Asymmetric synthesis of 4′-epi-trachycladines A and B

Article abstract of DOI:10.1055/s-2005-918439

The first asymmetric synthesis of 4′-epi-trachycladines A and B is reported. Starting from 2,2-dimethyl-1,3-dioxan-5-one the title nucleosides were synthesised in 14 steps employing the SAMP-/RAMP-hydrazone methodology. The dioxanone-SAMP-hydrazone was first transformed into a trisubstituted derivative by a triple α-/α′-alkylation. Removal of the chiral auxiliary and subsequent reduction gave the corresponding alcohol, which could be transformed over four steps into TBS-protected 2′-C-methyl-5′-deoxy- L-lyxose. The trachycladines were then obtained via the corresponding triacetate using standard Vorbrueggen and silyl-Hilbert-Johnson conditions in an overall yield of 18-21%. Such 2′-C-branched ribonucleosides are potential agonists for adenosine receptors and play an important role in drug discovery. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-918439

PAPER
3239
Asymmetric Synthesis of 4¢-epi-Trachycladines A and B
A
symmetric Synth
i
esis of
e
4
¢
-
epi
-
Tra
c
t
hycladi
e
nes
A
and Br Enders,* Irene Breuer, Eugen Drosdow
Institut für Organische Chemie, RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany
Fax +49(241)8092127; E-mail: enders@rwth-aachen.de
Received 30 August 2005
Dedicated to Professor Steven Ley on the occasion of his 60th birthday
O
N
NH2
Abstract: The first asymmetric synthesis of 4¢-epi-trachycladines
A and B is reported. Starting from 2,2-dimethyl-1,3-dioxan-5-one
the title nucleosides were synthesised in 14 steps employing the
SAMP-/RAMP-hydrazone methodology. The dioxanone-SAMP-
hydrazone was first transformed into a trisubstituted derivative by a
triple a-/a¢-alkylation. Removal of the chiral auxiliary and subse-
quent reduction gave the corresponding alcohol, which could be
transformed over four steps into TBS-protected 2¢-C-methyl-5¢-
deoxy-L-lyxose. The trachycladines were then obtained via the cor-
responding triacetate using standard Vorbrüggen and silyl-Hilbert–
Johnson conditions in an overall yield of 18–21%. Such 2¢-C-
branched ribonucleosides are potential agonists for adenosine re-
ceptors and play an important role in drug discovery.
N
N
N
N
NH
N
H3C
O
H3C
O
H3C
H3C
N
Cl
OH OH
trachycladine B (1b)
OH OH
trachycladine A (1a)
Figure 1
As is shown in the retrosynthetic analysis (Scheme 1), the
Key words: nucleosides, asymmetric synthesis, hydrazones, qua- title nucleosides 2a and 2b may be synthesised from the
sugar triacetate 3 under Vorbrüggen8 (2a) or silyl-
ternary stereocenters, Vorbrüggen coupling
Hilbert–Johnson9 (2b) conditions. Compound 3 can be
traced back to the parent 2¢-C-methyl-5¢-deoxy-L-lyxose
(4), which should be obtainable from the selectively pro-
tected tetrol 5. A retro-reduction leads to the ketone 6 and
based on the SAMP-/RAMP-hydrazone methodology10 to
the commercially available dioxanone 7.11
Nucleoside-type natural products play an important role
as models in drug development and in medicinal chemis-
try for the treatment of diseases like cancer, fungal, bacte-
rial and viral infections.1 In particular, marine organisms
are the source of a great variety of these compounds.2 In
1995 Molinski and Searle isolated the nucleosides trachy-
cladines A (1a) and B (1b) from the sponge Trachycladus
laevispirulifer Carter (Axinellida, Trachycladidae) col-
lected at Exmouth Gulf, Western Australia (Figure 1).3
Trachycladine A (or kumusine) has also been isolated
from the marine sponges Theonella Cupola and Theonella
sp.4 Both nucleosides contain the previously undescribed
sugar moiety 2¢-C-methyl-5¢-deoxy-D-ribose. Additional-
ly trachycladine A is an analogue of 2-chloro-2¢-deoxyad-
enosine which combines a remarkable activity against
hairy cell leukaemia and low toxicity in clinical trials.5
Trachycladine A shows in vitro cytotoxicity against sev-
eral human cell lines including leukaemia (CCRF-CEM),
colon tumour (HCT-116) and breast tumour cells (MCF-
7).3 Biological testing of trachycladine B could not be per-
formed due to its insufficient availability. The trachycla-
dines A and B have not been synthesised so far.
Thus, our synthetic route started with 2,2-dimethyl-1,3-
dioxan-5-one employing the SAMP-/RAMP-hydrazone
methodology.10,12 As previously reported for the RAMP-
hydrazone of 7 the enantiomeric SAMP-hydrazone of 7
was alkylated twice with MeI at the a- and a¢-positions.13
Subsequent a-alkylation with benzyloxymethyl chloride
(BOMCl) afforded the trisubstituted hydrazone 8 in very
good overall yield (68% over 4 steps), and excellent dia-
stereo- and enantiomeric excesses (de, ee ≥ 96%). Next
the chiral auxiliary was removed by ozonolysis in 63%
yield. In the following step, the racemisation-prone ke-
tone 6 was reduced with L-Selectride® to the correspond-
ing alcohol 5 with high diastereoselectivity and
quantitative yield (Scheme 2).
In our first approach to the desired 2¢-C-methyl-5¢-deoxy-
L-lyxose (4) we planned to establish a route via the 1,2-
diol 10. As is depicted in Scheme 3, the alcohol 5 could be
transformed into the 1,3-dioxolane 9 by using camphor-
sulfonic acid (CSA) in dry acetone in 86% yield. In the
following step, the removal of the benzyl protecting group
was performed by hydrogenation using 10% Pd/C. How-
ever, every attempt to oxidise the resulting 1,2-diol 10 to
the corresponding a-hydroxyaldehyde did not lead to the
desired product in acceptable yields.
It should be mentioned that structurally related 2¢-C-
branched ribonucleosides, which were prepared syntheti-
cally, act as potent anti-viral agents6 as well as selective
agonists for adenosine receptors.7
Therefore, our second approach involved a different pro-
tecting group strategy. The secondary hydroxyl group of
the alcohol 5 was protected as TBS-ether 11 under stan-
SYNTHESIS 2005, No. 19, pp 3239–3244
Advanced online publication: 25.10.2005
DOI: 10.1055/s-2005-918439; Art ID: C05805SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
5

3240
D. Enders et al.
PAPER
NH2
N
N
H3C
N
N
Cl
O
OH
O
O
H3C
CH3
CH3
OH OH
CH3
H3C
H3C
CH3
OBn
OBn
O
O
2a
OAc
OH
O
O
O
O
O
O
H3C
H3C
O
OAc OAc
OH OH
H3C CH3
H3C CH3
H3C CH3
N
3
4
NH
5
6
7
H3C
N
O
N
SAMP-hydrazone
methodology
H3C
OH OH
2b
Scheme 1 Retrosynthetic analysis of 4¢-epi-trachycladines A (2a) and B (2b).
O
OH
nate (DMP) generated 93% of the air-sensitive aldehyde
13 (Scheme 4).
H3C
CH3
OBn
5 steps
43%
Initial attempts to convert the aldehyde 13 directly to the
2-C-methyl-5-deoxy-L-lyxose by cleavage under strong
acidic conditions led to a mixture of products. Therefore,
a stepwise deprotection of 13 was performed. The selec-
tive cleavage of the acetonide protecting group was
achieved by treatment with diluted CSA in MeOH to give
a mixture of TBS-protected sugars 14 and 15 in 85%
yield. Unfortunately, all attempts to acylate the sugar 14
directly to the corresponding TBS-protected diacetate
failed. Merely small amounts of triacetate 3 were isolated
when the acylation step was performed under acidic con-
ditions. Thus, we concluded that the acylation of the ter-
tiary hydroxyl group of the sugar 14 is hindered by its
sterically demanding TBS-group. Therefore, the crude
mixture of 14 and 15 was deprotected with TBAF in THF.
O
O
O
O
H3C CH3
H3C CH3
5
7
(de, ee > 96%)
a–d10a
OCH3
68%
quant.
f
N
O
O
N
e10a
63%
H3C
CH3
OBn
H3C
CH3
OBn
O
O
O
H3C CH3
H3C CH3
6
8
(de, ee > 96%)
OR1
OTBS
Scheme 2 Asymmetric synthesis of 5. Reagents and conditions: a)
SAMP, C6H6, 70 °C, 3.5 h; b) 1. t-BuLi, THF, –78 °C, 2. MeI, –100
°C to r.t.; c) 1. t-BuLi, THF, –78 °C, 2. MeI, –100 °C to r.t.; d) 1.
t-BuLi, THF, –78 °C, 2. BOMCl, –100 °C to r.t.; e) O3, CH2Cl2, –78
°C, 5 min; f) L-Selectride®, THF, –78 °C.
CH3
CH3
R2
H3C
H3C
OBn
b
O
O
O
O
87%
H3C CH3
H3C CH3
5, R1 = H
12, R2 = CH2OH
13, R2 = CHO
a
c
96%
93%
dard conditions. An attempt to cleave the benzyl protect-
ing group of compound 11 using 10% Pd/C afforded the
1,2-diol 10, due to some acidic traces in the catalyst.
Therefore, the deprotection step was performed under
Birch conditions and gave the primary alcohol 12 in 87%
yield. Subsequent oxidation with Dess–Martin periodi-
11, R1 = TBS
CH3
O
OH
H3C
TBSO OH
CH3
O
14
d
85%
e, f
87%
OAc
OH
OH
OBn
OH
H3C
CH3
O
H3C
H3C
OH
OAc OAc
H3C
H3C
CH3
OTBS
H3C
3
OBn
a
H
H
b
H3C
OH OH
O
O
O
O
O
O
96%
86%
15
H3C CH3
H3C CH3
H3C CH3
Scheme 4 Preparation of the triacetate 3. Reagents and conditions:
a) 2,6-Lutidine, TBSOTf, CH2Cl2, 0 °C, 8 h; b) Ca/NH3, –33 °C, 3 h;
c) DMP, pyridine, CH2Cl2, r.t., 5 h; d) CSA, MeOH, r.t., 1.5 h; e)
TBAF, THF, r.t., 1 h; f) Ac2O, pyridine, 100 °C, 2.5 h.
5
9
10
Scheme 3 Preparation of the 1,2-diol 10. Reagents and conditions:
a) CSA, acetone, r.t., 2 h; b) 10% Pd/C, MeOH, r.t., 14 h.
Synthesis 2005, No. 19, 3239–3244 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of 4¢-epi-Trachycladines A and B
3241
NH2
The resulting sugar was directly transformed to the corre-
sponding triacetate 3. Due to very low reactivity of the ter-
tiary C-2 hydroxyl group very harsh acylation conditions
had to be employed.
N
N
8
H
N
N
Cl
H
H3C
O
H
4'
Finally, as shown in Scheme 5, coupling of the triacetate
2'
3'
H3C
3
with 2,6-dichloropurine was performed under
OH OH
Vorbrüggen conditions8 to afford 16a in a good yield. A
similar coupling of 2,6-dichloropurine with a 2-C-methyl-
D-ribose derivative has been described in the literature.7a
Next, deprotection of 16a as well as the substitution of the
6-chloro functionality was performed in methanolic NH3
and gave the desired 4¢-epi-trachycladine A (2a) in 97%
yield (de, ee ≥ 96%).
4'-epi-trachycladine A (2a)
Figure 2 NOESY interactions between H-8 and C-2¢-CH3, H-3¢ and
H-4¢ in 2a.
In conclusion, we have carried out the first asymmetric
synthesis of 4¢-epi-trachycladines A and B by employing
the SAMP-/RAMP-hydrazone methodology in key steps.
The total yield over 14 steps starting from the commer-
cially available dioxanone 7 was 18–21% and the title nu-
cleosides were obtained as virtually pure stereoisomers.
Cl
N
N
H3C
N
O
N
Cl
b
97%
Cl
N
All moisture-sensitive reactions were carried out using standard
Schlenk techniques unless stated otherwise. All reagents were pur-
chased from common commercial suppliers and used from freshly
opened containers. Solvents for flash chromatography and for
workup were dried and purified by conventional methods prior to
use. THF was freshly distilled from sodium/lead and benzophenone
under Ar. Preparative flash column chromatography was carried out
with Merck silica gel 60 (particle size 0.040–0.063 mm). Optical ro-
tation values were measured with a Perkin-Elmer P 241 polarime-
ter. IR spectra were taken with a Perkin-Elmer FT/IR 1760
spectrometer. NMR spectra were recorded on Varian Mercury 300,
Varian Inova 400 and Varian Unity 500 instruments; TMS was used
as internal standard. Mass spectra were acquired on a Varian MAT
212 (EI, 70 eV, 1 mA) and a Finnigan MAT SSQ 7000 (CI, 100 eV)
spectrometer. Microanalyses were obtained with a Vario EL ele-
ment analyzer. HRMS measurements were performed on a Finnigan
MAT, MAT 95 instrument. Merck silica gel TLC plates 60 F254
have been used for TLC analyses. Melting points were determined
on a Tottoli melting point apparatus and are uncorrected. The com-
pounds 5, 6 and 8 have already been reported as enantiomers.10a
H3C
N
NH2
a
84%
OAc OAc
N
N
N
16a
N
N
H
Cl
H3C
O
N
Cl
H3C
OH OH
CH3
O
2a (de, ee > 96%)
OAc
O
H3C
OAc OAc
N
NH
3
H3C
N
N
O
O
N
H3C
O
N
OH OH
N
N
N
NH
2b (de, ee > 96%)
NH
c
70%
H3C
O
N
H
d
92%
H3C
OAc OAc
(S)-1-(Benzyloxy)-2-[(4R,5S)-2,2,5-trimethyl-1,3-dioxolan-4-
yl]propan-2-ol (9)
16b
To a stirred solution of the alcohol 5 (0.49 g, 1.75 mmol) in dry ac-
etone (40 mL) a solution of CSA (13 mg, 0.056 mmol) in dry ace-
tone (9.0 mL) was added slowly. After stirring for 2.5 h at ambient
temperature, sat. NaHCO3 (1.0 mL) was added and the solvent was
removed under reduced pressure. The oily residue was partitioned
between water (5 mL) and Et2O (50 mL) and the aqueous layer ex-
tracted with Et2O (2 × 50 mL). Evaporation of the solvent and puri-
fication by flash chromatography (silica gel, Et2O–hexane, 1:5)
yielded 9 as a colourless oil (0.42 g, 86%); de, ee ≥96%; [a]D25 –2.3
(c = 1.03, CHCl3).
Scheme 5 Final steps of the 4¢-epi-trachycladine synthesis.
Reagents and conditions: a) TMSOTf, DBU, MeCN, r.t., 1.5 h; b)
NH3, MeOH, r.t., 24 h; c) 1. BSA, MeCN, 70 °C, 1 h; 2. TMSOTf,
DBU, MeCN, 75 °C, 1 h; d) NH3, MeOH, r.t., 24 h.
The a-configuration of the nucleoside 2a was confirmed
by NOESY measurements, which showed an interaction
of H-8 with the H-3¢, H-4¢ and C-2¢-CH3 protons
(Figure 2).
IR (film): 3492, 2983, 2932, 1455, 1374, 1247, 1217, 1174, 1081,
863, 742, 699 cm–1.
In a similar way, the triacetate 3 was coupled with in situ
silylated hypoxanthine14 employing standard silyl- 1H NMR (300 MHz, CDCl3): d = 1.24 [s, 3 H, C(OH)CH3], 1.34 (d,
Hilbert–Johnson conditions.9 The configuration of the
J = 5.9 Hz, 3 H, OCHCH3), 1.37 [s, 3 H, C(CH3)CH3], 1.40 [s, 3 H,
C(CH3)CH3], 2.50 (br s, 1 H, OH), 3.36 [d, J = 9.1 Hz, 1 H,
product was confirmed by NOESY and HC-HMBC mea-
C(OH)CH2], 3.50 [d, J = 9.1 Hz, 1 H, C(OH)CH2], 3.67 [d, J = 8.2
surements as well as by comparison of its 13C NMR sig-
Hz, 1 H, OCHC(OH)CH3], 4.15 (dq, J = 5.9, 8.2 Hz, 1 H,
nals with those of inosine.15 Finally, deprotection of the
diacetate 16b with NH3 in MeOH afforded the title com-
pound 2b as a colourless solid (de, ee ≥ 96%).
OCHCH3), 4.56 (s, 2 H, OCH2Ph), 7.39–7.28 (m, 5 H, Ph).
13C NMR (75 MHz, CDCl3): d = 19.9 (OCHCH3), 20.4
[C(OH)CH3], 27.0 [C(CH3)CH3], 27,4 [C(CH3)CH3], 71.9
[C(OH)CH3], 72.8 (OCHCH3), 73.4 (OCH2Ph), 75.2 [C(OH)CH2],
Synthesis 2005, No. 19, 3239–3244 © Thieme Stuttgart · New York

3242
D. Enders et al.
PAPER
84.3 [OCHC(OH)CH3], 107.9 [C(CH3)CH3], 127.6 (CPh), 127.7
(p-CPh), 128.4 (CPh), 137.9 (CPh).
MS (EI, 70 eV): m/z (%) = 235 (14), 215 (16), 187 (12), 173 (27),
172 (69), 131 (17), 115 (63), 92 (10), 91 (100), 75 (11), 73 (17).
MS (EI, 70 eV): m/z (%) = 281 (1) [M]+, 265 (14), 222 (4), 204 (3),
165 (21), 115 (27), 101 (11), 91 (100), 59 (24).
Anal. Calcd for C22H38O4Si (394.62): C, 66.96; H, 9.71. Found: C,
67.28; H, 9.21.
Anal. Calcd for C16H24O4 (280.17): C, 68.54; H, 8.63. Found: C,
68.64; H, 8.18.
[(4S,5R,6S)-5-(tert-Butyldimethylsilyloxy)-2,2,4,6-tetramethyl-
1,3-dioxan-4-yl]methanol (12)
To a deep blue solution of calcium (0.27 g, 3.48 mmol) in liquid
NH3 (40 mL) benzylether 11 in THF (2 mL) was added. The result-
ing solution was refluxed for 3 h. Some solid NH4Cl was added to
the reaction mixture until the disappearance of the blue colour. The
mixture was warmed to r.t. and the residue was taken up in water
(10 mL). The aqueous phase was extracted with Et2O (3 × 50 mL).
The combined organic layer was dried (MgSO4) and concentrated
to a syrup, which was passed through silica gel (Et2O–hexane, 1:10
followed by 1:5) to give 12 (0.18 g, 87%); de, ee ≥ 96% (NMR);
[a]D24 –11.5 (c = 1.34, CHCl3).
(S)-2-[(4R,5S)-2,2,5-Trimethyl-1,3-dioxolan-4-yl]propane-1,2-
diol (10)
To a solution of 1,3-dioxolane 9 (0.12 g, 0.43 mmol) in MeOH (12
mL) 10% Pd/C was added and stirred under H2 at atmospheric pres-
sure for 14 h. Removal of the catalyst, evaporation of the solvent
and chromatographic purification of the product (silica gel, EtOAc–
CH2Cl2–MeOH, 25:75:3) afforded the 1,2-diol 10 as colourless
23
crystals; yield: 0.08 g (96%); de, ee ≥ 96% (NMR); mp 51 °C; [a]D
+6.0 (c = 1.04, CHCl3).
IR (film): 3415, 2987, 2935, 2907, 1460, 1374, 1251, 1214, 1174,
1055, 984, 861, 801, 680, 599 cm–1.
IR (CHCl3): 3508, 2987, 2936, 2860, 1467, 1375, 1253, 1184, 1099,
983, 868, 840, 775 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.22 [s, 3 H, C(OH)CH3], 1.36 (d,
J = 6.0 Hz, 3 H, OCHCH3), 1.40 [s, 3 H, C(CH3)CH3], 1.41 [s, 3 H,
C(CH3)CH3], 2.20 (m, 1 H, CH2OH), 2.51 [s, 1 H, C(CH3)OH], 3.46
[dd, J = 10.1, 6.6 Hz, 1 H, CH2OH], 3.61 [d, J = 8.2 Hz, 1 H,
OCHC(OH)CH3)], 3.69 (dd, J = 11.1, 4.5 Hz, 1 H, CH2OH), 4.11
(dq, J = 6.0, 8.0 Hz, 1 H, OCHCH3).
13C NMR (100 MHz, CDCl3): d = 20.0 (OCHCH3), 20.8
[C(OH)CH3], 26.9 [C(CH3)CH3], 27.3 [C(CH3)CH3], 67.5
[C(OH)CH2], 71.8 [C(OH)CH3], 72.8 (OCHCH3), 85.8
[OCHC(OH)CH3], 107.8 [C(CH3)CH3].
1H NMR (400 MHz, CDCl3): d = 0.06 [s, 3 H, Si(CH3)CH3], 0.08
[s, 3 H, Si(CH3)CH3], 0.92 [s, 9 H, C(CH3)3], 1.22 (d, J = 6.6 Hz, 3
H, CHCH3), 1.27 [s, 3 H, C(CH3)CH2O], 1.35 [d, J = 0.6 Hz, 3 H,
C(CH3)CH3], 1.44 [d, J = 9.6 Hz, 3 H, C(CH3)CH3], 2.06 (dd, J =
9.6, 3.6 Hz, 1 H, CH2OH), 3.28–3.40 (m, 2 H, CH2OH), 4.01 (d,
J = 5.8 Hz, 1 H, CHOSi), 4.11–4.18 (m, 1 H, CHCH3).
13C NMR (100 MHz, CDCl3): d = –4.7 [Si(CH3)CH3], –4.2
[Si(CH3)CH3], 17.1 (CHCH3), 18.1 [C(CH3)3], 20.1 (CCH3), 25.9
[C(CH3)3], 26.0 [C(CH3)CH3], 30.1 [C(CH3)CH3], 68.0 [CCH2OH,
CHCH3, CHOSi(CH3)2], 77.4 (CCH3), 99.4 [C(CH3)CH3].
MS (CI, isobutane): m/z (%) = 192 (4), 191 (37) [M + H]+, 173 (7),
133 (29), 115 (100), 97 (13).
MS (CI, methane): m/z (%) = 305 (7) [M + 1]+, 289 (12), 247 (16),
231 (19), 230 (19), 229 (100), 189 (15), 187 (28), 186 (11), 185
(63), 173 (24), 172 (19), 145 (23), 115 (14), 97 (10).
Anal. Calcd for C9H18O4 (190.12): C, 56.82; H, 9.54. Found: C,
56.64; H, 9.55.
MS (EI, 70 eV): m/z (%) = 173 (15), 172 (50), 145 (73), 133 (11),
131 (14), 116 (14), 115 (100), 75 (68), 73 (25).
[(4S,5R,6S)-4-(Benzyloxymethyl)-2,2,4,6-tetramethyl-1,3-diox-
an-5-yloxy](tert-butyl)dimethylsilane (11)
Anal. Calcd for C15H32O4Si (304.5): C, 59.17; H, 10.59. Found: C,
59.45; H, 10.62.
The alcohol 5 (0.23 g, 0.79 mmol) was dissolved in CH2Cl2 (2.5
mL) and 2,6-lutidine (0.17 g, 1.58 mmol) was added at 0 °C. The
reaction mixture was stirred for 15 min at this temperature and treat-
ed dropwise with TBSOTf (0.72 g, 1.03 mmol). After being stirred
at 0 °C for 8 h, the reaction mixture was poured into water (10 mL)
and the aqueous phase was extracted with Et2O (3 × 50 mL). The
combined organic layers were dried over MgSO4 and the solvent
was removed under reduced pressure. Flash chromatography (silica
gel, Et2O–hexane 1:9) afforded 11 as a colourless oil (0.30 g, 96%);
de, ee ≥ 96% (NMR); [a]D24 –4.7 (c = 1.17, CHCl3).
(4R,5R,6S)-5-(tert-Butyldimethylsilyloxy)-2,2,4,6-tetramethyl-
1,3-dioxane-4-carbaldehyde (13)
To a solution of alcohol 12 (0.27 g, 0.89 mmol) in CH2Cl2 (26 mL)
pyridine (0.76 mL, 0.74 g, 9.3 mmol) was added. The solution was
treated dropwise with DMP (1.07 g, 2.52 mmol) in CH2Cl2 (12 mL)
and stirred for 5 h at ambient temperature. Sat. NaHCO3 (10 mL)
and Na2S2O3 (2 mL) were added and the mixture was stirred for 15
min. The aqueous layer was separated and extracted with Et2O (3 ×
50 mL). The combined organic phases were washed with brine (10
mL), dried (MgSO4) and concentrated under reduced pressure. Pu-
rification by flash chromatography (silica gel, Et2O–hexane, 1:10)
gave 13 as an air-sensitive colourless liquid (0.25 g, 93%); de, ee ≥
96% (NMR); [a]D24 –48.8 (c = 0.70, CHCl3).
IR (CHCl3): 2988, 2934, 2891, 2859, 1468, 1371, 1251, 1210, 1184,
1107, 1012, 989, 865, 838, 775 cm–1.
1H NMR (400 MHz, C6D6): d = 0.02–0.10 [m, 6 H, Si(CH3)2], 1.01
[s, 9 H, C(CH3)3], 1.27 (d, J = 6.3 Hz, 3 H, CHCH3), 1.40 [s, 3 H,
C(CH3)CH2O], 1.50 [s, 3 H, C(CH3)CH3], 1.58 [s, 3 H,
C(CH3)CH3], 3.36 [s, 2 H, C(CH3)CH2O], 4.00 [m, 1 H, CHO-
Si(CH3)2], 4.09 (m, 1 H, CHCH3), 4.45 (s, 2 H, OCH2Ph), 7.13–7.32
(m, 5 H, Ph).
13C NMR (100 MHz, C6D6): d = –4.4 [Si(CH3)CH3], –4.1
[Si(CH3)CH3], 17.8 (CHCH3), 18.3 [C(CH3)3], 21.6 (CCH3), 26.2
[C(CH3)3], 27.3 [C(CH3)CH3], 30.1 [C(CH3)CH3], 66.5 (CHCH3),
69.5 [CHOSi(CH3)2], 73.2 (OCH2Ph), 75.8 (CCH2O), 77.5 (CCH3),
98.9 [C(CH3)CH3], 127.3 (o-CPh), 128.2 (m-CPh, p-CPh), 138.7
(CPh).
IR (film): 2937, 2896, 1730, 1467, 1371, 1258, 1202, 1160, 1117,
1059, 1006, 863, 839, 776, 685 cm–1.
1H NMR (300 MHz, C6D6): d = 0.00 [s, 3 H, Si(CH3)CH3], 0.02 [s,
3 H, Si(CH3)CH3], 1.06 [s, 9 H, C(CH)3], 1.17 (s, 3 H, CH3), 1.54
[s, 3 H, C(CH3)CH3], 3.85–3.39 (m, 2 H, CHCH3, CHOSi), 9.64 (s,
1 H, CHO).
13C NMR (75 MHz, C6D6): d = –5.0 [Si(CH3)CH3], –4.8
[Si(CH3)CH3], 17.2 (CHCH3), 17.4 [C(CH3)3], 19.7 (CCH3), 22.5
[C(CH3)CH3], 25.0 [C(CH3)3], 29.4 [C(CH3)CH3], 65.0, 65.9
(CHCH3, CHOSi), 80.7 (CCH3), 97.9 [C(CH3)CH3], 203.2 (C=O).
MS (CI, methane): m/z (%) = 393 (1) [M – 1]+, 379 (12), 337 (14),
279 (13), 245 (28), 235 (15), 230 (19), 229 (100), 215 (14), 213
(10).
MS (EI, 70 eV): m/z (%) = 416 (39), 273 (10), 229 (20), 215 (31),
187 (17), 172 (62), 159 (24), 143 (26), 131 (33), 115 (100).
Synthesis 2005, No. 19, 3239–3244 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of 4¢-epi-Trachycladines A and B
3243
Anal. Calcd for C15H30O4Si (302.5): C, 59.55; H, 10.00. Found: C,
59.63; H, 10.23.
(s, 3 H, COCH3), 4.48 (dq, J = 6.4, 4.4 Hz, 1 H, H-4), 5.37 (d, J =
4.4 Hz, 1 H, H-3), 6.36 (s, 1 H, H-1).
13C NMR (100 Hz, CDCl3): d = 14.8 (C-5), 17.5 (C-2-CH3), 20.5
(COCH3), 21.1 (COCH3), 21.4 (COCH3), 75.8 (C-3), 77.8 (C-4),
86.0 (C-2), 98.8 (C-1) 169.1 (COCH3), 169.3 (COCH3), 169.5
(COCH3).
3-(tert-Butyldimethylsilyloxy)-2-C-methyl-5-deoxy-L-lyxo-
furanose (14)
To a solution of the aldehyde 13 (0.23 g, 0.77 mmol) in MeOH (18
mL), a solution of CSA (3.8 mg, 0.016 mmol) in MeOH (3.8 mL)
was added slowly. After 1.5 h at ambient temperature solid
NaHCO3 (10 mg) was added and the mixture was stirred for an ad-
ditional 30 min. The solution was filtered and concentrated under
reduced pressure. The syrupy residue was purified by chromatogra-
phy (silica gel, EtOAc–hexane 2:1) to give a mixture of 14 and 15
(0.17 g, 85%) as a colourless oil. A small sample of 14 was purified
by flash chromatography for spectroscopic data; de, ee ≥ 96%; a/b-
ratio in C6D6: 1:4 (NMR).
Minor Diastereomer
1H NMR (400 Hz, CDCl3): d = 1.25 (d, J = 6.3 Hz, 3 H, H-5), 1.60
(s, 3 H, C-2-CH3), 2.03 (s, 3 H, COCH3), 2.06 (s, 3 H, COCH3), 2.12
(s, 3 H, COCH3), 4.48 (dq, J = 6.4, 5.0 Hz, 1 H, H-4), 5.38 (d, J =
5.0 Hz, 1 H, H-3), 6.22 (s, 1 H, H-1).
13C NMR (100 Hz, CDCl3): d = 16.0 (C-5), 17.5 (C-2-CH3), 21.0
(COCH3), 21.1 (COCH3), 21.4 (COCH3), 75.0 (C-4), 76.8 (C-3),
86.0 (C-2), 97.6 (C-1), 168.7 (COCH3), 169.3 (COCH3), 169.5
(COCH3).
IR (film): 3402, 2934, 2860, 1466, 1382, 1257, 1207, 1156, 1055,
843, 779, 675 cm–1.
MS (EI, 70 eV): m/z (%) = 241 (1), 215 (100) [M – OAc]+, 172 (14),
145 (36), 126 (9), 113 (48), 103 (32), 84 (89), 69 (60).
MS (CI, isobutane): m/z = 217 (2), 216 (11), 215 (100) [M – OAc]+.
Major Diastereomer
1H NMR (500 Hz, C6D6): d = 0.00 [s, 3 H, Si(CH3)CH3], 0.10 [s, 3
H, Si(CH3)CH3], 0.94 [s, 9 H, C(CH3)3], 1.16 (s, 3 H, C-2-CH3),
1.29 (d, J = 6.7 Hz, 3 H, H-5), 3.24 (s, 1 H, C-2-OH), 3.37 (d, J =
4.3 Hz, 1 H, H-3), 3.49 (d, J = 10.7 Hz, 1 H, C-1-OH), 3.85 (dq, J =
6.7, 4.4 Hz, 1 H, H-4), 4.89 (d, J = 10.4 Hz, 1 H, H-1).
Anal. Calcd for C12H18O7 (274.11): C, 52.55; H, 6.62. Found: C,
52.57; H, 6.68.
2,6-Dichloro-9-(2¢,3¢-di-O-acetyl-2¢-C-methyl-5¢-deoxy-a-L-lyx-
ofuranosyl)purine (16a)
13C NMR (100 Hz, C6D6): d = –4.9 [Si(CH3)CH3], –4.7
[Si(CH3)CH3], 17.1 (C-2-CH3), 18.3 [SiC(CH3)3], 22.3 (C-5), 25.8
[SiC(CH3)3], 76.3 (C-4), 76.8 (C-2), 78.5 (C-3), 101.6 (C-1).
To a stirred solution of 2,6-dichloropurine (86 mg, 0.46 mmol), tri-
acetate 3 (61 mg, 0.22 mmol) and DBU (154 mg, 1.00 mmol) in dry
MeCN (3.0 mL) cooled to –15 °C was slowly added a solution of
TMSOTf (640 mg, 2.88 mmol) in dry MeCN (3.3 mL). The reaction
mixture was allowed to warm to ambient temperature, stirred for
further 1.5 h and quenched with sat. NaHCO3 (20 mL) at 0 °C. The
aqueous phase was extracted with CH2Cl2 (4 × 100 mL), washed
with brine (20 mL) and dried over MgSO4. Removal of the solvent
under reduced pressure and purification of the residue by flash chro-
matography (silica gel, EtOAc–hexane, 1:2) afforded pure crystal-
line 15 (74 mg, 84%); de, ee ≥ 96% (NMR); mp 112 °C; [a]D24 –46.1
(c = 1.15, CHCl3).
Minor Diastereomer
1H NMR (500 Hz, C6D6): d = –0.04 [s, 3 H, Si(CH3)CH3], 0.01 [s,
3 H, Si(CH3)CH3], 0.94 [s, 9 H, C(CH3)3], 1.37 (d, J = 6.7 Hz, 3 H,
H-5), 1.50 (s, 3 H, C-2-CH3), 2.65 (d, J = 3.4 Hz, 1 H, C-1-OH),
3.08 (s, 1 H, C-2-OH), 4.03 (d, J = 6.4 Hz, 1 H, H-3), 4.42 (dq, J =
6.7, 6.6 Hz, 1 H, H-4), 5.35 (d, J = 3.1 Hz, 1 H, H-1).
13C NMR (100 Hz, C6D6): d = –4.9 [Si(CH3)CH3], –4.7
[Si(CH3)CH3], 16.9 (C-2-CH3), 18.3 [SiC(CH3)3], 21.4 (C-5), 25.8
[SiC(CH3)3], 75.7 (C-4), 77.8 (C-3), 79.4 (C-2), 102.4 (C-1).
MS (EI, 70 eV): m/z (%): 245 (2) [M – OH]+, 229 (3), 201 (6), 187
(27), 159 (78), 143 (74), 115 (75), 103 (16), 84 (58), 75 (100).
IR (CHCl3): 3125, 3002, 2939, 1753, 1593, 1556, 1491, 1362, 1248,
1168, 1141, 1090, 919, 883, 803, 757 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.30 (d, J = 6.6 Hz, 3 H, H-5¢),
1.44 (s, 3 H, C-2¢-CH3), 2.10 (s, 3 H, COCH3), 2.20 (s, 3 H,
COCH3), 4.98 (dq, J = 6.5, 3.7 Hz, 1 H, H-4¢), 5.76 (d, J = 3.6 Hz,
1 H, H-3¢), 6.46 (s, 1 H, H-1¢), 8.30 (s, 1 H, H-8).
MS (ESI–): m/z (%) = 261 (10) [M – H]–, 262 (76).
Anal. Calcd for C12H26O4Si (262.16): C, 54.92; H, 9.99. Found: C,
54.47; H, 9.65.
13C NMR (100 MHz, CDCl3): d = 15.0 (C-5¢), 18.0 (C-2¢-CH3), 20.5
(COCH3), 21.1 (COCH3), 77.0 (C-3¢), 77.4 (C-4¢), 84.8 (C-2¢), 90.1
(C-1¢), 131.0 (C-5), 144.4 (C-8), 151.8, 152.4, 153.0, 168.9
(COCH3), 169.0 (COCH3).
MS (EI, 70 eV): m/z (%) = 342 (5) [M – HOAc]+, 282 (25), 215
(100), 188 (30), 153 (15), 113 (33), 101 (9), 95 (13).
1,2,3-Tri-O-Acetyl-2-C-methyl-5-deoxy-L-lyxo-furanose (3)
A mixture of the crude products 14 and 15 (0.32 g, 0.88 mmol) was
dissolved in THF (17 mL) and treated dropwise with 1.0 M TBAF
in THF (1.2 mL, 1.2 mmol). The reaction mixture was stirred at am-
bient temperature for 1 h and evaporated to dryness. The syrupy res-
idue was thoroughly dried under vacuum and dissolved in dry
pyridine (15 mL). Ac2O (8 mL) was slowly added and the reaction
mixture was stirred for 2.5 h at 100 °C. Solvent evaporation at am-
bient temperature under reduced pressure gave a yellow residue,
which was partitioned between sat. NaHCO3 (10 mL) and CH2Cl2
(50 mL). The aqueous layer was extracted with CH2Cl2 (3 × 50 mL)
and the organic phases were dried (MgSO4) and evaporated under
reduced pressure. Purification by flash chromatography (silica gel,
EtOAc–hexane, 1:2) yielded triacetate 3 as slightly yellowish crys-
tals (0.21 g, 87% over 2 steps); de, ee ≥ 96% (NMR); a/b-ratio: 8:1;
mp: 51 °C; [a]D25 –76.2 (c = 0.98, CHCl3).
MS (ESI+): m/z (%) = 529 (12), 425 (90) [M + Na]+, 297 (100), 255
(5), 215 (11).
HRMS: m/z calcd for [C15H16N4O5Cl2 – C2H4O2]: 342.0286; found:
342.0287.
2-Chloro-9-(2¢-C-methyl-5¢-deoxy-a-L-lyxofuranosyl)adenine
(2a)
A solution of 16a (30 mg, 0.075 mmol) in MeOH (5 mL) was satu-
rated with gaseous NH3 at –20 °C and stirred at r.t. in a sealed tube
for 24 h. The reaction mixture was evaporated in vacuo and the res-
idue was purified by flash chromatography (silica gel, EtOAc–
CH2Cl2–MeOH, 25:75:5) to give 2a as a colourless solid (22 mg,
97%); de, ee ≥ 96% (NMR); mp 97 °C; [a]D24 –32.6 (c = 0.92, ace-
tone).
IR (KBr): 3477, 2998, 2941, 1751, 1450, 1378, 1231, 1151, 1086,
1026, 915, 884, 837, 615, 523 cm–1.
Major Diastereomer
1H NMR (400 Hz, CDCl3): d = 1.20 (d, J = 6.6 Hz, 3 H, H-5), 1.63
(s, 3 H, C-2-CH3), 2.06 (s, 3 H, COCH3), 2.12 (s, 3 H, COCH3), 2.13
Synthesis 2005, No. 19, 3239–3244 © Thieme Stuttgart · New York

3244
D. Enders et al.
PAPER
IR (KBr): 3372, 3201, 1653, 1597, 1461, 1349, 1311, 1249, 1093,
1041, 940, 751, 684 cm–1.
MS (EI, 34 eV): m/z (%) = 266 (0.7) [M]+, 165 (4), 84 (92), 66
(100).
1H NMR (400 MHz, acetone-d6): d = 1.09 (s, 3 H, C-2¢-CH3), 1.33
(d, J = 6.6 Hz, 3 H, H-5¢), 3.32 (br s, 1 H, OH), 4.16 (d, J = 4.7 Hz,
1 H, H-3¢), 4.68 (br s, 1 H, OH), 4.77 (dq, J = 6.6, 6.6 Hz, 1 H, H-
4¢), 6.10 (s, 1 H, H-1¢), 7.10 (br s, 2 H, NH2), 8.14 (s, 1 H, H-8).
13C NMR (100 MHz, acetone-d6): d = 16.0 (C-5¢), 21.1 (C-2¢-CH3),
77.5 (C-3¢), 78.9 (C-4¢), 80.6 (C-2¢), 92.0 (C-1¢), 119.6 (C-5), 140.3
(C-8), 151.4 (C-4), 154.3 (C-2), 157.6 (C-6).
MS (ESI+): m/z (%) = 288 (2) [M – H + Na]+, 160 (3), 159 (100).
MS (ESI–): m/z (%) = 265 (2) [M – H]–, 136 (3), 135 (100), 97 (1).
HRMS: m/z calcd for C11H14N4O4: 266.1015; found: 266.1014.
Anal. Calcd for C11H14N4O4·12/3H2O (296.28): C, 44.59; H, 5.90, N,
18.91. Found: C, 44.43; H, 5.59, N, 18.50.
Acknowledgment
MS (EI, 70 eV): m/z (%) = 264 (1) [M – H3O2]+, 236 (2), 219 (1),
153 (2), 136 (2), 107 (1), 74 (14), 59 (100).
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 380, Graduiertenkolleg 440, scholarship for E.D.) and the
Fonds der Chemischen Industrie. We thank Degussa AG, BASF
AG, Bayer AG and Wacker Chemie for the donation of chemicals.
HRMS: m/z calcd for [C11H14N5O3Cl – H3O2]: 264.0652; found:
264.0652.
9-(2¢,3¢-Di-O-acetyl-2¢-C-methyl-5¢-deoxy-a-L-lyxofuranosyl)hy-
poxanthine (16b)
References
To a solution of hypoxanthine (66 mg, 0.48 mmol) in anhyd MeCN
(2.0 mL) BSA (0.30 mL, 0.25 g, 1.21 mmol) was added. The reac-
tion mixture was heated at 70 °C for 1 h and cooled to r.t. Triacetate
3 (40 mg, 0.15 mmol) dissolved in dry MeCN (2.0 mL) was added,
followed by DBU (120 mg, 0.79 mmol) in dry MeCN (2.0 mL). The
solution was cooled to –30 °C and TMSOTf (0.34 g, 1.52 mmol)
dissolved in dry MeCN (3.0 mL) was added dropwise. The solution
was heated under reflux for 1.5 h and poured into cold sat. NaHCO3
(10 mL). The mixture was extracted with CH2Cl2 (3 × 50 mL), the
organic phase was dried over MgSO4 and evaporated in vacuo. The
residue was purified by flash chromatography (silica gel, THF–hex-
ane, 9:1; then EtOAc–CH2Cl2–MeOH, 25:75:5) to give a colourless
solid, which could be further purified by preparative HPLC (Kro-
masil 100 Sil 7 mm, hexane–EtOH, 6:4); yield: 44 mg, 70%; de, ee
≥ 96% (NMR); mp 53 °C; [a]D25 –71.4 (c = 1.01, acetone).
(1) (a) Rachakonda, S.; Cartee, L. Curr. Med. Chem. 2004, 11,
775. (b) Newman, D. J.; Cragg, G. M. Curr. Med. Chem.
2004, 11, 1693.
(2) Reviews: (a) Knapp, S. Chem. Rev. 1995, 95, 1859.
(b) Zhang, D.; Miller, M. J. Curr. Pharm. Des. 1999, 5, 73.
(c) Isono, K. J. Antibiot. 1988, 41, 1711. (d) Isono, K.
Pharmacol. Ther. 1991, 52, 269.
(3) Searle, P. A.; Molinski, T. F. J. Org. Chem. 1995, 60, 4296.
(4) (a) Ichiba, T.; Nakao, Y.; Scheuer, P. J. Tetrahedron Lett.
1995, 36, 3977. (b) Erdogan, I.; Higa, T. J. Fac. Pharm.,
Ankara 2000, 29, 1.
(5) Jaiyesimi, I. A.; Kantarjian, H. M.; Estey, E. H. Cancer
1993, 72, 5.
(6) (a) Bio, M. M.; Xu, F.; Waters, M.; Williams, J. M.; Savary,
K. A.; Cowden, C. J.; Yang, C.; Buck, E.; Song, Z. J.;
Tschaen, D. M.; Volante, R. P.; Reamer, R. A.; Grabowski,
E. J. J. J. Org. Chem. 2004, 69, 6257. (b) Eldrup, A. B.;
Allerson, C. R.; Bennett, C. F.; Bera, S.; Bhat, B.; Bhat, N.;
Bosserman, M. R.; Brooks, J.; Burlein, C.; Carroll, S. S.;
Cook, P. D.; Getty, K. L.; MacCoss, M.; McMasters, D. R.;
Olsen, D. B.; Prakash, T. P.; Prhavc, M.; Song, Q.;
Tomassini, J. E.; Xia, J. J. Med. Chem. 2004, 47, 2283.
(7) (a) Franchetti, P.; Cappellacci, L.; Marchetti, S.; Trincavelli,
L.; Martini, C.; Mazzoni, M. R.; Lucacchini, A.; Grifantini,
M. J. Med. Chem. 1998, 41, 1708. (b) van Tilburg, E. W.;
van der Klein, P. A. M.; von Frijtag Drabbe Künzel, J.; de
Groote, M.; Stannek, C.; Lorenzen, A.; Ijzerman, A. P. J.
Med. Chem. 2001, 44, 2966.
IR (KBr): 3451, 3212, 3113, 3054, 2995, 2940, 1754, 1698, 1589,
1549, 1378, 1245, 1140, 1088, 1042, 1020, 891, 797, 607 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.29 (d, J = 6.9 Hz, 3 H, H-5¢),
1.40 (s, 3 H, C-2¢-CH3), 2.02 (s, 3 H, COCH3), 2.07 (s, 3 H,
COCH3), 4.93 (dq, J = 6.3, 3.6 Hz, 1 H, H-4¢), 5.75 (d, J = 3.6 Hz,
1 H, H-3¢), 6.17 (br s, 1 H, NH), 6.37 (s, 1 H, H-1¢), 8.05 (s, 1 H, H-
8), 8.20 (s, 1 H, H-2).
13C NMR (100 MHz, CDCl3): d = 15.0 (C-5¢), 17.7 (C-2¢-CH3), 20.5
(COCH3), 21.2 (COCH3), 77.0 (C-3¢), 77.1 (C-4¢), 85.0 (C-2¢), 89.8
(C-1¢), 124.6 (C-5), 139.2 (C-8), 145.1 (C-2), 148.5 (C-4), 158.7 (C-
6), 169.0 (COCH3).
MS (EI, 70 eV): m/z (%) = 350 (3) [M]+, 231 (3), 215 (100), 165 (3),
137 (8), 113 (28), 95 (5), 85 (8), 69 (4).
(8) Vorbrüggen, H.; Ruh-Pohlenz, C. Org. React. (N.Y.) 2000,
55, 1.
HRMS: m/z calcd for C15H18N4O6: 350.1226; found: 350.1224.
(9) (a) Hilbert, G. E.; Johnson, T. B. J. Am. Chem. Soc. 1930, 52,
4489. (b) Birkofer, L.; Ritter, A.; Kühltau, H.-P. Chem. Ber.
1964, 97, 934.
(10) (a) Enders, D.; Nühring, A.; Runsink, J.; Raabe, G. Synthesis
2001, 1406. (b) Nühring, A. PhD Dissertation; RWTH
Aachen: Germany, 2001.
(11) Reviews: (a) Enders, D.; Voith, M.; Lenzen, A. Angew.
Chem. Int. Ed. 2005, 44, 1304; Angew. Chem. 2005, 117,
1330. (b) Job, A.; Janeck, C. F.; Bettray, W.; Peters, R.;
Enders, D. Tetrahedron 2002, 58, 2253.
(12) Enders, D.; Breuer, I.; Raabe, G. Synthesis 2005, in press.
(13) Jegelka, U. PhD Dissertation; RWTH Aachen: Germany,
1992.
9-(2-C¢-Methyl-5¢-deoxy-a-L-lyxo-furanosyl)hypoxanthine (1b)
The diacetate 16b (30 mg, 0.086 mmol) was deprotected by the pro-
cedure described for the nucleoside 16a to give 4¢-epi-trachycladine
B (2b). The crude product was purified by flash chromatography
(silica gel, EtOAc–CH2Cl2–MeOH, 25:75:10) to yield 2b (21 mg,
23
92%) as a colourless solid; de, ee ≥ 96% (NMR); mp 172 °C; [a]D
–55.8 (c = 1.06, MeOH).
IR (KBr): 3426, 3134, 3053, 2937, 2899, 1691, 1591, 1548, 1462,
1220, 1080, 647, 600 cm–1.
1H NMR (300 MHz, CD3OD): d = 1.05 (s, 3 H, C-2¢-CH3), 1.34 (d,
J = 6.7 Hz, 3 H, H-5¢), 3.98 (d, J = 4.5 Hz, 1 H, H-3¢), 4.74 (dq, J =
6.4, 4.5 Hz, 1 H, H-4¢), 6.16 (s, 1 H, H-1¢), 8.05 (s, 1 H, H-8), 8.15
(s, 1 H, H-2).
(14) Moore, C. M.; Chiaramonte, M.; Higgins, T.; Kuchta, R. D.
Biochemistry 2002, 41, 14066.
(15) (a) Chenon, M.-T.; Pugmire, R. J.; Grant, D. M.; Panzica, R.
P.; Townsend, L. B. J. Am. Chem. Soc. 1975, 97, 4636.
(b) Chenon, M.-T.; Pugmire, R. J.; Grant, D. M.; Panzica, R.
P.; Townsend, L. B. J. Am. Chem. Soc. 1975, 97, 4627.
13C NMR (75 MHz, CD3OD): d = 15.9 (C-5¢), 20.9 (C-2¢-CH3), 78.3
(C-3¢), 79.8 (C-4¢), 81.3 (C-2¢), 92.9 (C-1¢), 125.8 (C-5), 140.2 (C-
8), 147.2 (C-2), 150.2 (C-4), 159.6 (C-6).
Synthesis 2005, No. 19, 3239–3244 © Thieme Stuttgart · New York