reserved.
Keywords: Cassia abbreviata; Flavanoids; Phenolics; Asymmetric dihydroxylation
1. Introduction
1982) and Colophospermum mopane (Malan et al.,
1990).
Continuation of the work on Cassia abbreviata
(Malan et al., 1996) revealed the presence of the novel
(2R,3S )-4',7-dihydroxy¯avan-3-ol, guibourtinidol 1,
representing the ®rst entry into the guibourtinidol
series of diastereomeric ¯avan-3-ols. The structure of
compound 1 and stereoselective synthesis of the free
phenolic diastereomers 1 and 4±6 are described here.
Pro- and leucoguibourtinidins with their 4',7-dihy-
droxy phenolic functionality represent a relatively rare
group of proanthocyanidins which, while occurring as
minor components in Australian Acacia species
(Tindale & Roux, 1974), predominate in the Southern
African species, Guibourtia coleosperma (Roux & De
Bruyn, 1963; Saayman & Roux, 1965; Steynberg,
Ferreira & Roux, 1983, 1987), Julbernardia globi¯ora
(Pelter, Amenechi, Warren & Harper, 1969), Acacia
luederitzii (Du Preez, Rowan & Roux, 1970; Ferreira,
Du Preez, Wijnmaalen & Roux, 1985) and Cassia
abbreviata (Malan, Swinny, Ferreira & Steynberg,
1996). A limited number of guibourtinidol derivatives
were also found in Cassia ®stula (Patil & Deshpande,
2. Results and discussion
Guibourtinidol 1 was initially puri®ed and identi®ed
1
as the 4',7-di-O-methyl-3-O-acetyl derivative 2. The H
NMR spectrum (Table 1) showed an ABMX spin sys-
tem in the heterocyclic region and ABX and AA'BB'
spin patterns for two aromatic rings. When taken in
conjunction with the presence of an O-acetyl (d 1.98)
and two O-methyl (d 3.82, 3.80) resonances, these fea-
tures were reminiscent of the protons of 4',7-di-O-
methyl-3-O-acetyl¯avan-3-ol (Van Rensburg, Van
Heerden & Ferreira, 1997b). The aromatic spin sys-
p Part 6 in the series `Stereoselective synthesis of ¯avonoids'. Part 5
(Nel, Van Heerden, Van Rensburg & Ferreira, 1998).
* Corresponding authors. Tel.: +1-91-601-232-1572; fax: +1-91-
601-232-7062.
E-mail address: dferreir@olemiss.edu (D. Ferreira).
0031-9422/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved.
PII: S0031-9422(99)00348-9

1154
R.J.J. Nel et al. / Phytochemistry 52 (1999) 1153±1158
Table 1
1H (300 MHz) and 13C (75.46 MHz) NMR data for guibourtinidols 1, 4±6 and derivative 2 at 296 K. Splitting patterns and J-values (Hz) are
given in parentheses
Position
2
1H(CDCl3)
1/6 1H[(CD3)2CO]
4/5 1H[(CD3)2CO]
2
13C(CDCl3)
1/6 13C[(CD3)2CO]
4/5 13C[(CD3)2CO]
2
5.12 (d, 6.5)
5.30 (m)
4.66 (d, 8.0)
4.02 (m)
4.98 (d, 1.5)
4.20 (m)
78.6
69.8
28.7
28.7
82.4
67.7
79.1
66.4
33.2
3
4eq
4ax
5
2.99 (dd, 5.0, 16.0)
2.82 (dd, 7.0, 16.0)
6.95 (d, 9.0)
2.93 (dd, 5.0, 16.0)
2.74 (dd, 9.0, 16.0)
6.88 (d, 9.0)
3.09 (dd, 4.0, 16.0)
2.73 (dd, 3.5, 16.0)
6.87 (d, 8.0)
33.3
33.3
130.5
108.4
130.5
108.6
157.2
102.8
155.6
111.9
130.7
129.0
115.2
157.6
130.9
108.6
157.0
103.0
155.8
111.0
130.6
128.6
114.9
157.2
6
6.53 (dd, 2.5, 9.0)
6.39 (dd, 2.5, 9.0)
6.37 (dd, 2.5, 8.0)
7
159.9
101.6
8
6.54 (d, 2.5)
6.30 (d, 2.5)
6.33 (d, 2.5)
9
10
154.8
111.4
1'
130.5
128.0
2'/6'
3'/5'
4'
7.30 (d, 9.0)
6.90 (d, 9.0)
7.24 (d, 9.0)
6.83 (d, 9.0)
7.33 (d, 9.0)
6.82 (d, 9.0)
114.3
159.9
OMe
OAc
3.82, 3.80 (each s)
1.98 (s)
55.7, 55.6
21.4, 170.6
tems were di€erentiated via the appropriate correlation
experiments using the H-2(C) and H-4eq (C) resonances
as reference signals. The 2,3-trans relative con®gur-
ation was evident from the J2,3-value of 6.5 Hz, such
a small coupling constant presumably re¯ecting signi®-
cant contributions of A-conformers to the ensemble of
Ferreira, 1997a; Van Rensburg et al., 1997b) to the
®rst synthesis of free phenolic ¯avan-3-ols. Owing to
the acid lability of methoxymethyl derivative, the
MOM functionality was used as a protecting group.
The (E )-retro-2,4,4'-tri-O-methoxymethylchalcone 7
(Scheme 1) was prepared in 72% yield by base-cata-
lyzed condensation of 2,4-di-O-methoxymethylbenzal-
3
conformers related to the C-ring (Tobiason
&
Hemingway, 1994). A high amplitude negative Cotton
e€ect ( 3864) at 283.9 nm in the CD spectrum of de-
rivative 2 was in accordance with chiroptical data of
¯avan-3-ol derivatives with (2R,3S ) absolute con®gur-
ation (Korver & Wilkins, 1971; Van Rensburg et al.,
1997b). The FAB mass spectrum showed a molecular
ion at m/z 327 [M-H]+, thus con®rming the C19H20O5
molecular formula for compound 2.
dehyde
and
4-O-methoxymethylacetophenone.
Hydrogenation of chalcone 7 in the presence of 5%
Pd/C a€orded the retro-dihydrochalcone 8 in quanti-
tative yield. Subsequent reduction with NaBH4 gave
the 1,3-diarylpropan-1-ol 9 (99%) which was converted
into the (E )-1,3-diarylpropene 10 (69%) using SOCl2
and 1,8-diazabicyclo[5.4.0]undec-7-ene (1,8-DBU).
Treatment of the (E )-1,3-diarylpropene 10 with AD-
mix-a in the two-phase system tBuOH:H2O (1:1)
(Jeong, Sjo & Sharpless, 1992; Kolb, Van Nieuwenhze
& Sharpless, 1994; Sharpless et al., 1992; Wang, Zhang
& Sharpless, 1993) a€orded the (1S,2S )-syn-diol 11a
(3J1,2=6.3 Hz) in high yield (79%) and optical purity
(99% ee). The (1R,2R )-syn-diol 11b (78% yield, 99%
ee) was similarly obtained by using AD-mix-b in the
same two-phase system. The enantiomeric purity of
Guibourtinidol 1 was also puri®ed as the peracetate
3 which a€orded the free phenolic form via alkaline
hydrolysis under an N2 atmosphere, i.e. conditions
which do not e€ect epimerization at C-2 of the ther-
modynamically more stable 2,3-trans-¯avan-3-ol
1
(Kennedy, Munro, Powell, Porter & Foo, 1984).
Assignment of the 13C NMR spectra (Table 1) of de-
rivative 2 and of the free phenols, (2R,3S )-guibourtini-
dol 1, (2S,3R )-guibourtinidol 6 (ent-guibourtinidol),
1
the diols was determined by H NMR using Eu(tfc)3
(2R,3R )-guibourtinidol
(2S,3S )-guibourtinidol 5 (ent-epiguibourtinidol) were
based on HMBC and HMQC experiments.
4
(epiguibourtinidol) and
as a chiral shift reagent while the absolute con®gur-
ation was assigned according to the Sharpless model
(Jeong et al., 1992; Sharpless et al., 1992; Van
Rensburg et al., 1997b).
The identi®cation of guibourtinidol 1 as the ®rst
naturally occurring ¯avan-3-ol with 4',7-dihydroxy
phenolic substitution presented the opportunity to syn-
thesize the four diastereomers 1 and 4±6 by adapting
our recently developed protocol towards ¯avan-3-ol
derivatives via asymmetric dihydroxylation of 1,3-dia-
rylpropenes and subsequent acid-catalyzed cyclization
Simultaneous deprotection and cyclization of the
(1S,2S )-syn-diol 11a with 3M HCl in methanol at
608C gave (2R,3S )-2,3-trans-4',7-dihydroxy¯avan-3-ol
1
(guibourtinidol, 60% yield, 99% ee) and the
(2S,3S )-2,3-cis-4',7-dihydroxy¯avan-3-ol 5 (ent-epigui-
bourtinidol, 18% yield, 99% ee). The (1R,2R )-syn-diol
11b similarly a€orded the (2S,3R )- and (2R,3R )-4',7-
(Van Rensburg, Van Heerden, Bezuidenhoudt
&

R.J.J. Nel et al. / Phytochemistry 52 (1999) 1153±1158
1155
Scheme 1. Reagents and conditions: (i) H2/5% Pd±C; (ii) NaBH4 in EtOH; (iii) SOCl2 in CH2Cl2, then DBU; (iv) AD-mix-a or AD-mix-b, t-
BuOH:H2O (1:1), MeSO2NH2, 08C; (v) 3M HCl, MeOH-H2O (3:1), re¯ux.
dihydroxy¯avan-3-ols 6 (ent-guibourtinidol, 61%, 99%
ee) and 4 (epiguibourtinidol, 20%, 99% ee), respect-
ively. The optical purity of the ¯avan-3-ols was
1
assessed by H NMR using Eu(tfc)3 as a chiral shift re-
agent for the per-O-acetates, which consistently indi-
cated the presence of a single enantiomer. Comparison
of the CD data (see Experimental) of the synthetic 2,3-
3
3
trans-(1/6; J2,3=8.0 Hz) and 2,3-cis-(4/5; J2,3=1.5
Hz) with published data (Korver et al., 1971; Van
Rensburg et al., 1997b), con®rmed the absolute stereo-
chemistry of the ¯avan-3-ols and also the con®guration
at C-2 of the syn-diols 11a/b as was derived from the
Sharpless model (Jeong et al., 1992; Sharpless et al.,
3. Experimental
1
1992; Van Rensburg et al., 1997a, 1997b). H and 13C
1H NMR spectra were recorded on a Bruker AM-
300 spectrometer for solutions as indicated, with TMS
as internal standard. FAB mass spectra were recorded
on a VG 70-70E instrument with a VG 11-250J data
system and an iontech saddle®eld FAB gun. TLC was
performed on precoated Merck plastic sheets (silica gel
PF254, 0.25 mm) and the plates were sprayed with
H2SO4-HCHO (40:1, v/v) after development.
Preparative plates (PLC) [20 Â 20 cm, Kieselgel PF254
(1.0 mm)] were air dried and used without prior acti-
vation. Column chromatography was performed on
Sephadex LH-20 in various columns, solvent systems
and ¯ow rates (to be speci®ed in each instance). Flash
column chromatography (FLC) was on Merck
Kieselgel 60 (230±400 mesh) under a positive pressure
NMR data of the ¯avan-3-ols 1 and 4±6 are collated
in Table 1.
We have thus demonstrated that the synthetic proto-
col to ¯avan-3-ol derivatives (Van Rensburg et al.,
1997a, 1997b), i.e. asymmetric dihydroxylation of 1,3-
diarylpropenes and subsequent acid-catalyzed cycliza-
tion of intermediate syn-diols, may be eciently
adapted to access for the ®rst time free phenolic ana-
logues of both 2,3-trans- and 2,3-cis-con®guration in
acceptable yields and in
a highly stereoselective
fashion. This method is currently being applied to
include the full range of naturally occurring ¯avan-3-
ols and of radio labelled analogues for much needed
biosynthetic studies.

1156
R.J.J. Nel et al. / Phytochemistry 52 (1999) 1153±1158
by means of compressed N2. Methylations were per-
formed with an excess of diazomethane in MeOH-
Et2O over a period of 48 h at 158C, while acety-
lations were conducted in Ac2O-pyridine at ambient
temperature. Evaporations were done under reduced
pressure at ambient temperature in a rotary evapor-
ator, and freeze-drying of aqueous solutions on a
Virtis 12 SL freezemobile.
(239), 551 (230), +21.7 (227), +503 (217) (found:
M+, 328.1279. C19H20O5 requires M+, 328.1273).
3.1.2. Guibourtinidol 1
Tan amorphous solid, 1H and 13C NMR spectral
data (Table 1), CD Ð see below (Found: M+,
258.0881. C15H14O4 requires M+, 258.0893).
3.2. Stereoselective Synthesis of Guibourtinidols 1 and
4±6
3.1. Isolation of phenolic compounds.
Heartwood drillings (2.7 kg) were repeatedly
extracted with Me2CO (3 Â 2.5 L) for 24 h periods at
room temperature (258C). The extract was concen-
trated by evaporation under vacuum at 358C. The con-
centrate was dissolved in H2O and then freeze-dried to
give a pale-brown powder (340.0 g). Two portions (25
g) of the Me2CO extract were separated on Sephadex
LH-20/EtOH columns (5 Â 160 cm) with ¯ow rate of 1
ml/min, 32 min fractions. The fractions from columns
A and B were combined as follows: C1 (tubes 17±28,
594.9 mg), C2 (29±40, 126 mg), C3 (48±57, 232 mg), C4
(69±77, 144 mg), C5 (78±86, 132 mg), C6 (91±103, 400
mg), C7 (109±133, 2.72 g), C8 (134±144, 1.34 g), C9
(145±154, 3.67 g), C10 (155±189, 7.34 g), C11 (190±207,
1.69 g), C12 (208±237, 3.34 g), C13 (238±288, 2.33 g),
C14 (289±341, 2.75 g), C15 (342±376, 508 mg), C16
(377±404, 432 mg), C17 (405±442, 615 mg), C18 (443±
471, 235 mg), C19 (472±940, 614 mg) and C20 (942±
1500, 802 mg). Only fraction C6 will be dealt with
here.
3.2.1. 4,4'-Tri-O-methoxymethyl-retro-chalcone 7
To a solution of 4-O-methoxymethylacetophenone
(3 mmol) was added 50% aq. KOH (0.4 ml/mmol acet-
ophenone) and the mixture was stirred at rt for 30
min. 2,4-Di-O-methoxymethylbenzaldehyde (3.6 mmol)
was added and the mixture was stirred at rt until dis-
appearance of the acetophenone. Water (50 ml) was
added and the mixture was extracted with Et2O
(4 Â 20 ml). Drying of the extracts with Na2SO4 fol-
lowed by evaporation and FLC in hexane-benzene-
Me2CO (5:4:1) a€orded the title compound 7 (Rf 0.34
in hexane-benzene-Me2CO, 5:4:1) as light-yellow nee-
dles from EtOH (72% yield), m.p. 46±478C; dH
(CDCl3) 8.13 (d, J 15.8. H-b), 8.04 (d, J 9.1, H-2',6'),
7.62 (d, J 9.0, H-6), 7.55 (d, J 15.8, H-a), 7.13 (d, J
9.1, H-3',5'), 6.87 (d, J 2.4, H-3), 6.76 (dd, J 9.0 and
2.4, H-5), 5.29, 5.27, 5.22 (3 Â s, OCH2OCH3), 3.53,
3.52, 3.51 (3 Â s, OCH2OCH3) (Found: M+, 388.1517.
C21H24O7 requires M+, 388.1522).
Methylation of a PLC puri®ed portion (200 mg) [Rf
0.64, benzene-Me2CO-MeOH (6:3:1)] of fraction C6
followed by PLC separation in benzene-Me2CO (9:1,
Â1) a€orded four bands [Rf 0.91 (4.7 mg), 0.71 (7
mg), 0.54 (10.4 mg), 0.42 (13 mg)] of which only the
latter band was acetylated. Puri®cation by PLC in ben-
zene yielded the permethylaryl ether acetate 2, Rf 0.22
(12.3 mg). The remaining bands still comprised mix-
tures and were not further investigated.
The remaining portion of fraction C6 (200 mg) was
acetylated and puri®ed by PLC in benzene-Me2CO
(96:4, Â2) to a€ord a main band at Rf 0.54 (5.8 mg)
which gave the full acetate 3 of guibourtinidol 1. The
acetylated compound was hydrolyzed in 1% KOH and
MeOH for 5 min under N2 at re¯ux temp. to give the
free phenolic compound 1, Rf 0.46 (5.7 mg).
3.2.2. 2,4,4'-Tri-O-methoxymethyl-retro-
dihydrochalcone 8
A solution of the retro-chalcone 7 (16 mmol) in
EtOH (200 ml) was hydrogenated over 5% Pd±C (1
mg/10 mg chalcone) until all the chalcone was con-
sumed (TLC). The catalyst was ®ltered o€ and the
EtOH evaporated to a€ord the title compound 8 (Rf
0.47 in hexane-benzene-Me2CO, 5:4:1) as a colourless
oil in quantitative yield: dH 7.97 (d, J 9.1, H-2',6'),
7.12 (d, J 8.3, H-6), 7.08 (d, J 9.1, H-3',5'), 6.81 (d, J
2.4, H-3), 6.66 (dd, J 8.3 and 2.4, H-5), 5.25, 5.21, 5.16
(3 Â s, OCH2OCH3), 3.50, 3.49 (Â2) (2 Â s,
OCH2OCH3), 3.22 (m, b±CH2), 3.01 (m, a-CH2)
(Found: M+, 390.1671. C21H26O7 requires M+,
390.1679).
The low yields of the permethylaryl ether acetate 2
and the full acetate 3 may be ascribed to the extremely
complex phenolic mixture which permits the isolation
of only those compounds which are visible as discrete
bands on PLC.
3.2.3. 1-(4'-O-Methoxymethylphenyl)-3-(20,40-di-O-
methoxymethylphenyl)-1-propanol 9
To a solution of the retro-dihydrochalcone 8 (15
mmol) in EtOH (200 ml) was added NaBH4 (60 mmol,
4 equiv.) and the mixture was stirred at rt for 12 h. It
was diluted with H2O (100 ml), extracted with Et2O
(3 Â 100 ml), the combined extracts dried (Na2SO4)
and the solvent evaporated to give the title alcohol 9
as a colourless oil in quantitative yield (Rf 0.21 in hex-
3.1.1. 4',7-Di-O-methyl-3-O-acetyl guibourtinidol 2
Yellowish brown amorphous solid, dH and dC NMR
(Table 1); CD: D emax [l (nm)] 3864 (284), +5481

R.J.J. Nel et al. / Phytochemistry 52 (1999) 1153±1158
1157
ane-benzene-Me2CO, 5:4:1); dH 7.30 (d, J 8.8, H-2',6'),
7.06 (d, J 8.2, H-60), 7.03 (d, J 8.8, H-3',5'), 6.80 (d, J
2.3, H-30), 6.66 (dd, J 8.2 and 2.3, H-50), 5.19 (Â2),
5.16 (3 Â s, OCH2OCH3), 4.63 (m, H-1), 3.50 (Â2),
3.48 (3 Â s, OCH2OCH3), 2.69 (m, 3-CH2), 2.03 (m, 2-
CH2) (Found: M+, 392.1841. C21H28O7 requires M+,
392.1836).
13.8 and 4.2) and 2.64 (dd, J 13.8 and 8.9) (3-CH2),
2.57 (d, J 4.3, 2-OH); CD: D emax [l (nm)] 230 (271),
+4200 (232) (Found: M+, 408.1791. C21H28O8
requires M+, 408.1784).
3.2.6. (1R,2R)-syn-1-(4'-O-Methoxymethylphenyl )-3-
(20,40-di-O-methoxymethyl-phenyl )-propane-1,2-diol
11b
3.2.4. (E)-1-(4'-O-Methoxymethylphenyl)Ð3-(20,40-di-
O-methoxymethylphenyl)-propene 10
CD: Demax [l (nm)] +210 (272), 4300 (233); The
1H NMR spectral data corresponded to those indi-
cated for 11a (Found: M+, 408.1789. C21H28O8
requires M+, 408.1784.
Freshly distilled SOCl2 (24 mmol, 2 equiv.) was
added dropwise to a solution of the alcohol 9 (12
mmol) in dry CH2Cl2 (15 ml), the mixture was stirred
at rt for 5 min, dry benzene (20 ml) was added and the
mixture evaporated to dryness at 508C. The resulting
chloropropane was dissolved in dry benzene (15 ml),
1,8-DBU (24 mmol, 2 equiv.) was added and the sol-
ution was re¯uxed for 12 h. Satd. aq. NH4Cl was
added and the mixture was extracted with Et2O
(3 Â 50 ml), the combined extract washed with water
(50 ml), dried (Na2SO4) and evaporated to dryness.
The mixture was puri®ed by PLC in hexane-benzene-
Me2CO (5:4:1) to give propene 10 as a clear oil (Rf
0.62, 69%); dH 7.28 (d, J 8.9, H-2',6'), 7.10 (d, J 8.3,
H-60), 6.97 (d, J 8.9, H-3',5'), 6.82 (d, J 2.4, H-30),
6.68 (dd, J 8.3 and 2.4, H-50), 6.37 (d, J 15.7, H-1),
6.23 (dt, J 15.7 and 6.6, H-2), 5.21, 5.18, 5.17 (3 Â s,
OCH2OCH3), 3.50, 3.49 (Â2), (3 Â s, OCH3OCH3),
3.3. General procedure for preparation of the ¯avan-3-
ols
A solution of the diol 11a/11b (100 mg, 0.25 mmol)
and 3 M HCl (0.4 ml) in H2O:MeOH [1:3 (0.6 ml)]
was stirred at 608C for 5 h and then diluted with ice
water (10 ml). The aq. solution was extracted with
Et2O (4 Â 20 ml), dried (Na2SO4) and the solvent
evaporated. Puri®cation by PLC in CHCl3-MeOH
(9:1) a€orded the 2,3-trans-¯avan-3-ols 1 (Rf 0.38,
60%) and 6 (61%) as well as the 2,3-cis-analogues 4
(Rf 0.33, 20%) and 5 (18%).
3.3.1. (2R,3S)-4',7-Dihydroxy¯avan-3-ol 1
dH and dC (Table 1); CD: Demax [l (nm)]= 1800
(275), +3000 (239) (Found: M+, 258.0889. C15H14O4
requires M+, 258.0893).
3.48 (d,
J
6.6, 3-CH2) (Found: M+, 374.1722.
C21H26O6 requires M+, 374.1730).
3.3.2. (2S,3R)-4',7-Dihydroxy¯avan-3-ol 6
CD: Demax [l (nm)] +1700 (274), 3000 (239). The
1H and 13C NMR spectral data corresponded to those
indicated for 1 (Found: M+, 258.0883. C15H14O4
requires M+, 258.0893).
3.2.5. (1S,2S)-syn-1-(4'-O-Methoxymethylphenyl )-3-
(20,40-di-O-methoxymethyl-phenyl )-propane-1,2-diol
11a
A 10 ml round-bottomed ¯ask, equipped with a
magnetic stirrer was charged with tBuOH (2.5 ml),
water (2.5 ml) and AD-mix-a or -b (700 mg). Stirring
of the mixture at rt produced two clear phases; the
lower aq. phase appearing bright yellow. MeSO2NH2
(47.6 mg, 0.5 mmol, 1 equiv.) was added, the mixture
was cooled to 08C and treated with propene 10 (0.5
mmol) in Me2CO (0.5 ml) in one batch. The resulting
heterogeneous slurry was stirred vigorously at 08C for
24 h, Na2SO3 (750 mg) was added and the mixture
was allowed to warm to rt and stirred for 30 min.
EtOAc (30 ml) was added and the organic layer was
separated; the aq. phase was further extracted with
EtOAc (3 Â 15 ml), the combined extracts were dried
(Na2SO4), evaporated to dryness and the mixture sep-
arated by PLC in benzene-Me2CO (9:1) to give the
syn-diol 11a as a colourless oil (Rf 0.12, 79%); dH 7.33
(d, J 8.9, H-2',6'), 7.05 (d, J 8.9, H-3',5'), 7.04 (d, J
8.4, H-60), 6.79 (d, J 2.3, H-30), 6.67 (dd, J 8.4 and
2.3, H-50), 5.19, 5.15, 5.13 (3 Â s, OCH2OCH3), 4.49
(dd, J 4.4 and 3.0, H-1), 3.93 (m, H-2), 3.49, 3.48, 3.43
(3 Â s, OCH2OCH3), 3.03 (d, J 4.4, 1-OH), 2.76 (dd, J
3.3.3. (2S,3S )-4',7-Dihydroxy¯avan-3-ol 5
dH and dC (Table 1); CD: Demax [l (nm)] +2500
(274), 1200 (238) (found: M+, 258.0897. C15H14O4
requires M+, 258.0893).
3.3.4. (2R,3R)-4',7-Dihydroxy¯avan-3-ol 4
CD: Demax [l (nm)]= 2500 (272), +1000 (238). The
1H and 13C NMR spectral data corresponded to those
indicated for 5 (Found: M+, 258.0884. C15H14O4
requires M+, 258.0893).
Acknowledgements
Financial support by the Foundation for Research
Development, Pretoria and by the `Sentrale
Navorsingsfonds' of UOFS is acknowledged.

1158
R.J.J. Nel et al. / Phytochemistry 52 (1999) 1153±1158
Roux, D. G., & De Bruyn, G. C. (1963). Condensed Tannins 17: iso-
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