Chiral pool synthesis of calystegine A3 from 2-deoxyglucose via a Brown allylation

Article abstract of DOI:10.1016/j.carres.2011.10.025

Calystegine A₃ is a naturally occurring nortropane iminosugar of which there previously have been three total syntheses. Inspired by our previous work we here report on a fourth approach using 17 steps from 2-deoxy-d-glucose applying a diastereoselective allylation protocol.

Full text of DOI:10.1016/j.carres.2011.10.025

Carbohydrate Research 346 (2011) 2855–2861
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Chiral pool synthesis of calystegine A3 from 2-deoxyglucose via a Brown
allylation
⇑
Tina Secher Rasmussen, Henrik Helligsø Jensen
Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 August 2011
Received in revised form 14 October 2011
Accepted 14 October 2011
Available online 22 October 2011
Calystegine A3 is a naturally occurring nortropane iminosugar of which there previously have been three
total syntheses. Inspired by our previous work we here report on a fourth approach using 17 steps from
2-deoxy-
D
-glucose applying a diastereoselective allylation protocol.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Calystegine
Benzylidene opening
Ring closing metathesis
Staudinger reduction
1. Introduction
hemiaminal OH and the protein.10–13 This binding mode can also
be expected to be in operation for other calystegines.
Calystegines are naturally occurring polyhydroxylated nortro-
panes found in the underground organs and root exudates of plants
belonging to the families Convolvulaceae and Solanaceae, for exam-
ple, Calystegia sepium.1 These compounds are classified into three
groups based on the numbers of hydroxyl groups present on the
bicyclic ring system: those carrying three hydroxyl groups are des-
ignated A, while calystegines containing four or five hydroxyl
groups are designated B and C, respectively. More than 10 different
calystegines have been isolated and some representative examples
are shown in Figure 1, 1–4. A typical feature of calystegines is the
presence of a tertiary hydroxyl group at the bridge head as a part of
a hemiaminal functionality. Due to the structural resemblance to
monosaccharides, many calystegines show significant inhibition
A stereochemically identical yet deoxygenated version of caly-
stegine B2 is calystegine A3 (1), which is also widespread in occur-
rence. It was first isolated from Calystegia sepium in 198814
followed by structural determination in 1990.15,16 There has to
date been three total syntheses of calystegine A3 (1).17–19 The most
recent of these uses a zinc-mediated tandem reaction in combina-
tion with ring-closing metathesis, which allows for the transforma-
tion of an iodo-glycoside into a cycloheptene in two steps.19 Here
we report a new total synthesis of calystegine A3 (1) using a strat-
egy inspired by our recent synthesis of the non-natural analogues
noeurostegine (5)20,21 and uronic-noeurostegine,22 where the
nitrogen atom is introduced as an azide instead of as a carbamate
for easy structure elucidation by avoiding rotamers of several syn-
thetic intermediates.
of glycoside hydrolases, in particular b-glucosidase and both
a-
and b-galactosidases.2–4 Calystegine B2 (2) is the most abundant
of the calystegines and since the structural determination in the
beginning of 1990s it has been a synthetically challenging target
and several elegant total syntheses have been reported.5–8 Recent
crystallographic results have shown that calystegine B2 binds to
Thermotoga maritima of the glycosidase family 1 (TmGH1) in a
‘noeuromycin binding mode’ rather than the opposite ‘1-deoxynoj-
irimycin binding mode’.9 The observed binding mode places the
endocyclic nitrogen atom in the position taken up by C-1 of the
substrate, which will allow for strong interactions between the
2. Results and discussion
Calystegine A3 (1) is deoxygenated in the 4-position and con-
tains two equatorial positioned secondary hydroxyl groups at C2
and C3. This substituent pattern can be found in commercially
available 2-deoxy-D-glucose (6) and hence it was planned to trans-
form this compound into calystegine A3 (1) via a similar route as
applied for noeurostegine (5).20,21 By our earlier results we envis-
aged that calystegine A3 (1) could be obtained in a series of steps
from cycloheptene 8 via azido compound 7. Formation of cyclohep-
tene 8 was to be achieved by a ring-closing metathesis of diene 9,
which in turn was to originate from iodoglucoside 10 through a
⇑
Corresponding author. Tel.: +45 8942 3963.
E-mail address: hhj@chem.au.dk (H.H. Jensen).
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.10.025

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T. S. Rasmussen, H. H. Jensen / Carbohydrate Research 346 (2011) 2855–2861
For the synthesis of 10, 2-deoxyglucose (6) was first trans-
2 OH
HO
HO
1
NH
HO
NH
HO
HO
formed into its methyl glucoside 11 by Fischer glycosylation and
next 4,6-O-benzylidene formation using benzaldehyde dimethyl-
acetal under acidic conditions and reduced pressure (Scheme
2).23,24 Next, the free 3-OH was protected as a benzyl ether in
one-pot to give 12 in a 64% yield over three steps. It was next at-
tempted to regioselectively open the acetal function to liberate
the 6-OH for later substitution with iodide. This, however, proved
troublesome. Opening with DIBAL-H in toluene25,26 gave a regio-
isomeric mixture in favour of the undesired 4-OH product (14) in
contrast to the findings by Tanaka et al. for the regioselectivity in
similar systems undergoing opening with DIBAL-H in toluene.26
Reaction of 12 with borane–THF complex using Cu(OTf)2 was
found to reductively open the acetal with the desired selectively
but was too reactive for this labile 2-deoxy glycoside resulting in
methyl ether 15. This was also the case for LiAlH4/AlCl3. Finally,
borane-trimethylamine complex was tried in combination with
AlCl3. These conditions did provide the free 6-OH compound 13
as the main product, but the yield proved to be low (33%).
HO
HO
HO
5
4
HO
NH
OH
3
7
6
Calystegine A3, 1
Calystegine B2, 2
OH
HO OH
HO
NH
NH
HO
HO
HO
HO
HO
HO
HO
NH
OH
OH
Calystegine C1, 4
Calystegine B4, 3
Noeurostegine, 5
synthetic
Figure 1. Examples of naturally occurring calystegines (1–4) and
analogue 5.
a
zinc-mediated fragmentation and subsequent diastereoselective
allylation of the aldehyde. Methyl 6-iodoglucoside 10 is hence a
key intermediate in our synthesis of calystegine A3 (1), which we
believe could be obtained from 2-deoxy-D-glucose (6) in a series
of steps involving several protecting group manipulations (Scheme
1).
As an alternative approach resembling our initial strategy we
were indeed capable of accessing the needed key iodo-intermedi-
ate 10 for the synthesis of calystegine A3 (1) in five steps starting
PgO
PgO
H
4 steps
PgO
PgO
HO
HO
4 steps
NH
OH
OPg
N3
PgO
8
Calystegine A3, 1
7
OH
I
5 steps
PgO
PgO
2 steps
O
O
PgO
PgO
HO
HO
OPg
OMe
OH
6
10
9
Scheme 1. Retrosynthetic considerations.
OH
O
HO
HO
OH
6
2-deoxy-D-glucose,
MeOH, H+
1) Benzaldehyde dimethyl
acetal, p-TsOH
HO
OH
O
1) Anisaldehyde dimethyl
acetal, p-TsOH
2) BnBr, NaH, DMF
83% (three steps)
Ph
O
PMB
O
O
O
O
O
2) BnBr, NaH, DMF
64% (three steps)
BnO
HO
BnO
OMe
OMe
OMe
12
16
11
DIBAL-H
CH2Cl2
a, b,c or d
HO
O
PMBO
OBn
HO
BnO
BnO
O
BnO
BnO
O
OMe
OMe
HO
17
HO
BnO
OMe
OMe
OH OBn
I2, PPh3,
imidazole,
toluene
13
14
15
13 14 15
a) DIBAL-H, CH2Cl2:
:
:
1:2:0, 36%
13 14 15
0:0:1, 48%
80% (two steps)
b) BH3·THF, Cu(OTf)2:
:
:
I
PMBO
BnO
13 14 15
O
c) LiAlH4, AlCl3, Et2O, CH2Cl2:
:
:
0:0:1, 66%
1:0:0, 33%
13 14 15
:
d) BH3·NMe3, AlCl3, toluene:
:
OMe
18
Scheme 2. Different strategies for formation of protected methyl 2-deoxy-6-hydroxyglucoside.

T. S. Rasmussen, H. H. Jensen / Carbohydrate Research 346 (2011) 2855–2861
2857
from 2-deoxy-
D
-glucose 6 (Scheme 2). Again starting from 2-
tive addition of allyltin reagents29,30 was first attempted, however,
only degradation of the aldehyde was observed (conditions b,
Scheme 3). Then, the Brown allylation was investigated, and this
asymmetric protocol proved to be very efficient.31–36 The Brown
allylation gave hydroxydiene 20 as a diastereoisomeric 1:11 mix-
ture of R- and S-isomers in a 79% yield (conditions c, Scheme 3).
With this satisfactory result we continued with protection of the
secondary alcohol as a benzoyl ester followed by a Hoveyda–Grub-
bs catalysed ring-closing metathesis to give the cycloheptene 22 in
a 76% yield, still as a non-separable mixture of diastereoisomers
(Scheme 3). Oxidation of the double bond by a standard hydrobo-
ration/oxidative workup protocol afforded an isomeric mixture of
secondary alcohols in a 78% yield (Scheme 3). Both regioisomers
23 and 24 were obtained as a single isomer which corresponds
to previous observations in the noeurostegine (5) synthesis.20
The regioisomeric ratio was 2:1 in favour of the desired product
24 in accordance with Madsen and co-workers observation in a
similar system.19
deoxy- -glucose (6) via the methyl glucoside (11) we formed the
D
4,6-p-methoxybenzylidene acetal by reaction with p-methoxy-
benzaldehyde dimethylacetal in the presence of PTSA followed
by benzylation of the free 3-OH in one pot afforded the protected
2-deoxyglucoside 16 in 83% yield over three steps. Next, we found
it to be possible to open the 4,6-acetal of 16 using DIBAL-H in tol-
uene with complete regioselectivity, affording compound 17 bear-
ing a free 6-OH. Opening of the p-methoxybenzylidene acetal was
also attempted with DIBAL-H in THF, however, no reaction was ob-
served under these conditions. This reaction was followed by
iodination to give 18 in an 80% yield over two steps (Scheme 2).
Zinc-mediated fragmentation of iodide 18 under sonication in
THF–H2O as described by Madsen and co-workers27 resulted in
clean conversion into aldehyde 19, which was used directly in
the following Barbier reaction28 without purification. This resulted
in a non-separable diastereoisomeric 2:3 mixture of homoallylic
alcohol 20R/20S in an 80% yield (conditions a, Scheme 3). The ste-
reochemistry at the new stereogenic centre was established after
the ring-closing metathesis reaction. As a consequence of the reac-
tion outcome and the fact that the isomers could not be separated
we investigated an asymmetric allylation as an alternative. Two
asymmetric allylation protocols were investigated. Diastereoselec-
The secondary alcohol of 24 was protected as a silyl ether (25)
with triisopropylsilyl triflate in dichloromethane followed by ben-
zoyl ester removal by Zemplén deacylation37 to give alcohol 26 in a
94% yield over two steps (Scheme 4). The free secondary alcohol 27
was then substituted for azide under Mitsunobu-type conditions38
PMBO
PMBO
I
Zn
O
a, b or c
O
PMBO
BnO
THF/H2O
BnO
BnO
OH
OMe
19
18
20
BzCl, DMAP, Pyr
Grubbs-Hoveyda, CH2Cl2
PMBO
BnO
PMBO
BnO
76% (two steps)
OBz
OBz
21
22
1) BH3·THF
HO
OH
2) NaOH, H2O2
78%
PMBO
PMBO
+
BnO
OBz
BnO
OBz
:
2
23
1
24
Scheme 3. Synthesis of cycloheptane 23 and 24 from iodoglucoside 18. Reagents and conditions for attempted allylations: (a) Allyl-Br, In(s), THF/H2O, 80%, dr 3:2; (b) (S)-
BINOL, Ti(OiPr)4, allyl-Sn(Bu)3, CH2Cl2, no product; (c) 1) (ꢀ)-Ipc-allylborane, Et2O, then NaBO3ꢁ4H2O, THF/H2O, 79%, dr 11:1.
HO
TIPSO
PMBO
TIPSO
PMBO
TIPSO
PMBO
TIPS-OTf,
DPPA, DIAD,
PPh3
PMBO
BnO
CH3ONa
2,4,6-collidine
CH2Cl2
MeOH,
94%
THF, 80%
BnO
OBz
OBz
BnO
BnO
OH
N3
(two steps)
24
25
27
26
TBAF,
THF
89%
HO
O
Na(s)/NH3(l)
DMP
PMBO
PPh3
PMBO
HO
HO
BnO
NH
OH
PMBO
NH
OH
CH2Cl2, rt
95%
THF
47%
THF/H2O
83%
BnO
N3
BnO
N3
30
1
29
28
Scheme 4. Synthesis of calystegine A3 from intermediate 24.

2858
T. S. Rasmussen, H. H. Jensen / Carbohydrate Research 346 (2011) 2855–2861
to afford an easy separable mixture of azides 27 in an 80% yield
(Scheme 4). The desired R-configured azide 27R was then treated
with TBAF in THF to give secondary alcohol 28 in good yield. Sub-
sequent oxidation of alcohol 28 by Dess–Martin periodinane39
(DMP) afforded azido ketone 29 in a 95% yield (Scheme 4). Based
on our previous experience from the synthesis of the calystegine
B2 analogue, noeurostegine (5),20 we chose to conduct the cyclisa-
tion and deprotection in two separate steps. Accordingly, azido ke-
tone 29 was treated with triphenyl phosphine under Staudinger
conditions40 to afford the spontaneously cyclized product 30 in
an 83% yield. A hemiaminal 13C chemical shift of 93.4 ppm instead
of a ketone resonance at around 209 ppm indicated the presence of
the bicyclic compound. Catalytic hydrogenation over either Pearl-
man’s catalyst or palladium on charcoal was not successful, even
under acidic conditions (TFA or hydrochloride acid). Deprotection
of the two ether protection groups was instead achieved via Birch
reduction which yielded the natural product 1 in moderate yield
(Scheme 4).41–47 Calystegine A3 was separated from ammonium
chloride by an acidic ion-exchange column and the optical rotation
and spectroscopic data were in agreement with the literature
data.2,15,16
4.2. Methyl 3-O-benzyl-2-deoxy-4,6-O-(p-methoxybenzylidene)-
/b- -glucopyranoside (16)
a
D
2-Deoxy-D-glucose (6) (4.77 g, 0.05 mol) was dissolved in dry
MeOH (75 mL) under an atmosphere of nitrogen. Amberlite IR-
120 (H+) ion exchange resin (10 mL) was added and the reaction
mixture was stirred at 30 °C for 3 days. The reaction mixture was
filtered and the ion exchange resin was washed with MeOH
(3 ꢂ 50 mL) and concentrated. The resulting product 11 (5.58 g)
was concentrated twice from toluene prior to dissolution in dry
DMF (80 mL). Anisaldehyde dimethyl acetal (7.5 mL, 0.04 mol,
1.4 equiv) and enough of a catalytic amount of p-TsOH to make
an acidic solution (pH-paper) were added and the reaction mixture
was stirred under reduced pressure (200 mbar) at 40 °C for 1 h. The
reaction mixture was cooled to 0 °C and sodium hydride (60%,
6.27 g, 0.16 mol, 5 equiv) was added in small portions. After stir-
ring for 10 min at 0 °C benzyl bromide (7.5 mL, 0.06 mol, 2 equiv)
was added. The reaction mixture was warmed to rt and stirred
for 17 h. To obtain reaction completion, the reaction mixture again
was cooled to 0 °C and further portions of sodium hydride (2.5 g,
0.06 mol, 2 equiv) and benzyl bromide (8.0 mL, 0.07 mol, 2.2 equiv)
were added. The reaction mixture was then warmed to rt and stir-
red for three another hours after which TLC analysis indicated full
conversion of starting material. The reaction was quenched by
dropwise addition of MeOH (60 mL) and then diluted with EtOAc
(250 mL). The organic phase was washed with H2O (3 ꢂ 250 mL)
and brine (3 ꢂ 250 mL), dried over MgSO4, filtered and concen-
trated. The resulting residue was purified by flash column chroma-
tography (pentane/EtOAc 20:1?10:1?5:1) to give the desired
product 16 (9.32 g, 83% (three steps) colourless oil) as a 7:1 (deter-
3. Conclusion
The naturally occurring compound calystegine A3 has been suc-
cessfully synthesised in 17 steps from 2-deoxy-D-glucose with
nitrogen introduced as an azide allowing for well resolved NMR
spectra and thereby easy structural determination. Brown allyla-
tion of an intermediate a-unsubstituted aldehyde proceeded with
in good diastereoisomeric control (11:1) and formation of a signif-
icant amount of the unusable diastereoisomer was thereby
avoided.
mined by 13C NMR) mixture of
a
/b anomers. 1H NMR (400 MHz,
CDCl3): dH (ppm) -anomer: 7.44–7.27 (m, 7H, ArH), 6.90 (m, 2H,
a
PhOCH3), 5.58 (s, 1H, CHPhOCH3), 4.82 (d, 1H, J 12.0 Hz, CH2Ph),
4.80 (br s, 1H, H1), 4.67 (d, 1H, J 12.0 Hz, CH2Ph), 4.24 (m, 1H,
H6a), 4.00 (m, 1H, H3), 3.82 (s, 3H, CH3OPh), 3.79–3.73 (m, 2H,
H6b,H5), 3.67 (m, 1H, H4), 3.33 (s, 3H, OCH3), 2.26 (m, 1H, H2ax),
1.79 (ddd, 1H, J 4.0 Hz, J 11.2 Hz, J 13.2 Hz, H2eq). NMR was in
accordance with previous reported data.48
4. Experimental section
4.1. General methods
All reagents except otherwise stated were used as purchased
without further purification. Zinc was activated as previously de-
scribed.20 Oven dried glassware (ca. 120 °C) was used for reactions
carried out under nitrogen or argon atmosphere. Solvents were
dried using MB-SPS Solvent Purification System. Flash chromatog-
raphy was performed with Merck Silica 60 (230–400 mesh) as the
stationary phase and TLC was performed on silica-coated alumin-
ium plates (Merck 60 F254). TLC plates were first observed in
UV-light and then visualised with ceric sulphate/ammonium
molybdate in 10% H2SO4 stain or KMnO4-stain. 1H NMR
(400 MHz) and 13C NMR (100 MHz) were recorded at a Varian Mer-
cury 400 spectrometer. CDCl3 (d 7.26 ppm (CHCl3) for proton and d
77.16 ppm for carbon resonances) and D2O (d 4.79 ppm for proton)
were used as internal references. Spectra were assigned based on
gCOSY, gHMQC, and DEPT-135 experiments. MS spectra were re-
corded at a Micromass LC-TOF instrument by using electrospray
ionization (ESI). High resolution spectra were recorded with either
4.3. Methyl 3-O-benzyl-2,6-dideoxy-6-iodo-4-O-p-
methoxybenzyl-a/b-D-glucopyranoside (18)
DIBAL-H (1 M in toluene, 40 mL, 40.0 mmol, 3 equiv) was added
over 30 min to a solution of 16 (5.18 g, 13.4 mmol) in dry CH2Cl2
(170 mL) at 0 °C. The reaction was quenched, after stirring for
45 min, by dropwise addition of aq HCl (1 M, 100 mL). The organic
phase was washed with a satd aq solution of NaHCO3 (100 mL),
brine (3 ꢂ 200 mL), dried over MgSO4, filtered and concentrated.
The resulting alcohol product 17 (5.20 g) (the 4-OH isomer could
not be detected by crude 13C NMR) was dissolved in dry toluene
(100 mL) and PPh3 (8.32 g, 31.7 mmol, 2.5 equiv), I2 (3.55 g,
14.0 mmol, 1.1 equiv) and imidazole (1.74 g, 25.6 mmol, 2.0 equiv)
were added. The reaction mixture was heated at reflux for 1.5 h
then cooled to rt and added a sated aq solution of Na2S2O3
(140 mL). The organic phase was washed with brine
(3 ꢂ 200 mL), dried over MgSO4, filtered and concentrated. The
crude product was purified by flash column chromatography (pen-
tane/EtOAc 20:1?15:1) to give the desired product 18 (5.33 g, 80%
of the following compounds as internal standard: (Boc-L-alanine:
C8H15NO4Na: 212.0899; BzGlyPheOMe: C19H20N2O4Na: 363.1321;
BocSer(OBn)SerLeuOMe: C25H39N3O8Na: 532.2635; erythromycin:
C
37H67NO13Na: 756.4510) Masses of standards and analytes are
(two steps)) as a 7:1 mixture of
a/b anomers. a anomer: Rf (pen-
tane/EtOAc 10:1) 0.48. 1H NMR (400 MHz, CDCl3): dH (ppm)
7.37–7.23 (m, 7H, ArH), 6.87 (m, 2H, PhOCH3), 4.92 (d, 1H, J
10.4 Hz, CH2Ph), 4.82 (d, 1H, J 3.6 Hz, H1), 4.67 (d, 1H, J 11.6 Hz,
CH2Ph), 4.65 (d, 1H, J 10.4 Hz, CH2Ph), 4.61 (d, 1H, J 11.6 Hz,
CH2Ph), 3.98 (m, 1H, H3), 3.81 (s, 3H, CH3OPh), 3.52 (m, 1H,
H6a), 3.43–3.29 (m, 6H, H4, H5, H6b, OCH3), 2.29 (m, 1H, H2ax),
1.69 (dt, 1H, J 3.6 Hz, J 11.6 Hz, H2 eq). 13C NMR (100 MHz, CDCl3):
calculated and reported in Daltons for un-charged species. Optical
rotation was measured on a PE-241 polarimeter and reported in
units of degꢁcm2/g. Concentrations are reported in g/100 mL. Soni-
cation was conducted by the use of a Branson 1510 sonic bath.
Microwave experiments were carried out on a Biotage Initiator
(Biotage, Sweden). Reaction times listed refer to ‘hold time’ at
the specified temperature.

T. S. Rasmussen, H. H. Jensen / Carbohydrate Research 346 (2011) 2855–2861
2859
dC (ppm) 159.3, 138.5, 130.4, 129.6, 128.4, 127.6, 113.8 (ArC), 98.4
(C1), 81.8, 77.1, 74.9, 71.6, 69.9, 55.2, 54.9, 35.4, 8.6 (C6).
HRMS(ES+): calcd for C22H27I NaO5: 521.0801, found 521.0804.
10 min. The mixture was diluted with EtOAc (120 mL) and the
organic phase washed with 1 M HCl (3 ꢂ 100 mL), a satd aq solu-
tion of NaHCO3 (3 ꢂ 100 mL), brine (2 ꢂ 100 mL), dried over
MgSO4 and concentrated. The resulting product 21 (1.38 g) and
Hoveyda–Grubbs 2nd generation catalyst (35 mg, 0.056 mmol,
0.02 equiv) were dissolved in dry CH2Cl2 (15 mL) in a sealed micro-
wave vial. The reaction mixture was heated by microwave irradia-
tion for 3 min (80 °C) after which the formed ethylene gas was
released; the microwave irradiation was then continued for
10 min. Then more Hoveyda–Grubbs 2nd generation catalyst
(10 mg, 0.016 mmol, 0.006 equiv) was added and microwave irra-
diation was resumed for another 10 min. The solvent was removed
under reduced pressure and the remaining residue was purified by
column chromatography (pentane/EtOAc 20:1) to give the desired
cycloheptene 24 as a 1:11 diastereoisomeric mixture (1.10 g, 84 %
(two steps)). Rf (pentane/EtOAc 10:1) 0.47. 1H NMR (400 MHz,
CDCl3): dH (ppm) 8.00 (m, 2H, ArH), 7.55 (m, 1H, ArH), 7.43 (m,
2H, ArH), 7.34–7.25 (m, 7H, ArH), 6.87 (m, 2H, PhOCH3), 5.86 (m,
2H, H1, H2), 5.35 (m, 1H, H6), 4.72 (d, 1H, J 11.6 Hz, CH2Ph), 4.65
(d, 1 H, J 11.6 Hz, CH2Ph), 4.62 (d, 1H, J 11.2 Hz, CH2Ph), 4.52 (d,
1H, J 11.2 Hz, CH2Ph), 4.17 (dd, 1H, J 3.6 Hz, J 7.2 Hz, H3), 3.88
(dt, 1H, J 7.2 Hz, J 2.8 Hz, H4), 3.81 (s, 3H, CH3OPh), 2.66 (m, 1H,
H7), 2.52 (m, 1H, H70), 2.40 (ddd, 1H, J 2.8 Hz, J 8.8 Hz, J 14.4 Hz,
H5), 2.26 (ddd, 1H, J 3.2 Hz, J 7.2 Hz, J 14.4 Hz, H50). 13C NMR
(100 MHz, CDCl3): dC (ppm) 165.8 (CO), 159.3, 138.7 (ArC), 133.0
(C1/C2), 132.3, 130.8–127.6 (ArC, C2/C1), 113.9 (ArC), 78.7 (C3),
75.9 (C4), 71.8 (CH2Ph), 71.4 (CH2Ph), 69.2 (C6), 55.4 (CH3OPh),
36.2 (C7), 33.1 (C5). HRMS(ES+): calcd for C29H30NaO5: 481.1991,
found 481.1995.
4.4. (3R,4R)-3-O-Benzyloxy-4-O-p-methoxybenzyloxy-hex-5-
enal (19)
To a solution of iodide 18 (1.80 g, 3.62 mmol) in THF (70 mL)
was added pre-activated Zn dust20 (2.60 g, 39.8 mmol, 11 equiv)
and H2O (10 mL). The resulting suspension was sonicated at
40 °C until TLC-analysis showed full conversion (2.5 h). The reac-
tion mixture was then diluted with Et2O (150 mL) and H2O
(60 mL) and the resulting mixture filtered through a pad of Celite
and the organic phase washed with H2O (100 mL) and brine
(100 mL), and dried over Na2SO4 and concentrated. The isolated
aldehyde 19 (1.26 g) was used directly in the next reaction without
further purification. Rf (pentane/EtOAc 10:1) 0.31. 1H NMR
(400 MHz, CDCl3): dH (ppm) 9.70 (s, 1H, CHO), 7.35–7.21 (m, 7H,
ArH), 6.87 (m, 2H, PhOCH3), 5.83 (ddd, 1H, J4,5 6.8 Hz, Jcis 10.4 Hz,
Jtrans 17.2 Hz, H5), 5.36 (m, 2H, H6a, H6b), 4.69 (d, 1H, J 11.2 Hz,
CH2Ph), 4.62 (d, 1H, J 11.6 Hz, CH2Ph), 4.57 (d, 1H, J 11.2 Hz,
CH2Ph), 4.32 (d, 1H, J 11.6 Hz, CH2Ph), 4.08 (m, 1H, H3), 3.97 (t,
1H, J 6.8 Hz, H4), 3.81 (s, 3H, CH3OPh), 2.66 (ddd, 1H, J1,2a 1.6 Hz,
J2a,3 4.4 Hz, Jgem 16.8 Hz, H2a), 2.58 (ddd, 1H, J1,2b 2.4 Hz, J2b,3
8.4 Hz, Jgem 16.8 Hz, H2b).
4.5. (3R,4R,6R/S)-4-O-Benzyloxy-6-hydroxy-3-O-p-
methoxybenzyloxy-nona-1,8-diene (20R/S)
To a stirred solution of the intermediate aldehyde 19 (1.26 g,
3.70 mmol) in dry Et2O (50 mL) at ꢀ100 °C a solution of (ꢀ)-
Ipc-allylborane in pentane (1 M, 10 mL, 10.0 mmol, 2.7 equiv)
slowly cannulated at ꢀ78 °C into the cooled Et2O solution. The
reaction mixture was stirred at ꢀ100 °C for 2 h and then
quenched by dropwise addition of MeOH (6 mL). The mixture
was warmed to rt and then concentrated. The resulting residue
was dissolved in THF/H2O (1:1, 40 mL) and NaBO3ꢁH2O (1.43 g,
9.26 mmol, 2.5 equiv) was added and the reaction mixture was
stirred at rt for 17 h. The mixture was diluted with brine
(100 mL) and the aqueous phase extracted with Et2O
(3 ꢂ 100 mL). The combined organic phases were dried over
MgSO4 and concentrated before the crude product was purified
by column chromatography (pentane/EtOAc 25:1?20:1?10:1)
to give the desired product 20 (1.09 g, 79% (two steps)) as a
1:11 non-separable mixture of R- and S-diastereoisomers. Rf (pen-
tane/EtOAc 7:1) 0.27. S-isomer: 1H NMR (400 MHz, CDCl3): dH
(ppm) 7.33–7.24 (m, 7H, ArH), 6.86 (m, 2H, PhOCH3), 5.70 (m,
2H, H2, H8), 5.32 (m, 2H, H1/H9), 5.08 (m, 2H, H9/H1), 4.77 (d,
1H, J 11.2 Hz, CH2Ph), 4.59 (d, 1H, J 11.2 Hz, CH2Ph), 4.58 (d,
1H, J 11.6 Hz, CH2Ph), 4.35 (d, 1H, J 11.6 Hz, CH2Ph), 3.96 (m,
1H, H3) 3.84–3.77 (m, 5H, H4, H6, CH3OPh) 2.18 (m, 2H, H7)
1.62 (dd, 2 H, J 5.6 Hz, J 6.4 Hz, H5). 13C NMR (100 MHz, CDCl3):
dC (ppm) 159.2, 138.6 (ArC), 135.1, 135.0 (C2,C8) 130.4, 129.4,
128.5, 128.4, 128.1, 127.7 (ArC) 119.0, 117.6 (C1,C9) 113.8
(ArC), 82.1 (C3) 78.4 (C4/C6) 73.5 (CH2Ph) 70.3 (CH2Ph) 67.7
(C6/C4) 55.2 (CH3OPh) 42.4 (C7) 37.5(C5). HRMS(ES+): calcd for
4.7. (1R/S,3R,4R,6R/S)-1-O-Benzoyloxy-3-O-benzyloxy-4-O-p-
methoxybenzyloxy-cycloheptane 6-ol (23) and (1R/S,3R,4R,5R)-
1-O-benzoyloxy-3-O-benzyloxy-4-O-p-methoxybenzyloxy-
cycloheptane-5-ol (24)
BH3ꢁTHF complex (1 M solution in THF, 4.8 mL, 4.80 mmol,
2 equiv) was added in a dropwise fashion to a stirred solution of
22 (1.10 g, 2.40 mmol) in dry THF (25 mL) at 0 °C. After stirring
for 2 h at 0 °C, NaOH (2 M, 5 mL) and aq H2O2 (35%, 10 mL) was
added. The reaction mixture was allowed to reach rt and stirred
for additional 2 h before diluted with Et2O (100 mL). The organic
phase was washed with H2O (2 ꢂ 100 mL), brine (3 ꢂ 100 mL),
dried over MgSO4 and concentrated. The crude product was puri-
fied by column chromatography (pentane/EtOAc 4:1) to give
regioisomers 24 and 25 (0.96 g, 84% (overall yield)) as a 2:1 mix-
ture which were easily separated.
4.8. (1R/S,3R,4R,6R/S)-1-O-Benzoyloxy-3-O-benzyloxy-4-O-p-
methoxybenzyloxy-cycloheptane-6-ol (23)
Colourless oil (0.33 g, 29%). Rf (pentane/EtOAc 2:1) 0.29. 1H
NMR (400 MHz, CDCl3): dH (ppm) 8.03 (m, 2H, ArH), 7.55 (m, 1H,
ArH), 7.42 (m, 2H, ArH), 7.34–7.22 (m, 7H, ArH), 6.86 (m, 2H,
PhOCH3), 5.50 (m, 1H, H1), 4.68 (d, 1H, J 11.6 Hz, CH2Ph), 4.57 (d,
1H, J 11.2 Hz, CH2Ph), 4.47 (m, 2H, CH2Ph), 4.24 (m, 1H, H6), 3.85
(m, 2H, H3, H4), 3.80 (s, 3H, CH3OPh), 2.22 (m, 3H, H2, H5, H7),
2.14 (m, 3H, H20, H50, H70). 13C NMR (100 MHz, CDCl3): dC (ppm)
165.8 (CO), 159.3, 138.2, 133.0 (ArC), 130.7–127.7 (ArC) 113.9
(ArC), 77.6, 77.0, 71.5, 71.3, 68.5, 64.3, 55.4 (CH3OPh), 43.9, 38.7,
33.3. HRMS(ES+): calcd for C29H32NaO6: 499.2097, found 499.2101.
C24H30NaO4: 405.2042, found 405.2039.
4.6. (3R,4R,6R/S)-6-O-benzoyloxy-4-O-benzyloxy-3-O-p-
methoxybenzyloxycycloheptene (22)
To a stirred solution of hydroxydiene 20 (1.10 g, 2.87 mmol) in
dry pyridine (40 mL) were added BzCl (0.7 mL, 6.04 mmol, 2 equiv)
and a catalytic amount of DMAP (35 mg, 0.29 mmol, 0.1 equiv). The
reaction mixture was stirred at rt for 16 h and then quenched by
dropwise addition of H2O (50 mL) and continuous stirring for
4.9. (1R/S,3R,4R,5R)-1-O-Benzoyloxy-3-O-benzyloxy-4-O-p-
methoxybenzyloxy-cycloheptane-5-ol (24)
Colourless oil (0.63 g, 55%). Rf (pentane/EtOAc 4:1) 0.17. 1H
NMR (400 MHz, CDCl3): dH (ppm) 8.03 (m, 2H, ArH), 7.57 (m, 1H,

2860
T. S. Rasmussen, H. H. Jensen / Carbohydrate Research 346 (2011) 2855–2861
ArH), 7.47–7.21 (m, 9H, ArH), 6.88 (m, 2H, PhOCH3), 5.36 (m, 1H,
H1), 4.78 (d, 1H, J 11.2 Hz, CH2Ph), 4.71 (d, 1H, J 11.2 Hz, CH2Ph),
4.55 (d, 1H, J 11.2 Hz, CH2Ph), 4.50 (d, 1H, J 11.2 Hz, CH2Ph), 3.87
(m, 1H, H3), 3.81 (s, 3H, CH3OPh), 3.72 (m, 1H, H5), 3.48 (dd, 1H,
J 7.6 Hz, J 4.8 Hz, H4), 2.65 (br s, 1H, OH), 2.34 (ddd, 1H, J 2.4 Hz,
J 7.2 Hz, J 14.8 Hz, H2), 2.24 (m, 1H, H7), 2.10–1.97 (m, 2H, H20,
H6), 1.70 (m, 2H, H60, H70). 13C NMR (100 MHz, CDCl3): dC (ppm)
165.9 (CO), 159.5, 138.1, 133.0 (ArC), 130.7–127.9 (ArC), 114.1
(ArC), 87.5 (C4), 77.1 (C3), 73.3 (CH2Ph), 73.0 (C5), 71.2 (CH2Ph),
70.9 (C1), 55.4 (CH3OPh), 33.3 (C2), 30.1, 28.0 (C6,C7). HRMS(ES+):
calcd for C29H32NaO6: 499.2097, found 499.2094.
2.4 Hz, H1), 3.80 (s, 3H, CH3OPh), 3.64 (dd, 1H, J 2.0 Hz, J 6.0 Hz,
H2), 3.52 (ddd, 1H, J 1.6 Hz, J 6.4 Hz, J 10.8 Hz, H3), 3.27 (ddt, 1H,
J 2.4 Hz, J 4.4 Hz, J 11.2 Hz, H5), 2.35 (m, 1H, H4), 2.05 (m, 2H,
H40,H6), 1.87 (m, 1H, H7), 1.77 (m, 1H, H60), 1.68 (m, 1H, H70),
1.09 (s, 21H, CHCH3, CHCH3). 13C NMR (100 MHz, CDCl3): dC
(ppm) 159.3, 150.0, 149.9, 138.5, 130.8, 130.2, 129.6, 128.5,
127.9, 127.7, 126.2, 120.4, 113.8 (ArC), 87.0 (C2) 82.0 (C3), 72.7
(CH2Ph), 71.6 (CH2Ph), 70.5 (C1) 60.3 (C5) 55.4 (CH3OPh), 34.6
(C4), 26.7, 25.9 (C6,C7), 18.2, 12.4 (CHCH3, CHCH3). HRMS(ES+):
calcd for C31H47N3NaO4Si: 576.3234, found 576.3234.
4.13. (1R,2S,3R,5S)-5-Azido-3-O-benzyloxy-2-O-p-
methoxybenzyloxy-1-O-triisopropylsilyl-cycloheptane (27S)
4.10. (3R,4S,5R)-3-O-Benzyloxy-4-O-p-methoxybenzyloxy-5-O-
triisopropylsilyl-cycloheptan-1-ol (26)
Colourless oil (66 mg, 10%). Rf (pentane/EtOAc 80:1) 0.43.
TIPS-OTf (0.60 mL, 2.22 mmol, 1.7 equiv) and 2,4,6-collidine
(0.38 mL, 2.88 mmol, 2.2 equiv) were added to a solution of 24
(0.63 g, 1.31 mmol) in dry CH2Cl2 (10 mL). The reaction mixture
was stirred at rt for 90 min and then quenched by addition of satd
aq solution of NaHCO3 (80 mL). The aqueous phase was extracted
with CH2Cl2 (3 ꢂ 70 mL) and the combined organic phases were
washed with aq HCl (1 M, 50 mL), satd aq NaHCO3 (2 ꢂ 50 mL),
brine (2 ꢂ 50 mL), dried over MgSO4 and concentrated. The result-
ing product 25 (0.98 g, 1.55 mmol) was used directly in the next
reaction without further purification. Sodium (105 mg, 4.57 mmol,
2.9 equiv) was dissolved in dry MeOH (12 mL) and the resulting
solution added to the crude product 25 (0.98 g, 1.55 mmol) under
an atmosphere of nitrogen. The reaction mixture was stirred over-
night before being diluted with EtOAc (80 mL) and the organic
phase washed with water (3 ꢂ 80 mL), dried over MgSO4 and con-
centrated. The crude product was purified by flash column chro-
matography (pentane/EtOAc 7:1?5:1) to give the desired
product 26 (0.64 g, 92%) as a colourless oil. Rf (pentane/EtOAc
5:1) 0.33. 1H NMR (400 MHz, CDCl3): dH (ppm) 7.36–7.23 (m, 7H,
ArH), 6.85 (m, 2H, PhOCH3), 4.58 (m, 4H, CH2Ph), 4.10 (m, 2H,
H1, H5), 3.93 (m, 1H, H3), 3.80 (s, 3H, CH3OPh), 3.63 (m, 1H, H4),
2.17 (m, 2H, H2, H6/H7), 1.93 (m, 2H, H2, H7/H6), 1.77 (m, 1H,
H6/H7) 1.60 (br s, 1H, OH), 1.51 (m, 1H, H2/H6/H7), 1.08 (s, 21
H, CHCH3, CHCH3. 13C NMR (100 MHz, CDCl3): dC (ppm) 159.2,
139.0, 131.0, 129.4, 128.4, 127.8, 127.5, 113.8 (ArC), 87.1 (C4),
77.6 (C3), 73.5 (C1/C5), 72.6 (CH2Ph), 71.3 (CH2Ph) 67.2 (C5/C1)
55.4 (CH3OPh) 36.3 (C2), 31.7, 26.0 (C6,C7), 18.3 (CHCH3), 12.5
(CHCH3). HRMS(ES+): calcd for C31H48NaO5Si: 551.3169, found
551.3170.
4.14. (1R,2R,3R,5R)-5-Azido-3-O-benzyloxy-2-O-p-
methoxybenzyloxy-cycloheptan-1-ol (28)
TBAF (1 M in THF, 2.0 mL, 2.0 mmol, 5 equiv) was added to a
stirred solution of 27R (0.22 g, 0.40 mmol) in dry THF (6 mL).
The reaction mixture was stirred for 2 h before being quenched
by addition of satd aq NH4Cl (40 mL). The aqueous phase was
extracted with EtOAc (3 ꢂ 40 mL) and the combined organic
phases were washed with brine (3 ꢂ 60 mL), dried over MgSO4
and concentrated. The resulting product was purified by flash
column chromatography (pentane/EtOAc 4:1) to give the desired
product 28 (0.14 g, 89%) as a colourless oil. ½a D20
ꢀ22 (c 1.0,
ꢃ
CHCl3). Rf (pentane/EtOAc 5:1) 0.15. 1H NMR (400 MHz, CDCl3):
dH (ppm) 7.37–7.21 (m, 7H, ArH), 6.88 (m, 2H, PhOCH3), 4.83
(d, 1H, J 12.0 Hz, CH2Ph), 4.73 (d, 1H, J 12.0 Hz, CH2Ph), 4.60
(d, 1H, J 12.0 Hz, CH2Ph), 4.57 (d, 1H, J 12.0 Hz, CH2Ph), 3.81
(s, 3H, CH3OPh), 3.60 (m, 3H, H1, H3, H5), 3.47 (m, 1H, H2),
2.73 (br s, 1H, OH), 2.19 (ddd, 1H, J 4.0 Hz, J 4.0 Hz, J 16.0 Hz,
H4), 1.97 (m, 1H, H40), 1.85 (m, 4H, H6, H60, H7, H70). 13C
NMR (100 MHz, CDCl3): dC (ppm) 159.5, 138.0, 130.5, 129.6,
128.5, 127.9, 114.1 (ArC), 86.8 (C2) 79.6 (C3), 74.3 (CH2Ph),
72.3 (CH2Ph), 71.3 (C1/C5), 58.0 (C5/C1), 55.3 (CH3OPh), 34.0
(C4), 27.6, 26.9 (C6,C7). HRMS(ES+): calcd for C22H27N3NaO4:
420.1899, found 420.1914.
4.15. (2S,3R,5R)-5-Azido-3-O-benzyloxy-2-O-p-
methoxybenzyloxy-cycloheptanone (29)
Dess–Martin periodinane (0.24 g, 0.56 mmol, 1.6 equiv) was
added to a stirred solution of 28 (0.14 g, 0.36 mmol) in CH2Cl2
(5 mL). The reaction mixture was stirred for 1 h and then diluted
with Et2O (20 mL) after which stirring was continued for 30 min.
The resulting mixture was washed with a satd aq solution of
Na2S2O3 (3 ꢂ 25 mL), brine (2 ꢂ 25 mL), dried over MgSO4 and
concentrated. The crude product was purified by flash column
chromatography (pentane/EtOAc 10:1) to give product 29
4.11. (1R,2S,3R,5R/S)-5-Azido-3-O-benzyloxy-2-O-p-
methoxybenzyloxy-1-O-triisopropylsilyl-cycloheptane (27)
To a cooled (0 °C) and stirred solution of alcohol 26 (0.64 g,
1.21 mmol) in dry THF (20 mL) were consecutively added PPh3
(0.95 g, 3.61 mmol, 3 equiv), DPPA (0.69 mL, 3.20 mmol, 2.6 equiv)
and DIAD (0.66 mL, 3.18 mol, 2.6 equiv) in a dropwise fashion. The
reaction mixture was allowed to reach rt and then stirred for 2 h.
The reaction mixture was concentrated and the resulting residue
was purified by flash column chromatography (pentane/EtOAc
80:1) to give the product 27 (0.54 g, 80%) as a 1:8 separable mix-
ture of S- and R-diastereoisomers.
(0.13 g, 95%) as a colourless oil. ½a D20
ꢀ11 (c 1.0, CHCl3). Rf (pen-
ꢃ
tane/EtOAc 7:1) 0.39. 1H NMR (400 MHz, CDCl3): dH (ppm) 7.34–
7.21 (m, 7H, ArH), 6.85 (m, 2H, PhOCH3), 4.59 (s, 2H, CH2Ph),
4.50 (d, 1H, J 11.6 Hz, CH2Ph), 4.37 (d, 1H, J 11.6 Hz, CH2Ph),
4.07 (d, 1H, J 6.0 Hz, H2), 3.79 (s, 3H, CH3OPh), 3.74 (m, 2H,
H3, H5), 2.58 (ddd, 1H, J 4.0 Hz, J 10.8 Hz, J 14.8 Hz, H7), 2.47
(ddd, 1H, J 4.0 Hz, J 7.6 Hz, J 14.8 Hz, H70), 2.18 (m, 2H, H4,
H6), 1.95 (m, 1H, H40), 1.85 (m, 1H, H60). 13C NMR (100 MHz,
CDCl3): dC (ppm) 208.8 (CO), 159.6, 137.9, 129.9, 128.4, 127.8,
127.7, 113.9 (ArC), 87.4 (C2), 77.0 (C3/C5), 72.3 (CH2Ph), 72.1
(CH2Ph), 58.5 (C5/C3), 55.3 (CH3OPh), 36.4 (C7), 35.2 (C4), 29.3
(C6). HRMS(ES+): calcd for C22H25N3NaO4: 418.1743, found
418.1748.
4.12. (1R, 2S, 3R, 5R)-5-azido-3-O-benzyloxy-2-O-p-
methoxybenzyloxy-1-O-triisopropylsilyl-cycloheptane (27R)
Colourless oil (0.47 g, 71%). 0.23. ½a D20
ꢀ32 (c 1.0, CHCl3). Rf
ꢃ
(pentane/EtOAc 80:1) 1H NMR (400 MHz, CDCl3): dH (ppm) 7.35–
7.22 (m, 7H, ArH), 6.86 (m, 2H, PhOCH3), 4.65 (d, 1H, J 11.6 Hz,
CH2Ph), 4.63 (d, 1H, J 10.8 Hz, CH2Ph), 4.58 (d, 1H, J 10.8 Hz,
CH2Ph), 4.55 (d, 1H, J 10.8 Hz, CH2Ph), 4.17 (dd, 1H, J 7.2 Hz, J

T. S. Rasmussen, H. H. Jensen / Carbohydrate Research 346 (2011) 2855–2861
2861
4.16. (1R,2S,3R,5R)-3-O-Benzyloxy-2-O-p-methoxybenzyloxy-8-
azabicyclo[3.2.1]octane-1-ol (30)
can be found, in the online version, at doi:10.1016/
j.carres.2011.10.025.
PPh3 (0.39 g, 1.49 mmol, 2 equiv) was added to a stirred solu-
tion of ketone 29 (0.29 g, 0.74 mmol) in THF (10 mL) and H2O
(1 mL). The reaction mixture was stirred at 40 °C for 2 h during
which N2 evolution was observed. The reaction mixture was con-
centrated and the crude product purified by flash column chroma-
tography (EtOAc/MeOH 20:1) to give the desired product 30
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7.30–7.24 (m, 7H, ArH), 6.82 (m, 2H, PhOCH3), 4.89 (br s, 2H, NH,
OH), 4.87 (d, 1H, J 10.8 Hz, CH2Ph), 4.69 (d, 1H, J 10.8 Hz, CH2Ph),
4.59 (d, 1H, J 11.6 Hz, CH2Ph), 4.54 (d, 1H, J 11.6 Hz, CH2Ph), 3.74
(s, 3H, CH3OPh), 3.58 (m, 1H, H3), 3.39 (m, 2H, H2, H5), 2.13–
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4.17. (1R,2S,3R,5R)-8-Azabicyclo[3.2.1]octane-1,2,3-triol (1)
To a stirred solution of liquid NH3 at ꢀ78 °C was consecutively
added a solution of 30 (0.22 g, 0.61 mmol) in THF (5 mL) and so-
dium (111 mg, 4.83 mmol, 8 equiv) in small portions which pro-
duced a blue solution. The reaction mixture was stirred at ꢀ78 °C
for overall 1 h, and then NH4Cl (solid) was added until the blue col-
our disappeared. The solution was allowed to warm to rt, filtered
and concentrated. The crude product was partly purified by flash
column chromatography (water/isopropanol/EtOAc 1:2:3) to yield
the desired product 1 along with NH4Cl. The resulting residue was
purified by ion exchange chromatography (Amberlite IR 120, H+)
and released with 2.5% ammonium hydroxide to give 1 (46 mg,
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47%) as a clear oil. ½a D20
ꢀ13 (c 1.0, H2O). Rf (H2O/isopropanol/EtOAc
ꢃ
1:1:1) 0.21. 1H NMR (400 MHz, D2O): dH (ppm) 3.71 (ddd, 1H, J
6.4 Hz, J 8.4 Hz, J 15.2 Hz, H3), 3.50 (m, 1H, H5), 3.42 (d, 1H, J
8.8 Hz, H2), 2.02 (m, 3H, H4, H6, H7), 1.53 (m, 3H, H40, H60, H70).
13C NMR (100 MHz, D2O): dC (ppm) 90.8 (C1), 79.4 (C2/C3), 69.8
(C3/C2), 51.4 (C5), 39.5, 28.8, 26.4 (C4,C6,C7). HRMS(ES+): calcd
for C7H13NO3: 160,0974, found 160.0974. The optical rotation
and spectroscopic data were in agreement with literature
data.2,15,16
Acknowledgements
We are grateful for support from The Faculty of Science and
OChem Graduate School, Aarhus University and the Carlsberg
Foundation.
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Supplementary data
Supplementary data (1H and 13C NMR spectra for compounds
14, 20–31 and for Calystegine A3 (1)) associated with this article