General access to polyhydroxylated nortropane derivatives through hetero Diels-Alder cycloadditions. Part 3: Synthesis of natural (+)-calystegine B2

Article abstract of DOI:10.1016/S0957-4166(99)00204-9

Cycloaddition of chiral nitroso derivatives with cyclohepta-1,3-diene gave one single stereoisomer with an excellent selectivity. The structures including absolute configurations have been assigned by spectroscopy and X-ray crystallography. These studies have been applied to the total synthesis of the naturally occurring calystegine B₂.

Full text of DOI:10.1016/S0957-4166(99)00204-9

Pergamon
Tetrahedron: Asymmetry 10 (1999) 2165–2174
General access to polyhydroxylated nortropane derivatives
through hetero Diels–Alder cycloadditions. Part 3: Synthesis of
natural (+)-calystegine B2
Thomas Faitg,a Josette Soulié,a,∗ Jean-Yves Lallemand a and Louis Ricard b
aD.C.S.O., U.M.R. 7652 C.N.R.S. Ecole Polytechnique 91128 Palaiseau Cedex, France
bD.C.P.H., U.M.R. 7653 C.N.R.S. Ecole Polytechnique 91128 Palaiseau Cedex, France
Received 6 May 1999; accepted 19 May 1999
Abstract
Cycloaddition of chiral nitroso derivatives with cyclohepta-1,3-diene gave one single stereoisomer with an
excellent selectivity. The structures including absolute configurations have been assigned by spectroscopy and
X-ray crystallography. These studies have been applied to the total synthesis of the naturally occurring calystegine
B2. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
Nitroso compounds are known to behave as good dienophiles in hetero Diels–Alder cycloadditions
to furnish bicyclo-dihydroxazines.1 We have shown in a previous communication that the resulting
adducts are effective precursors of calystegines in their racemic form (Scheme 1).2 Calystegines are
chiral polyhydroxylated nortropanic compounds, and the absolute configuration of natural calystegine
B2 has been established as (1R,2S,3R,4S,5R).3 Following our preliminary approach the chirality could
be introduced in several ways; one possibility is to introduce it during the Diels–Alder cycloaddition
involving a chiral nitroso compound. Among the numerous chiral precursors of nitroso compounds that
are most often used, we chose to test compounds 1, 2 and 3.
∗
Corresponding author. Fax: (33) 01-69-33-30-10; e-mail: soulie@poly.polytechnique.fr
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00204-9

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Scheme 1. Key step of calystegines synthesis
2. Results and discussion
Amino acid-derived hydroxamic acids 1 were easily obtained through the transformation of the
corresponding commercially available N-protected amino acid methyl esters. We studied the cyclo-
addition of a nitroso compound derived from L-alanine4 on cyclohepta-1,3-diene chosen as the model
(Scheme 2). NMR studies (COSY and HETCOR) showed that the products obtained are a mixture of
two diastereoisomers 5 (2:5) which could not be separated by chromatography. These results led us to
examine other nitroso compounds such as mandelic derivatives 2. The two enantiomeric methyl esters
are cheap and commercially available. The corresponding hydroxamic acids are easy to prepare. Several
authors5 have studied this cycloaddition on cyclopentadiene and (or) cyclohexa-1,3-diene, and have
obtained interesting selectivity at low temperature with cyclohexadiene. These results have prompted
us to attempt the cycloaddition on our cyclohepta-1,3-diene model, under similar temperature conditions
(Scheme 3).
Scheme 2. a: (n-C4H9)4NIO4, CH3OH, 0°C
Scheme 3. a: (n-C4H9)4NIO4, CH2Cl2:CH3OH (3:1)
As exemplified in Table 1, the results obtained with cyclohepta-1,3-diene at −90°C, are very good
(entry 3, Table 1): the structure of compounds 6a and 6b was determined by infra-red spectroscopy and
extensive NMR studies including COSY and HETCOR experiments. The infra-red spectra of compounds
6a and 6b indicate the presence of a hydrogen bond between the hydroxyl and carbonyl functions of the
mandelic moiety. Concerning the minor isomer, the 1H NMR spectrum shows that the axial H-2 hydrogen
(H-2a) is strongly shielded (δ=0.5 ppm) by the phenyl ring. These infra-red and NMR results allow us to
assign an unambiguous structure 6b for the minor isomer and accordingly 6a for the main product.
The cycloadducts 6a and 6b can be synthesised individually by an alternative route. A few years ago
Kresze6 described chiral nitroso Diels–Alder cycloadditions with chiral 1-chloro-1-nitroso substrates.

T. Faitg et al. / Tetrahedron: Asymmetry 10 (1999) 2165–2174
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Table 1
Variation of diastereoisomeric excess versus temperature
The mannose derivative 7 proved to be one of the most effective auxiliaries. This dienophile is equally
reactive with cyclic and acyclic dienes, affording adducts with very high enantiomeric excesses. Interest-
ingly, the ribose derivative 9 permits the other enantiomer to be obtained under the same conditions
with the same enantiomeric excess. These chloronitroso compounds react smoothly with the cyclohepta-
1,3-diene (Scheme 4). The enantiomeric oxazines (−)-10 and (+)-10 have been coupled with (R)-
mandelic acid, in the presence of N,N0-dicyclohexylcarbodiimide (DCC), according to the method used
by Defoin et al.5a in the case of cyclohexadiene. The yields are good and the compounds are identical to
those obtained by cycloaddition with nitrosomandelic derivatives. X-Ray diffraction analysis of the two
compounds 6a and 6b is in good agreement with the above described results (Fig. 1).
Scheme 4. a: t-C4H9OCl; b: cyclohepta-1,3-diene, ethanol; c: (R)-mandelic acid, DCC
These good selectivities observed with cyclohepta-1,3-diene have encouraged us to carry out the same
reactions on the trisubstituted cycloheptadiene 11, precursor of calystegine B2.2b With the mandelic
derivative we obtained a single cycloadduct, but the yield, as yet unoptimised, remains very poor (15%).
On the other hand, with sugar derivative 3 the reaction works better and the dihydrooxazine 12 is obtained
readily (67%). To confirm the enantioselectivity of the reaction, the compound 12 was derivatised with
(S)-mandelic acid, to give only one diastereoisomer 13 in good yield. This compound has the opposite
specific rotation to the compound (−)-13 (Scheme 5). The crystal structure of (+)-12 has allowed us to
attribute the absolute configuration given in Fig. 2. To complete the synthesis of natural calystegine B2
the free dihydroxazine 12 was protected as its benzylcarbamate derivative and the subsequent steps are
identical to those previously described for the racemic compound (Scheme 6).2b,3

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T. Faitg et al. / Tetrahedron: Asymmetry 10 (1999) 2165–2174
Figure 1. Crystal structure analyses of 6a and 6b
Scheme 5. a: 3, t-C4H9OCl; b: 2, (n-C4H9)4NIO4, CH2Cl2:CH3OH (3:1); c: (S)-mandelic acid, DCC
This synthesis of natural calystegine B2 shows a significant improvement: 12 steps (instead of 173b
and 213a) and a satisfactory 13% overall yield. Furthermore, this scheme has the potential to be easily
generalised to several other calystegines such as C1.
3. Experimental
NMR spectra were recorded in CDCl3 on Bruker WP 200 and AM 400 spectrometers. The chemical
shifts of 1H NMR signals δ are reported in ppm (TMS as internal standard, δ=0). Coupling constants J
are reported in hertz. The abbreviations s, d, t, m and br signify: singlet, doublet, triplet, multiplet and
broad, respectively. 13C NMR spectra were recorded on the same instruments. 13C NMR chemical shifts
are expressed in ppm, reported from the central peak of deuterochloroform (77.1 ppm). The numbering
sequence used for reporting NMR parameters is the same as that used for calystegines as indicated in

T. Faitg et al. / Tetrahedron: Asymmetry 10 (1999) 2165–2174
2169
Figure 2. Crystal structure analysis of (+)-12
Scheme 6. a: C6H5CH2OCOCl, CH2Cl2, aq. Na2CO3; b: Mo(CO)6, CH3CN:H2O (9:1); c: PCC, CH2Cl2; d: HF, H2O:CH3CN
(9:1); e: H2, Pd/C 10%, CH3OH, 4 days
Scheme 3 for the compound 6b. IR spectra were recorded on a Perkin–Elmer FT 1600 instrument and
are reported in terms of frequency of absorption (ν, cm−1). Low resolution mass spectra (MS) were
recorded on a Hewlett–Packard HP 5989B spectrometer under chemical ionisation (NH3) conditions.
High resolution mass spectra (HRMS) were recorded on a ZAB HFQ VG apparatus. Optical rotations
were measured on a Perkin–Elmer 241 polarimeter in a 1 dm cell. Melting points were determined on a
Büchi 510 apparatus and are uncorrected.
All reactions were carried out under an inert atmosphere. Dry solvents were freshly distilled before
use. Methanol was distilled from magnesium methoxide. Dichloromethane was distilled from P2O5.
All reactions were monitored by thin layer chromatrography carried out on Merck silica gel plates
(Ref. 5549) using 5% ethanolic phosphomolybdic acid/heat as developing agent. Merck silica gel (Ref.
9385) was used for flash chromatography.
D-(+)-Mannose and D-(−)-ribose were purchased from Lancaster, (R)- and (S)-mandelic acid from
Acros, cyclohepta-1,3-diene from Fluka and N-(t-butoxycarbonyl)-L-alanine methyl ester from Al-

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T. Faitg et al. / Tetrahedron: Asymmetry 10 (1999) 2165–2174
drich. N-(t-Butoxycarbonyl)-L-alanine-N-hydroxyamide 4 was prepared according to the literature.4
Colourless crystals. Mp 97°C; [α]D=+23 (c=1.0, methanol). (2R)-2-Hydroxy-2-phenylacetohydroxamic
acid 2 was prepared according to the literature.5a Mp 136°C (mp 155°C,5a 137–139°C5c); [α]D=−44
(c=0.5, methanol) ([α]D=−48 (c=0.6, methanol),5a [α]D=−63 (c=1.6, water)5c). N-Hydroxy-2,3:5,6-
di-O-isopropylidene-D-mannonimido-1,4-lactone 3 was prepared according to the literature.8–10 N-
Hydroxy-2,3-O-isopropylidene-5-O-trityl-D-ribonimido-1,4-lactone 8 was prepared according to the
literature.7–9 (5R,6S,7S)-5,7-Dibenzyloxy-6-[(t-butyldimethylsilyl)oxy]cyclohepta-1,3-diene 12 was pre-
pared according to the literature.2b
3.1. Mixture of (1R,5S)- and (1S,5R)-3-[N-(t-butoxycarbonyl)-L-alanyl]-9-oxa-8-azabicyclo[3.2.2]-
non-6-ene 5
A solution of 4 (2.5 mmol, 0.5 g) in methanol (25 mL) was added to a mixture of tetrabutylammonium
periodate (2.5 mmol, 1.1 g), cyclohepta-1,3-diene (12.4 mmol, 1.33 mL) and methanol (25 mL), cooled
to 0°C in an ice-water bath. A yellow colour began to appear quickly. Then sodium metabisulfite (0.5
M, 15 mL) was added. After the colour had disappeared, sodium carbonate (0.5 M, 50 mL) was added.
The mixture was extracted with dichloromethane, dried (MgSO4) and concentrated to give a brown solid.
This was then purified by flash chromatography (ethyl acetate:cyclohexane, 30:70) to give 5. Yield: 0.62
g (85%). 1H NMR (400 MHz): major isomer: 6.35 (dd, 3J(H-7, H-6)=6.1 Hz, 3J(H-7, H-1)=8.9 Hz, 1H:
3
H-7), 6.20 (dd, J(H-6, H-7)=6.2 Hz, 3J(H-6, H-5)=9.25 Hz, 1H: H-6), 5.43 (s, 1H: NH), 5.16 (m, 1H:
H-5), 4.74 (m, 1H: H-1), 4.68 (m, 1H: H-20), 1.9–1.4 (m, 6H: H-2, H-3, H-4), 1.24 (d, 3J=6.8 Hz, 3H: H-
30), 1.43 (s, 9H: C(CH3)3); minor isomer: 6.28 (m, 1H: H-7), 6.25 (m, 1H: H-6), 5.43 (s, 1H: NH), 5.24
3
(m, 1H: H-5), 4.74 (m, 1H: H-1), 4.68 (m, 1H: H-20), 1.9–1.4 (m, 6H: H-2, H-3, H-4), 1.33 (d, J=6.8
Hz, 3H: H-30), 1.43 (s, 9H: C(CH3)3); 13C NMR (100 MHz): major isomer: 168.6 (C-10), 156.0 (C_O
carbamate), 130.2, 126.7 (C-6, C-7), 79.3 (C(CH3)3), 77.0 (C-1), 51.1 (C-5), 47.3 (C-20), 30.0–28.5 (C-
2, C-3, C-4), 29.1 (C(CH3)3), 18.6 (C-30); minor isomer: 168.6 (C-10), 156.0 (C_O carbamate), 129.3,
127.5 (C-6, C-7), 79.3 (C(CH3)3), 77.0 (C-1), 50.4 (C-5), 47.2 (C-20), 30.0–28.5 (C-2, C-3, C-4), 29.1
(C(CH3)3), 18.6 (C-30).
3.2. General procedure for the Diels–Alder cycloaddition with cyclohepta-1,3-dienes
To a stirred solution of tetrabutylammonium periodate (1 mmol) and cyclohepta-1,3-diene (1.5 mmol)
in dichloromethane (25 mL), hydroxamic acid (1 mmol) in a mixture of methanol (12.5 mL) and
dichloromethane (12.5 mL) was added dropwise. After several hours, sodium sulfite (0.5 M, 10 mL)
was added, until the solution turned colourless. Finally, the mixture was treated with sodium carbonate
(1 M, 25 mL). The aqueous phase was extracted several times with dichloromethane, and the combined
organic layers were dried (MgSO4) and evaporated.
3.3. (1S,5R)-8-[(2R)-2-Hydroxy-2-phenylacetyl]-9-oxa-8-azabicyclo[3.2.2]non-6-ene 6a
The title compound was prepared at −90°C from cyclohepta-1,3-diene (1.5 mmol, 0.163 mL), tetra-
butylammonium periodate (1 mmol, 0.43 g) in dichloromethane (25 mL), and a solution of hydroxamic
acid 2 (1 mmol, 0.17 g) in a mixture of methanol (12.5 mL) and dichloromethane (12.5 mL). The crude
product was purified by flash chromatography (ethyl acetate:cyclohexane, 40:60) to give 6a as colourless
1
crystals. Yield: 0.21 g (64%). Mp 151°C (sublimation); [α]D=−43 (c=0.65, methanol); H NMR (400
MHz): 7.32–7.24 (m, 5H: Ph), 6.14 (ddd, 3J(H-6, H-5)=8.0 Hz, 3J(H-6, H-7)=7.1 Hz, 4J(H-6, H-1)=1.0

T. Faitg et al. / Tetrahedron: Asymmetry 10 (1999) 2165–2174
2171
3
3
4
Hz, 1H: H-6), 5.94 (ddd, J(H-7, H-6)=7.1 Hz, J(H-7, H-1)=6.1 Hz, J(H-7, H-5)=1.1 Hz, 1H: H-7),
5.37 (d, J=6.9 Hz, 1H: H-20), 5.17 (m, 1H: H-4), 4.47 (m, 1H: H-1), 4.35 (d, J=6.9 Hz, 1H: OH),
1.85–1.72 (m, 4H: H-2, H-4), 1.56, 1.38 (m, 2H: H-3a, H-3e); 13C NMR (100 MHz): 169.0 (C_O),
139.2, 128.2, 127.8, 127.5 (Ph), 128.9 (C-7), 127.2 (C-6), 76.6 (C-1), 71.3 (C-20), 52.0 (C-5), 29.9, 27.9
(C-2, C-4), 18.4 (C-3); IR ν-max: 3425 (OH), 3058 (HC_), 1641 (C_O), 1621 (C_C), 736 (HC_), 710
(C6H5); HRMS: calcd for C15H17NO3: 259.1208; found: 259.1207.
3
3
3.4. (1S,5R)-9-Oxa-8-azabicyclo[3.2.2]non-6-ene, hydrochloride (−)-10
A solution of t-C4H9OCl (1 mmol, 0.108 g) in dichloromethane (2.5 mL) was added dropwise at
−10°C in the dark to a stirred solution of N-hydroxy-2,3-O-isopropylidene-5-O-trityl-D-ribonimido-1,4-
lactone 8 (1 mmol) in dichloromethane (5 mL). The mixture was stirred for an additional hour at −10°C to
obtain crude 7 in solution. Then cyclohepta-1,3-diene (4 mmol, 0.43 mL) in ethanol (4 mL) was directly
added. When the blue colour had disappeared, extraction with water (3 mL), then with hydrochloric
acid (0.05 M, 1 mL), gave crude (−)-9 after evaporation of the combined aqueous layers. A sample was
1
purified according to the literature.10 Mp 149°C; [α]D=−24 (c=1.1, water); H NMR (400 MHz): 6.42
3
3
4
3
(ddd, J(H-7, H-6)=7.7 Hz, J(H-7, H-1)=6.4 Hz, J(H-7, H-5)=1.1 Hz, 1H: H-7), 6.29 (ddd, J(H-6,
3
4
H-7)=7.7 Hz, J(H-6, H-5)=6.9 Hz, J(H-6, H-1)=0.7 Hz, 1H: H-6), 4.81 (m, 1H: H-1), 4.44 (m, 1H:
H-5), 2.09, 2.00 (m, 2H: H-4a, H-4e), 1.88 (m, 2H: H-2), 1.54 (m, 1H: H-3e), 1.30 (m, 1H: H-3a); 13
C
NMR (100 MHz): 130.8 (C-7), 125.1 (C-6), 77.5 (C-1), 54.0 (C-5), 30.6 (C-2), 26.1 (C-4), 17.8 (C-
3); IR ν-max: 3010–2400 (NH2 ), 1050 (C–O), 714 (HC_); MS: m/z (%): 126 (100) [MH+], 143 (90)
+
+
[M+NH4 ]. Anal. calcd for C7H12NOCl: C, 52.02; H, 7.48; N, 8.67; found: C, 52.14; H, 7.27; N, 8.4
3.5. (1R,5S)-9-Oxa-3-azabicyclo[3.2.2]non-6-ene, hydrochloride (+)-10
This compound was synthesised according to the procedure, and on the same scale used for the
compound (−)-10, with N-hydroxy-2,3:5,6-di-O-isopropylidene-D-mannonimido-1,4-lactone 3 and was
purified as above. Yield: 81%. Mp 149°C; [α]D=+24 (c=1.0, water).
3.6. (1R,5S)-8-[(2R)-2-Hydroxy-2-phenylacetyl]-9-oxa-8-azabicyclo[3.2.2]non-6-ene 6b
To a stirred solution of (+)-10 (1 mmol, 0.16 g) in dry ethanol (3.5 mL) were added sequentially (R)-
mandelic acid (1 mmol, 0.15 g), triethylamine (1 mmol, 0.14 mL) and a solution of DCC (1 mmol, 0.21
g) in anhydrous chloroform (3.5 mL). After 24 h, at room temperature, the solid was filtered and washed
with chloroform. The filtrate was diluted with tetrahydrofuran, DCU was filtered again, the residue was
evaporated and the crude compound 6b purified by recrystallisation (ether:dichloromethane, 1:4) to give
1
6b as colourless crystals. Yield: 0.21 g (81%). Mp 71–72°C; [α]D=−114 (c=0.5, methanol); H NMR
3
3
(400 MHz): 7.40–7.27 (m, 5H: Ph), 6.34 (ddd, J(H-7, H-1)=9.1 Hz, J(H-7, H-6)=6.1 Hz, 4J(H-7, H-
5)=1.1 Hz, 1H: H-7), 6.16 (ddd, 3J(H-6, H-5)=7.1 Hz, 3J(H-6, H-7)=6.1 Hz, 4J(H-6, H-1)=1.2 Hz, 1H:
H-5), 5.29 (d, J=6.5 Hz, 1H: H-20), 5.20 (m, 1H: H-5), 4.50 (m, 1H: H-1), 4.46 (d, J=6.5 Hz, 1H:
3
3
OH), 1.68, 1.59 (m, 2×1H: H-4a, H-4e), 1.48 (m, 1H: H-2e), 1.24 (m, 2H: H-3), 0.56 (m, 1H: H-2a); 13
C
NMR (100 MHz): 167.3 (C_O), 129.8, 128.3, 128.0, 127.7 (Ph), 130.4 (C-7), 125.5 (C-6), 76.7 (C-1),
71.3 (C-10), 51.2 (C-5), 28.6 (C-4), 27.4 (C-2), 18.0 (C-3); IR ν-max: 3351 (OH), 3065 (HC_), 1643
(C_O), 1626 (C_C), 704 (C6H5); MS: m/z (%): 260 (100) [MH+], 277 (50) [M+NH4 ]. Anal. calcd for
+
C15H17NO3: C, 69.47; H, 6.61; N, 5.40; found: C, 69.26; H, 7.03; N, 5.67.

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T. Faitg et al. / Tetrahedron: Asymmetry 10 (1999) 2165–2174
3.7. (1S,2R,3R,4S,5R)-2,4-Dibenzyloxy-3-[(t-butyldimethylsilyl)oxy]-9-oxa-8-azabicyclo-[3.2.2]-non-
6-ene 12
This compound was synthesised according to the same procedure and on the same scale used for the
1
compound (+)-10. Yield: 67%; mp 96°C; [α]D=+9.6 (c=1, CHCl3); H NMR (400 MHz): 7.40–7.28
(10H: Ph), 6.58 (dd, 3J(H-7, H-6)=8.7 Hz, 3J(H-7, H-1)=7.2 Hz, 1H: H-7), 6.24 (ddd, 3J(H-6, H-7)=8.7
3
4
Hz, J(H-6, H-5)=6.6 Hz, J(H-6, H-1)=1.4 Hz, 1H: H-6), 4.74–4.61 (m, 4H: H-10, H-100), 4.46 (dd,
3J(H-1, H-7)=7.2 Hz, 3J(H-1, H-6)=1.4 Hz, 1H: H-1), 3.67 (m, 2H: H-5, H-3), 3.44 (m, 2H: H-2, H-3),
0.89 (s, 9H: (CH3)3CSi), 0.02, 0.01 (s, 2×3H: (CH3)2Si); 13C NMR (100 MHz):135.5 (C quat. Ph),
132.0 (C-7), 128.3, 127.5, 126.9 (Ph), 126.4 (C-6), 84.7 (C-2), 82.8 (C-4), 75.9 (C-3), 72.9, 70.3 (C-10,
C-100), 72.3 (C-1), 55.6 (C-5), 26.0 ((CH3)3CSi), 18.1 ((CH3)3CSi), −4.1, −4.2 ((CH3)2Si); IR ν-max:
3211 (NH), 1244 (C–Si), 1105, 1071 (C–O), 870 (C–Si); MS: m/z (%): 468 [MH+], 454.
3.8. (1S,2R,3R,4S,5R)-2,4-Dibenzyloxy-8-benzyloxycarbonyl-3-[(t-butyldimethylsilyl)oxy]-9-oxa-
8-azabicyclo[3.2.2]non-6-ene (+)-13
This compound was synthesised according to the same procedure and on the same scale used for the
compound (+)-10. Yield: 85%; [α]D=+62.3 (c=0.22, CHCl3).
3.9. (1R,2S,3S,4R,5S)-2,4-Dibenzyloxy-8-benzyloxycarbonyl-3-[(t-butyldimethylsilyl)oxy]-9-oxa-
8-azabicyclo[3.2.2]non-6-ene (−)-14
This compound was synthesised according to the same procedure and on the same scale used for the
compound 6a. Yield: 15%; [α]D=−62 (c=0.65, CHCl3); 1H NMR (400 MHz): 7.35–7.27 (m, 15H: Ph),
6.23 (t, 3J(H-6, H-7)=3J(H-6, H-5)=7.8 Hz, 1H: H-6), 6.36 (dd, 3J(H-7, H-6)=7.8 Hz, 3J(H-7, H-1)=6.0
Hz, 1H: H-7), 5.31 (d, 3J(H-2000, OH)=7.4 Hz, 1H: H-2000), 5.24 (d, 3J(H-5, H-6)=7.8 Hz, 1H: H-5), 4.79,
2
2
4.72 (d, J=11.9 Hz, 2×1H: H10 or H-100), 4.76, 4.57 (d, J=11.7 Hz, 2×1H: H10 or H-100), 4.34–4.30
(m, 2H: H-2, H-4), 4.20 (d, 3J(H-1, H-7)=6.0 Hz, 1H: H-1), 4.18 (d, J(OH, H-2000)=7.4 Hz, 1H: OH),
3
3.50 (m, 1H: H-3), 0.88 (s, 9H: (CH3)3CSi), 0.08, 0.00 (s, 2×1H: (CH3)2Si); 13C NMR (100 MHz):
165.9 (C_O), 138, 136 (C quat. Ph), 130.9 (C-6), 128.8–127.5 (Ph), 127.3 (C-7), 82.4 (C-2), 81.4 (C-
4), 75.8 (C-3), 75.4 (C-1), 73.3, 71.3 (C-10, C-100), 72.3 (C-2000), 52.4 (C-5), 25.3 ((CH3)3CSi), 16.7
((CH3)3CSi), −5.8 ((CH3)2Si); MS: m/z (%): 603 (M+·), 585, 494, 403.
3.10. (1S,2R,3R,4S,5R)-2,4-Dibenzyloxy-5-benzyloxycarbonylamino-3[(t-butyldimethylsilyl)oxy]-
cyclohept-6-en-1-ol 15
This compound was synthesised according to the same procedure and on the same scale used for the
racemic compound.1b Yield: 91%; [α]D=−23.7 (c=0.53, CHCl3).
3.11. (2S,3R,4S,5R)-2,4-Dibenzyloxy-5-benzyloxycarbonylamino-3-[(t-butyldimethylsilyl)oxy]-
cyclohept-6-en-1-one 16
This compound was synthesised according to the same procedure and on the same scale used for the
racemic compound.2b Yield: 76%; [α]D=−98.5 (c=0.25, CHCl3).

T. Faitg et al. / Tetrahedron: Asymmetry 10 (1999) 2165–2174
2173
Table 2
Crystallographic data for 6a, 6b and (+)-12
3.12. (2S,3R,4S,5R)-2,4-Dibenzyloxy-5-benzyloxycarbonylamino-3-hydroxycyclohept-6-en-1-one 17
This compound was synthesised according to the same procedure and on the same scale used for the
racemic compound.2b Yield: 85%; [α]D=−104.4 (c=0.51, CHCl3).
3.13. (+)-Calystegine B2
This compound was synthesised according to the same procedure as in the literature.3b
3.14. X-Ray structure determination for 6a, 6b and (+)-12
Crystals suitable for X-ray diffraction were obtained from methanolic solutions of the compounds.
Data were collected at 123ꢀ0.5 K on an Enraf Nonius CAD4 diffractometer. The crystal structures
were solved and refined using the Enraf Nonius MOLEN package. Positional and isotropic temperature
factors were refined for all hydrogen atoms in the final stages of least-squares analysis. Crystal data are
assembled in Table 2.

2174
T. Faitg et al. / Tetrahedron: Asymmetry 10 (1999) 2165–2174
Acknowledgements
One of us (T.F.) thanks the Ministère de l’Education Nationale et de la Technologie for a doctoral
fellowship.
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