Carbasaccharides via ring-closing alkene metathesis. A synthesis of (+)- valienamine from D-glucose

Article abstract of DOI:10.1002/(SICI)1522-2675(19990505)82:5<645::AID-HLCA645>3.0.CO;2-K

(+)-Valienamine (16) was prepared in seven steps and in an overall yield of 17% from commercially available 2,3,4,6-tetra-O-benzyl-D-glucopyranose. Stereoselective addition of vinylmagnesium bromide to the 1,3,4,5-tetra-O- benzyl-6,7-dideoxy-L-xylo-hept-6-en-2-ulose (2) gave diene 3 (86%). Ring- closing alkene metathesis of 3 in the presence of 0.15 equiv, of Grubb's catalyst 1 gave the cyclohexene 4 (58%), that was converted into (+)- valienamine (16) in three steps and in 47% yield. Similarly, ring-closing alkene metathesis of the D-mannose-derived diene 20 gave the cyclohexene 21 (89%).

Full text of DOI:10.1002/(SICI)1522-2675(19990505)82:5<645::AID-HLCA645>3.0.CO;2-K

Helvetica Chimica Acta ± Vol. 82 (1999)
645
Carbasaccharides via Ring-Closing Alkene Metathesis.
A Synthesis of (‡)-Valienamine from d-Glucose
1
by Peter Kapferer, Francisco Sarabia ), and Andrea Vasella*
Laboratorium für Organische Chemie, ETH-Zentrum, Universitätstrasse 16, CH-8092 Zürich
(‡)-Valienamine (16) was prepared in seven steps and in an overall yield of 17% from commercially
available 2,3,4,6-tetra-O-benzyl-d-glucopyranose. Stereoselective addition of vinylmagnesium bromide to the
1,3,4,5-tetra-O-benzyl-6,7-dideoxy-l-xylo-hept-6-en-2-ulose (2) gave diene 3 (86%). Ring-closing alkene
metathesis of 3 in the presence of 0.15 equiv. of Grubbꢀs catalyst 1 gave the cyclohexene 4 (58%), that was
converted into (‡)-valienamine (16) in three steps and in 47% yield. Similarly, ring-closing alkene metathesis of
the d-mannose-derived diene 20 gave the cyclohexene 21 (89%).
Introduction. ± Glycosylamines and related N-glycosyl derivatives are of limited use
as glycosidase inhibitors, due to their tendency to anomerise and to undergo hydrolysis.
Carbocyclic analogues, such as (‡)-valienamine (16), are exempt from this disadvant-
age. Thus, in our search for glycosidase inhibitors with improved characteristics as
transition-state analogues [1 ± 7], we became interested in the synthesis of six-
membered carbasaccharides. A range of methods lead to monocyclic carbapyranoses
[8a ± q] (for older reviews on carbasugar synthesis, see [8r± u]). Among the newer
methods, ring-closing alkene metathesis (RCM) [9 ± 16] seems to be particularly
promising. It has led to pyranoses [17], carbohydrate-derived oxepines [18] and
indolizidines [19][20], pyranopyranoses [21], bridged [22][23] and chain-elongated
[24][25] carbohydrates, a cyclohexene annulated to a pyranoside [26], a carbafuranose
[27], and a couple of carbapyranoses [28][29]. We intended to synthesize carbocyclic
glucose and mannose analogues by RCM, to prepare the required diene precursors
diastereoselectively, to explore the influence of the configuration and steric hindrance
on the RCM, and to apply the method to a synthesis of (‡)-valienamine (16). (‡)-
Valienamine is accessible by microbial degradation [30] or NBS-cleavage [31][32] of
validoxylamine A. It has been synthesized several times de novo [33 ± 37] and from
enantiomerically pure precursors [38 ± 46]. The two most efficient routes appear to
be the one by Fukase and Horii [45], who obtained 16 in eight steps and in 12% yield
from 2,3,4,6-tetra-O-benzyl-d-glucopyranose via intramolecular Horner-Emmons
alkenylation and the one by Nicotra et al. [44], who obtained 16 in five steps and in
22% yield from a cyclohexenone, that was prepared by a Ferrier cyclization from
methyl 4,6-O-benzylidene-2,3-di-O-benzyl-a-d-glucopyranoside in six steps and in
57% yield [40][47].
1
 Â
Current address: Departamento de Química Organica, Facultad de Ciencias, Universidad de Malaga,
)
Â
Campus de Teatinos, E-29071 Malaga.

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Helvetica Chimica Acta ± Vol. 82 (1999)
Retrosynthetic analysis revealed the cyclohexene 4 as a key intermediate and the
diene 3 as an appropriate starting material. This diene should be readily accessible
from the known ketone 2 [48]. The reduction of a similar ketone possessing a nitrile
function instead of the ethenyl moiety (NaBH4/CeCl3) proceeded with a diastereose-
lectivity of 86% [49][50], auguring well for a diastereoselective addition of vinyl-
magnesium bromide to 2. The epimer 8 of 4 has been transformed by Nicotra et al. into
(‡)-valienamine [44] and by McAuliffe and Stick into a 4-epivalienamine derivative
[51]. Several protected derivatives of 4 have been transformed into valiolamine
derivatives [52].
Results and Discussion. ± The ketone 2 is readily obtained from 2,3,4,6-tetra-O-
benzyl-d-glucopyranose [48]. Addition of vinylmagnesium bromide to 2 in THF
at 788 gave the epimeric dienes 3 and 7 in 86 and 1% yield, respectively (Scheme 1).
1
The constitution of the products is evidenced by their H- and 13C-NMR spectra.
The configuration of 3 and 7 was tentatively assigned by analogy to the above
mentioned reduction [49][50], where the nucleophile attacked preferentially from the
re face.
Ring-closing alkene metathesis of the homogeneous dienes 3 and 7 in the presence
of Grubbꢀs catalyst 1 [53] (0.15 equiv. for 3, 0.3 equiv. for 7) gave the cyclohexenes 4 and
8 [44] in 58 and 66% yield, respectively. While the d-gluco-isomer 8 was colourless, the
l-ido-isomer 4 was isolated as a green oil, contaminated with traces of ruthenium
oxides. Benzylation of 4 and 8 gave the fully protected 5 and 9 in 88 and 49% yield,
1
respectively. The optical rotation and H-NMR spectrum of 8 matched the data
reported by Nicotra et al. [44], thus establishing the (6R)-configuration of 7, the (4R)-
configuration of 8, and, indirectly, the (6S)-configuration of 3 and the (4S)-
configuration of 4.
3
The vicinal coupling constants for the ring H of 4, 5, 8, and 9 indicate a H2
conformation2) (Table 1). The alkenyl H-atoms of 8 appear as a s at 5.74 ppm, while
those of 4 appear as two ddꢀs at 5.92 (H C(6)) and 5.69 ppm (H C(5), J(5,6) ˆ
10.3 Hz). The geminal coupling constants for H C(7) of 4 and 5, where the
benzyloxymethyl (BnOCH2) groups are pseudoequatorial, are smaller than those of
the epimers 8 and 9 (DJ ˆ 0.6 to 1.0 Hz), possessing pseudoaxial BnOCH2 groups. This
is rationalised by different rotameric equilibria (Fig.). Conformations I and II should
be about equally populated in both epimeric series, while III is destabilized for 8 and 9,
but not for 4 and 5. In conformation III, the tertiary OR group is gauche to both
methylene H-atoms. It is known [54][55] that such an orientation of an electron-
withdrawing substituent leads to a decreased (absolute) geminal coupling constant.
Such a dependence of the geminal coupling constant on the configuration of the
quarternary center of 1-(hydroxymethyl)cyclohex-2-en-1-ol derivatives has been
reported by Ogawa et al. for 6 (J (7,7') ˆ 10.8 Hz) and 10 (J (7,7') ˆ 11.8 Hz) [56],
2
)
The systematic numbering differs between 4, 6, 8, and 10 on the one hand, and 5 and 9 on the other; the
locants of the cyclohexenes in Scheme 1 used for the discussion of the conformation are those of the
unprotected cyclohexenes 6 and 10 with the exception for the locant for the HOCH2 group that is 7.
Similarly, the HOCH2 group of the dienes is designated as C(9).

Helvetica Chimica Acta ± Vol. 82 (1999)
647
Scheme 1
a) H2CˆCHMgBr, THF; 86% of 3, 1% of 7. b) 1, CH2Cl2; 58% of 4; 66% of 8. c) NaH, DMF, then BnBr; 88% of
5; 49% of 9. d) CCl3CONCO, CH2Cl2, then K2CO3, MeOH/H2O; 86%. e) Ph3P, Et3N, CBr4, CH2Cl2. f) BnOH;
70% of 14 (from 11). g) Me3Al; 77% of 15 (from 11). h) 14, Na, NH3/THF; 78%. i) Ac2O, pyridine; 86%.
and by Tagmose and Bols for the 1-deoxy analogues of 4 and 8 (J(7,7') ˆ 8.5 vs.
9.5 Hz)3), and for the corresponding acetates (J(7,7') ˆ 8.5 vs. 10 Hz) [57].4)
The data for the 1-deoxy analogue of 8 (J(2,3)ˆ 6.5 Hz) indicate that it does not adopt a 3H2 conformation.
Paulsen and co-workers [52] claimed a synthesis of 5 by benzylation of 6, which was synthesized by
stereoselective addition of a 2-lithio-1,3-dithian to (3S,4R,5S)-4,5,6-tris(benzyloxy)cyclohex-2-en-1-one.
Paulsenꢀs data for 6 are at variance with the data reported by Ogawa et al. [56] for 6 and for 10. Similarly,
Paulsenꢀs data for 5 differ from our data for 5 and for 9, the origin for the difference remaining unclear, as
the original samples and spectra are no longer available. We thank Prof. Dr. H. Paulsen for pertinent
discussions.
3
)
)
4

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Table 1. Selected NMR (CDCl3) Chemical Shifts [ppm], Coupling Constants [Hz], and Optical Rotations
(CHCl3) of 4, 5, 8, 9, and 212)
4
5a)
8
9a)
21
H
H
H
H
H
H
C(1)
C(2)
C(3)
C(5)
C(6)
C(7)
4.20
4.02
3.76
5.69
5.92
3.38
3.30
2.80
72.97
8.1
2.2
1.9
10.3
10.3
8.7
4.19
4.49
3.97
5.76
5.90
3.73
3.53
±
4.20
3.87
3.76
5.74
5.74
3.83
3.63
2.74
75.77
7.2
0
0
10.3
0
9.3
4.22
4.47 ± 4.38
3.97
5.67
5.84
4.14
3.76
±
4.16
3.94
4.26
5.79
5.95
3.46
3.43
3.10
73.08
3.7
0
5.0
9.7
10.0
9.3
H' C(7)
OH
C(4)
J(1,2)
J(1,5)
J(1,6)
J(2,3)
J(5,6)
J(7,7')
[a]2D5
78.13
7.5
1.9
±b)
7.8
2.2
1.9
10.3
2.5
10.6
10.3
8.7
10.6
9.7
70.8
20.1
8.7
26c)
35.2
c
a) In C6D6. b) Not determined. ) [a]2D0 Value.
Figure. Rotational equilibria for the BnOCH2 group of 4 and 5, and 8 and 9
To transform 4 into (‡)-valienamine (16), we applied Ichikawaꢀs method for the
conversion of allylic alcohols to allylic amines by a [3,3]-sigmatropic rearrangement of
allylic cyanates [58 ± 60] that has proven useful in the synthesis of 3-deoxyvalienamine
[57].5) Thus, treatment of the tertiary allylic alcohol 4 with trichloroacetyl isocyanate in
CH2Cl2 at 08, followed by hydrolysis with K2CO3 in aqueous MeOH gave 86% of the
carbamate 11. Dehydration of 11 with Ph3P, Et3N, and CBr4 in CH2Cl2 at 208 led to the
isocyanate 13 by spontaneous rearrangement of the bona fide cyanate 12. The
isocyanate 13 was treated in situ with PhCH2OH to yield 70% of the protected (‡)-
valienamine 14. Alternatively, in situ treatment of 13 with Me3Al yielded 77% of N-
acetyl-tetra-O-benzylvalienamine 15 [32]. Its 1H- and 13C-NMR spectra were identical
to those of an authentic sample6), confirming the (4S)-configuration of 4 and the (6S)-
configuration of 3. The vicinal coupling constants for the ring H-atoms of 14 (J(1,2) ˆ
4.3, J(2,3) ˆ 7.5, J(3,4) ˆ 4.7 Hz) and 15 (J(1,2) ˆ 4.1, J(2,3) ˆ 7.2, J(3,4) ˆ 4.7 Hz)
indicate an equilibrium of the 3H2 and 2H3 conformers. The vicinal coupling constants of
5
)
)
Overman rearrangement [61 ± 64] of the trichloroacetimidate derived from 4 proceeded in low yields.
The authentic sample was prepared from validoxylamine A following the protocol of Ogawa et al. [32]. We
thank Dr. A. G. OꢀSullivan, Novartis Agro, Basel, for a generous gift of validoxylamine A.
6

Helvetica Chimica Acta ± Vol. 82 (1999)
649
the individual conformers (3H2: J(1,2) ˆ 2.8, J(2,3) ˆ 4.2, J(3,4) ˆ 2.8 Hz; 2H3: J(1,2) ˆ
7.8, J(2,3) ˆ 9.8, J(3,4) ˆ 4.3 Hz) were calculated by gas-phase molecular modelling
(Macromodel version 6.0, MM3* force-field [65]).
The benzyl carbamate 14 was readily deprotected under Birch conditions [45].
Workup following the procedure of Paulsen and Heiker [39] gave (‡)-valienamine (16)
in 78% yield as a slightly yellow solid. The optical rotation, and the 1H- and 13C-NMR
spectra of 16 and of the pentaacetate 17 were in complete agreement with the published
data [30][35][44][45][66].
For the synthesis of the d-mannose-derived l-gulo-configured 21, we subjected
manno-heptenitol 18 [67] to a Moffatt oxidation [68][69], similarly as described for the
synthesis of 2 [48]. This gave the ketone 19 (87%; Scheme 2). Addition of vinyl-
magnesium bromide to 19 yielded 95% of the diene 20. The diastereoselectivity of this
addition was higher than that observed for the addition to 2. Only traces of a by-product
were detected on TLC. The configuration of 20 was assigned tentatively by analogy to
that of 3.
Scheme 2
a) DMSO, DCC, pyridine, CF3CO2H, toluene; 87%. b) H2CˆCHMgBr, THF; 95%. c) 1, CH2Cl2; 89%.
The C(6) OH signals of 20 and 3 are nearly isochronous. Their chemical shift is
larger than that of 7 (Dd ca. 0.65 ppm) (Table 2), indicating a stronger intramolecular
1
H-bond. The IR bands (3: 3468, 20: 3462 cm ) agree well with a six-membered
intramolecular H-bond to BnO C(4), and thus with the conformations depicted in
Schemes 1 and 2. The chemical shift for C(6) OH of 7 suggests a five-membered H-
bond to BnO C(9). This implies that H C(9) of 3 and 20 (but not of 7) are both
gauche to the tertiary OH group (as in conformer III (Fig.) of 4 and 5). Indeed, smaller
(absolute) J(9,9') values are observed for 3 and 20 (8.7 Hz) than for 7 (9.3 Hz). Thus, 20
should possess the same configuration at C(6) as 3. In keeping with that, the difference
between the optical rotation of 20 and 19 (D([a]2D5 ) ˆ 40.7) is very similar to that
between 3 and 2 (D([a]2D5 ) ˆ 34.5).
RCM of 20 in the presence of 0.15 equiv. of 1 gave the cyclohexene 21 in 89% yield
3
as a green oil. The vicinal coupling constants for the ring H of 21 indicate a H2
conformation as in 4 (Table 1). The chemical shifts for H C(7), H' C(7), and C(6) of
21 show a stronger similarity to the values for 4 than to those for 8 (Table 1). In
cyclohexanes, the C-atoms carrying an axial substituent absorb at higher field than
those with equatorial substituents, and this effect is larger for oxy substituents than for
alkyl substituents [70]. Thus, the upfield shift for C(6) of 4 and 21 as compared to 8
agrees with a pseudoaxial tertiary OH group. The assignment of the configuration of 21
was corroborated by a NOE experiment. Upon irradiation at 3.45 ppm (H C(7) and

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Helvetica Chimica Acta ± Vol. 82 (1999)
Table 2. Selected NMR (CDCl3) Chemical Shifts [ppm], Coupling Constants [Hz], and Optical Rotations
(CHCl3) of 3, 7, and 202)
3
7
20
H
C(1)
5.30
5.20
5.83
4.07
3.88 ± 3.84
3.88 ± 3.84
3.63
3.29
3.74
10.3
17.4
7.8
6.5
3.5
5.26
5.25
5.94
4.09
3.74 ± 3.68
3.99
3.74 ± 3.68
3.28
3.09
17.1
5.47 ± 5.42
5.47 ± 5.42
6.02 ± 5.91
4.05
3.90
4.07
H' C(1)
H
H
H
H
H
C(2)
C(3)
C(4)
C(5)
C(9)
3.73
3.28
H' C(9)
OH
3.75
a
J(1,2)
J(1',2)
J(2,3)
J(3,4)
J(4,5)
J(9,9')
[a]2D5
)
)
a
10.6
7.5
4.4
5.9
9.3
7.5
7.2
2.5
8.7
4.5
8.7
35.2
a
)
a) Not determined.
H' C(7) at 3.43 and 3.46 ppm), a NOE of 10% was observed for H C(3), whereas no
effect was observed for H C(2).
The higher yield for the RCM of 20 as compared to the one of 3 is presumably due
to the different conformational strain of the bicyclic intermediate of the cyclization.
Miller and Grubbs have shown that the relative configuration of the centers between
the reacting double bonds can have a profound effect on the RCM of a diene [71].
We thank the Swiss National Science Foundation and F. Hoffmann-La Roche AG, Basel, for generous
support and Dr. B. Bernet for checking the manuscript.
Experimental Part
General. Solvents were freshly distilled from CaH2 (CH2Cl2, MeOH, DMF) or Na/benzophenone (THF,
toluene). All reactions were carried out under Ar, unless stated otherwise. Anal. TLC: Merck precoated silica
gel 60 F-254 plates; detection by treatment with a soln. of 5% (NH4)6Mo7O26 ´ 4H2O, 0.1% Ce(SO4)2 ´ H2O, in
10% H2SO4 soln. Flash chromatography (FC): silica gel 60 (40 ± 63 mm). M.p.: uncorrected. Optical rotations:
1-dm cell, 589 nm. FT-IR Spectra: absorption in cm 1. NMR Spectra: chemical shifts in ppm relative to TMS
(1H, 13C); coupling constants in Hz. NOE Experiments allowed unambiguous assignments of all 1H-NMR
signals of 4 and 21, and HSQC.GRASP spectra unambiguous assignments of the 13C-NMR signals of 4 and 21.
The assignments of the other cyclohexenes are based on comparisons with 4 and 21. An * indicates that the
assignments may be interchanged. MS: FAB in 3-nitrobenzyl alcohol (NOBA) matrix.
3,4,5-Tri-O-benzyl-6-C-[(benzyloxy)methyl]-1,2,7,8-tetradeoxy-d-gluco-octa-1,7-dienitol (3) and 3,4,5-Tri-
O-benzyl-6-C-[(benzyloxy)methyl]-1,2,7,8-tetradeoxy-l-ido-octa-1,7-dienitol (7). A cooled ( 788) soln. of
2
(2.32 g, 4.32 mmol) in THF (43 ml) was treated dropwise with 1m vinylmagnesium bromide in THF (6.5 ml,
6.5 mmol), stirred for 45 min at this temp., warmed to 08, and treated with Et2O (80 ml) and sat. aq. NH4Cl soln.
(80 ml). The org. phase was separated, washed with brine (50 ml), dried (MgSO4), and evaporated. FC (300 g
of silica gel; hexane/AcOEt 6 : 1) of the oily residue (2.7 g) gave 7 (22 mg, 1%) and 3 (2.11 g, 86%).
Data of 3: colourless oil. Rf (hexane/AcOEt 3 :1) 0.57. [a]2D5 ˆ 35.2 (c ˆ 3.3, CHCl3). FT-IR (3%, CHCl3):
3448m, 3089w, 3066w, 3007m, 2911w, 2866m, 1951w, 1873w, 1811w, 1732w, 1639w, 1604w, 1496m, 1454m, 1422w,
1398w, 1351m, 1093s, 1028m, 996m, 934m, 822w, 606w, 515w. 1H-NMR (300 MHz, CDCl3): 7.36 ± 7.23 (m,
20 arom. H); 5.97 (dd, J ˆ 17.1, 10.6, H C(7)); 5.83 (ddd, J ˆ 17.4, 10.3, 7.8, H C(2)); 5.47 (dd, J ˆ 17.1, 1.9,

Helvetica Chimica Acta ± Vol. 82 (1999)
651
H
C(8)); 5.30 (br. dd, J ˆ 10.3, 1.9, H C(1)); 5.20 (br. dd, J ˆ 17.4, 1.9, H' C(1)); 5.19 (dd, J ˆ 10.6, 1.9,
H' C(8)); 4.84 (d, J ˆ 11.2, PhCH); 4.78 (d, J ˆ 11.5, PhCH); 4.65 ± 4.61 (m, 3 PhCH); 4.48 (d, J ˆ 12.1,
PhCH); 4.43 (d, J ˆ 11.8, PhCH); 4.35 (d, J ˆ 11.8, PhCH); 4.07 (br. dd, J ˆ 7.8, 6.5, H C(3)); 3.88 ± 3.84
(m, H C(4), H C(5)); 3.74 (s, OH); 3.63 (d, J ˆ 8.7, CH C(6)); 3.29 (d, J ˆ 8.7, CH' C(6)). 13C-NMR
(75 MHz, CDCl3): 140.32 (d, C(7)); 139.05(s); 138.56(s); 138.47(s); 138.34(s); 135.67 (d, C(2)); 128.65 ±
127.62 (several d); 119.66 (t, C(1)); 114.88 (t, C(8)); 81.83(d); 81.23(d); 78.35(d); 77.98 (s, C(6)); 74.76(t);
‡
‡
74.54(t); 74.49(t); 73.52(t); 70.70(t). FAB-MS (NOBA): 587 (9, [M ‡ Na] ), 565 (53, [M ‡ 1] ), 457
‡
(18, [M BnO] ), 267(7), 241(9), 197(10), 181(100), 173(16), 154(11), 147(15), 107(9). Anal. calc. for
C37H40O5 (564.72): C 78.70, H 7.14; found: C 78.87, H 7.35.
1
Data of 7: colourless oil. Rf (hexane/AcOEt 3 :1) 0.62. H-NMR (300 MHz, CDCl3): 7.36 ± 7.21 (m, 20 ar-
om. H); 6.07 (dd, J ˆ 17.4, 10.9, H C(7)); 5.94 (ddd, J ˆ 17.1, 10.6, 7.5, H C(2)); 5.45 (dd, J ˆ 17.4, 2.2,
H
C(8)); 5.26 (br. dd, J ˆ 17.1, 1.0, H C(1)); 5.25 (br. dd, J ˆ 10.6, 1.0, H' C(1)); 5.23 (dd, J ˆ 10.9, 2.2,
H' C(8)); 4.82 (d, J ˆ 11.5, PhCH); 4.68 (d, J ˆ 11.5, PhCH); 4.64 (d, J ˆ 11.8, PhCH); 4.62 ± 4.43 (m, 4
PhCH); 4.35 (d, J ˆ 11.8, PhCH); 4.09 (br. dd, J ˆ 7.5, 4.4, H C(3)); 3.99 (d, J ˆ 5.9, H C(5)); 3.74 ± 3.68
(m, H C(4), CH C(6)); 3.28 (d, J ˆ 9.3, CH' C(6)); 3.09 (s, OH). 13C-NMR (75 MHz, CDCl3): 139.43;
138.99; 138.52; 138.34; 138.03 (C(7)); 136.09 (C(2)); 128.62 ± 127.45; 118.96 (C(1)); 115.92 (C(8)); 81.67; 80.83;
79.32; 74.78; 74.75; 74.65; 73.52; 70.64; s of C(6) hidden by noise or other signals.
(1d)-(1,3,4/2)-1,2,3-Tri-O-benzyl-4-C-[(benzyloxy)methyl]cyclohex-5-ene-1,2,3,4-tetrol (4). A soln. of
3
(2.20 g, 3.89 mmol) in CH2Cl2 (200 ml) was degassed by puckering with N2, treated with 1 (0.48 g, 0.54 mmol),
stirred at r.t. for 7 d, and evaporated. FC (300 g of silica gel; hexane/AcOEt 3 :1) of the residual oil gave 3 (0.5 g,
23%) as a dark green oil and 4 (1.25 g) as a dark-green oil. An additional FC (150 g of silica gel, as above) of the
latter gave 4 (1.2 g, 58%). Green oil. Rf (hexane/AcOEt 3 :1) 0.33. [a]2D5 ˆ 70.8 (c ˆ 1.51, CHCl3). FT-IR (1.5%,
CHCl3): 3538m, 3089m, 3066m, 3008m, 2863m, 1951w, 1875w, 1811w, 1731w, 1604w, 1496m, 1454m, 1393w,
1361m, 1294w, 1136m, 1064s, 1028m, 929w, 912w, 857w, 628w, 609w, 548w, 537w, 525w, 518w, 511w, 503w.
1H-NMR (300 MHz, CDCl3): 7.37 ± 7.16 (m, 20 arom. H); 5.92 (dd, J ˆ 10.3, 1.9, H C(6)); 5.69 (dd, J ˆ 10.3,
2.2, H C(5)); 4.95 (d, J ˆ 10.9, PhCH); 4.93 (d, J ˆ 10.9, PhCH); 4.86 (d, J ˆ 11.2, PhCH); 4.72 (s, PhCH2);
4.48 (d, J ˆ 12.5, PhCH); 4.46 (d, J ˆ 10.9, PhCH); 4.38 (d, J ˆ 12.1, PhCH); 4.20 (dt, J ˆ 8.1, 2.1, irrad. at
5.92 ! NOE of 6%, H C(1)); 4.02 (dd, J ˆ 10.3, 8.1, H C(2)); 3.76 (d, J ˆ 10.3, H C(3)); 3.38 (d, J ˆ 8.7,
CH C(4)); 3.30 (d, J ˆ 8.7, irrad. at 5.69 ! NOE of 3%, CH' C(4)); 2.80 (s, OH). 13C-NMR (75 MHz,
CDCl3, assignment based on HSQC.GRASP): 139.09(s); 138.75(s); 138.34(s); 138.03(s); 131.24 (d, C(6));
129.86 (d, C(5)); 128.67 ± 127.79 (several d); 81.57 (d, C(2)); 80.28 (d, C(1)); 78.39 (d, C(3)); 75.85(t); 75.51(t);
‡
73.53 (t, CH2 C(4)); 73.47(t); 72.97 (s, C(4)); 72.01(t). FAB-MS (NOBA): 559 (6, [M ‡ Na] ), 535 (15, [M
‡
‡
‡
‡
‡
1] ), 519 (36, [M OH] ), 429 (5, [M BnO] ), 412 (15, [M OH BnO] ), 411 (17, [M H2O BnO] ),
321(26), 297(17), 291(11), 271(15), 213(17), 197(12), 181(100). Anal. calc. for C35H36O5 (536.67): C 78.33,
H 6.76; found: C 78.42, H 6.91.
(1l)-(1,2,4/3)-1,2,3,4-Tetra-O-benzyl-1-C-[(benzyloxy)methyl]cyclohex-5-ene-1,2,3,4-tetrol (5). A cooled
(08) suspension of oil-free NaH (washed with hexane, 25 mg, 1.04 mmol) in DMF (5 ml) was treated with a soln.
of 4 (257 mg, 0.48 mmol) in DMF (6 ml) and stirred for 30 min. After warming to r.t., the mixture was treated
with BnBr (85 ml, 0.72 mmol), stirred for 3.5 h, treated carefully with MeOH (0.3 ml), and diluted with AcOEt
(40 ml). The org. phase was separated, washed with H2O (3 Â 10 ml), dried (Na2SO4), and evaporated. FC (40 g
of silica gel; hexane/AcOEt 10 : 1) of the oily residue gave 5 (264 mg, 88%). Colourless oil. Rf (hexane/AcOEt
9 : 1) 0.20. [a]2D0 ˆ 20.1 (c ˆ 0.50, CHCl3). FT-IR (1.5%, CHCl3): 3089w, 3066m, 3008m, 2913m, 2865m, 1951w,
1876w, 1811w, 1711w, 1604w, 1496m, 1454m, 1361m, 1309w, 1140m, 1093s, 1067s, 1028m, 911w, 855w, 607w, 552w,
530w, 514w. 1H-NMR (300 MHz, C6D6): 7.42 ± 7.04 (25 arom. H); 5.90 (dd, J ˆ 10.3, 2.5, H C(5)); 5.76
(dd, J ˆ 10.3, 1.9, H C(6)); 5.07 (d, J ˆ 11.5, PhCH); 4.96 (d, J ˆ 11.5, PhCH); 4.89 (d, J ˆ 11.5, PhCH); 4.76 ±
4.64 (m, 3 PhCH); 4.61 (d, J ˆ 12.1, PhCH); 4.55 (d, J ˆ 12.1, PhCH); 4.49 (dd, J ˆ 10.6, 7.5, H C(3)); 4.23
(d, J ˆ 12.1, PhCH); 4.19 (dt, J ˆ 7.5, 2.2, H C(4)); 4.18 (d, J ˆ 12.1, PhCH); 3.97 (d, J ˆ 10.6, H C(2));
3.73 (d, J ˆ 8.7, CH C(1)); 3.53 (d, J ˆ 8.7, CH' C(1)). 13C-NMR (75 MHz, CDCl3): 140.33(s); 139.91(s);
139.15(s); 138.79(s); 138.16(s); 132.40 (d, C(5)); 129.72 (d, C(6)); 128.65 ± 127.44 (several d); 81.98(d);
80.73(d); 80.00(d); 78.13 (s, C(1)); 75.75(t); 75.30(t); 73.40(t); 72.13(t); 71.69(t); 66.84(t). FAB-MS (NOBA):
‡
‡
‡
625 (11, [M 1] ), 519 (18, [M BnO] ), 412 (25, [M BnO BnO] ), 321(17), 291(7), 271(19), 213(14),
197(20), 181(100). Anal. calc. for C42H42O5 (626.79): C 80.48, H 6.75; found: C 80.35, H 6.61.
(1d)-(1,3/2,4)-1,2,3-Tri-O-benzyl-4-C-[(benzyloxy)methyl]cyclohex-5-ene-1,2,3,4-tetrol (8) [44]. A soln. of
7 (22 mg, 0.04 mmol) in CH2Cl2 (5 ml) was degassed by puckering with N2, treated with 1 (10 mg, 0.012 mmol),
stirred at r.t. for 5 d, and evaporated. FC (5 g of silica gel; hexane/AcOEt 4 :1) of the residual oil gave 18 mg of a
green oil, which was subjected to an additional FC (as above) yielding 8 (14 mg, 66%). Colourless oil. Rf

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Helvetica Chimica Acta ± Vol. 82 (1999)
(hexane/AcOEt 3 :1) 0.31. [a]2D5 ˆ 8.7 (c ˆ 1.01, CHCl3; [44]: [a]D ˆ 8.5 (c ˆ 1, CHCl3)). FT-IR (1%, CHCl3):
3553m, 3089w, 3066w, 3007m, 2866m, 1951w, 1811w, 1603w, 1497m, 1454m, 1360m, 1329w, 1090s, 1069s, 1028m,
1
930w, 911w, 609w, 515w, 507w. H-NMR (300 MHz, CDCl3): see [44]. 13C-NMR (75 MHz, CDCl3): 138.79(s);
138.61(s); 138.34(s); 137.93(s); 131.93 (d, C(6)*); 128.42 ± 127.60 (several d); 126.59 (d, C(5)*); 83.97(d);
81.69(d); 79.68(d); 75.77 (s, C(4)); 75.69(t); 75.14(t); 73.99(t); 73.78(t); 73.13(t). FAB-MS (NOBA): 756(7),
‡
‡
‡
‡
663(11), 559 (15, [M ‡ Na] ), 535 (29, [M 1] ), 519 (100, [M OH] ), 429 (11, [M BnO] ), 412 (17,
‡
[M BnO OH] ), 321(14), 296(10), 271(12), 231(6), 213(8), 181(89).
(1d)-(1,3/2,4)-1,2,3,4-Tetra-O-benzyl-1-C-[(benzyloxy)methyl]cyclohex-5-ene-1,2,3,4-tetrol (9). A cooled
(08) soln. of 8 (7.5 mg, 14 mmol) in DMF (1.5 ml) was treated with NaH (60% suspension in oil, 5 mg, 125 mmol),
stirred for 30 min, treated with BnBr (30 ml, 250 mmol), allowed to warm to r.t., and stirred for 4 h. The mixture
was treated with MeOH (0.1 ml), diluted with AcOEt (20 ml), washed with H2O (2 Â 5 ml), brine (5 ml), dried
(Na2SO4), and evaporated. FC (10 g of silica gel, hexane/AcOEt 10 : 1) gave 9 (4.3 mg, 49%). Colourless oil. Rf
(hexane/AcOEt 9 : 1) 0.24. [a]2D0 ˆ 26 (c ˆ 0.2, CHCl3). 1H-NMR (300 MHz, C6D6): 7.42 ± 7.08 (25 arom. H);
5.84 (dd, J ˆ 10.6, 1.9, H C(5)); 5.67 (dd, J ˆ 10.6, 2.2, H C(6)); 5.04 (d, J ˆ 11.5, PhCH); 4.91 (d, J ˆ 11.5,
PhCH); 4.86 (s, PhCH2); 4.65 (d, J ˆ 12.1, PhCH); 4.59 (d, J ˆ 12.1, PhCH); 4.47 ± 4.38 (m, 2 PhCH, H C(3));
4.36 (d, J ˆ 11.8, PhCH); 4.27 (d, J ˆ 11.8, PhCH); 4.22 (dt, J ˆ 7.8, 2.2, H C(4)); 4.14 (d, J ˆ 9.7, CH C(1));
3.97 (d, J ˆ 10.3, H C(2)); 3.76 (d, J ˆ 9.7, CH' (1)).
(1d)-(1,3,4/2)-1,2,3-Tri-O-benzyl-4-C-[(benzyloxy)methyl]-4-O-carbamoylcyclohex-5-ene-1,2,3,4-tetrol (11).
A cooled (08) soln. of 4 (300 mg, 0.56 mmol) in CH2Cl2 (5 ml) was treated dropwise with CCl3CONCO (133 ml,
1.12 mmol), stirred for 30 min at this temp., and evaporated. The residue, dissolved in MeOH (10 ml) and H2O
(1 ml), was cooled to 08, treated with K2CO3 (0.24 g, 1.72 mmol), and stirred for 100 min at 08 and 100 min at r.t..
After evaporation of MeOH, the aq. soln. was diluted with H2O (10 ml) and extracted with CH2Cl2 (4 Â 15 ml).
The combined org. phases were washed with brine (10 ml), dried (MgSO4), and evaporated. FC (30 g of silica
gel, hexane/AcOEt 5 : 2) of the resulting oil (394 mg) gave 11 (281 mg, 86%). Colourless oil. Rf (hexane/AcOEt
2 : 1) 0.24. [a]2D5 ˆ 36.6 (c ˆ 0.50, CHCl3). FT-IR (0.5%, CHCl3): 3543m, 3428m, 3089w, 3066w, 3008m, 2939m,
2866m, 1952w, 1810w, 1729s, 1582s, 1497m, 1454m, 1357s, 1281w, 1175w, 1143m, 1091s, 1059s, 1028m, 930w, 911w,
1
629w, 606w, 554w. H-NMR (300 MHz, CDCl3): 7.38 ± 7.20 (m, 20 arom. H); 6.34 (dd, J ˆ 10.3, 1.9, H C(6));
5.95 (dd, J ˆ 10.3, 2.5, H C(5)); 4.91 (s, PhCH2); 4.90 (d, J ˆ 10.9, PhCH); 4.70 (s, PhCH2); 4.58 (d, J ˆ 10.9,
PhCH); 4.51 (d, J ˆ 12.1, PhCH); 4.40 (d, J ˆ 12.1, PhCH); 4.60 ± 4.49 (br., NH2); 4.23 (d, J ˆ 8.1, CH C(4));
4.22 (dt, J ˆ 7.2, 2.2, H C(1)); 4.16 (dd, J ˆ 10.0, 7.2, H C(2)); 3.90 (d, J ˆ 10.0, H C(3)); 3.85 (d, J ˆ 8.1,
CH' C(4)). 13C-NMR (75 MHz, CDCl3): 155.60 (s, CˆO); 139.12(s); 138.62(s); 138.52(s); 138.02(s);
131.58 (d, C(6)); 129.52 (d, C(5)); 128.72 ± 127.79 (several d); 81.56 (d, C(2)); 81.02 (s, C(4)); 80.55 (d, C(1));
‡
78.77 (d, C(3)); 76.17(t); 75.26(t); 73.61(t); 72.13(t); 69.02(t). FAB-MS (NOBA): 602 (11, [M ‡ Na] ),
‡
‡
‡
‡
580 (7, [M ‡ 1] ), 519 (59, [M NH2CO2] ), 472 (95, [M BnO] ), 411 (66, [M BnOH NH2CO2] ),
321(19), 213(23), 197(13), 181(100), 154(45), 136(34), 123(18), 107(19). Anal. calc. for C36H37NO6
(579.69): C 74.59, H 6.43, N 2.42; found: C 74.52, H 6.49, N 2.41.
(1l)-(1,3,4/2)-1,2,3-Tri-O-benzyl-4-[(benzyloxycarbonyl)amino]-6-[(benzyloxy)methyl]cyclohex-5-ene-
1,2,3-triol (14). A cooled ( 208) soln. of 11 (228 mg, 0.39 mmol), Ph3P (258 mg, 0.98 mmol) and Et3N (110 ml,
0.79 mmol) in CH2Cl2 (4.5 ml) was treated dropwise with a soln. of CBr4 (365 mg, 1.10 mmol) in CH2Cl2
(2.1 ml), stirred for 1 h at 208, treated dropwise with BnOH (326 ml, 3.15 mmol), and allowed to warm to r.t.
overnight. The mixture was poured into H2O (10 ml). The org. phase was separated and the aq. phase extracted
with CH2Cl2 (4 Â 10 ml). The combined org. phases were washed with brine (10 ml), dried (Na2SO4), and
evaporated. FC (35 g of silica gel; hexane/AcOEt 9 : 2) of the resulting oil (1.4 g) gave a mixture of 14 and
BnOH. Removal of BnOH in h.v. at 608 gave pure 14 (184 mg, 70%). Colourless oil. Rf (hexane/AcOEt 3 : 1)
0.43. [a]2D5 ˆ 30.9 (c ˆ 1.51, CHCl3). FT-IR (1.5%, CHCl3): 3439m, 3089w, 3067m, 3008m, 2865m, 1952w, 1876w,
1810w, 1717s, 1604w, 1498s, 1454m, 1366w, 1331m, 1294m, 1144m, 1068s, 1028m, 911w, 604w, 544w, 536w,
520w. 1H-NMR (300 MHz, CDCl3): 7.38 ± 7.23 (m, 25 arom. H); 5.81 (br. d, J ˆ 3.1,
H C(5)); 5.11
(s, PhCH2OCˆO); 5.07 (d, J ˆ 9.7, NH); 4.77 ± 4.63 (m, 2 PhCH, H C(4)); 4.60 (s, PhCH2); 4.59 (d, J ˆ 11.2,
PhCH); 4.57 (d, J ˆ 11.5, PhCH); 4.49 (d, J ˆ 11.8, PhCH); 4.40 (d, J ˆ 11.8, PhCH); 4.24 (d, J ˆ 12.1,
CH C(6)); 4.05 (br. d, J ˆ 4.3,
H
C(1)); 3.90 (d, J ˆ 12.1, CH' C(6)); 3.81 (dd, J ˆ 7.5, 4.7,
H C(3));
3.73 (br. dd, J ˆ 7.5, 4.3, H C(2)). 13C-NMR (75 MHz, CDCl3): 156.41 (s, CˆO); 138.50(s); 138.41(s);
138.12(s); 137.35(s); 136.80(s); 1s hidden by noise or other signals; 128.76 ± 127.87 (several d); 125.40
(d, C(5)); 77.26(d); 76.33(d); 75.96(d); 74.42(t); 73.84(t); 72.30(t); 72.13(t); 70.62 (t, CH2 C(6)); 66.92
‡
‡
(t, COOCH2Ph); 47.20 (d, C(4)). FAB-MS (NOBA): 670 (9, [M ‡ 1] ), 562 (100, [M BnO] ), 534(6),
‡
518 (7, [M BnOCO2] ), 472(9), 429(12), 181(33). Anal. calc. for C43H43NO6 (669.82): C 77.11, H 6.47,
N 2.09; found: C 77.10, H 6.25, N 2.09.

Helvetica Chimica Acta ± Vol. 82 (1999)
653
(1l)-(1,3,4/2)-4-Acetamido-1,2,3-tri-O-benzyl-6-[(benzyloxy)methyl]cyclohex-5-ene-1,2,3-triol (15) [32]. A
cooled ( 208) soln. of 11 (260 mg, 0.45 mmol), Ph3P (296 mg, 1.13 mmol) and Et3N (126 ml, 0.90 mmol) in
CH2Cl2 (5 ml) was treated dropwise with a soln. of CBr4 (420 mg, 1.27 mmol) in CH2Cl2 (2.4 ml), stirred for 1 h
at this temp., and treated dropwise with 2.0m Me3Al in heptane (1.8 ml, 3.62 mmol). After stirring for 1 h at
208, the mixture was treated carefully with MeOH (2 ml), CH2Cl2 (5 ml), and 0.2m HCl (10 ml), and allowed
to warm to 08. The org. phase was separated and the aq. phase extracted with CH2Cl2 (6 Â 10 ml). The combined
organic phases were washed with brine (10 ml), dried (MgSO4), and evaporated. FC (30 g of silica gel; hexane/
AcOEt 1:1) of the resulting oil (1.1 g) gave 15 (200 mg, 77%). Colourless oil. Rf (hexane/AcOEt 1:1) 0.21.
[a]2D3 ˆ 23.4 (c ˆ 1.01, CHCl3; [32]: [a]2D3 ˆ 22 (c ˆ 1, CHCl3)). FT-IR (0.6%, CHCl3): 3438m, 3065w, 3008m,
2976m, 2895m, 1667m, 1603w, 1498m, 1454m, 1390m, 1370m, 1297w, 1146w, 1048s, 877m, 847w, 600w, 522w,
506w. 1H-NMR (300 MHz, CDCl3): 7.36 ± 7.25 (m, 20 arom. H); 5.76 (d, J ˆ 3.7, H C(5)); 5.69 (d, J ˆ 9.0,
NH); 4.96 ± 4.93 (m, H C(4)); 4.74 (d, J ˆ 11.5, PhCH); 4.70 (d, J ˆ 10.3, PhCH); 4.62 (d, J ˆ 11.2, PhCH);
4.60 (d, J ˆ 12.1, PhCH); 4.58 (d, J ˆ 11.5, PhCH); 4.54 (d, J ˆ 11.5, PhCH); 4.49 (d, J ˆ 12.1, PhCH); 4.40
(d, J ˆ 11.8, PhCH); 4.27 (d, J ˆ 12.1, CH C(6)); 4.07 (br. d, J ˆ 4.1, H C(1)); 3.90 (d, J ˆ 12.1, CH' C(6));
3.82 (dd, J ˆ 7.2, 4.1, H C(2)); 3.73 (dd, J ˆ 7.2, 4.7, H C(3)); 1.93 (s, Ac). 13C-NMR (75 MHz, CDCl3):
169.92 (s, CˆO); 138.49(s); 138.45(s); 138.41(s); 138.07(s); 137.01 (s, C(6)); 128.73 ± 127.86 (several d);
125.61 (d, C(5)); 76.91(d); 75.94(d), 75.62(d); 74.50(t); 73.65(t); 72.16(t); 72.04(t); 70.67 (t, CH2 C(6));
‡
‡
45.19 (d, C(4)); 23.49 (q, Me). FAB-MS (NOBA): 1155 (8, [2M ‡ 1] ), 600 (11, [M ‡ Na] ), 578 (98, [M ‡
‡
‡
1] ), 471 (100, [M ‡ 1 BnO] ), 380(46), 363(20), 337(20), 272(16), 254(41), 242(11), 228(19), 212(32),
181(87), 164(61), 154(75), 150(42), 138(58), 136(74), 107(23).
(1l)-(1,3,4/2)-4-Amino-6-(hydroxymethyl)cyclohex-5-ene-1,2,3-triol ((‡)-Valienamine, 16) [39][45][66] and
(1l)-(1,3,4/2)-4-Acetamido-1,2,3-tri-O-acetyl-6-[(acetyloxy)methyl]cyclohex-5-ene-1,2,3-triol (17) [35][37][44]. At
788, NH3 (20 ml) was condensed into a soln. of 14 (145 mg, 0.22 mmol) in THF (5 ml). The soln. was treated
with Na in small pieces (ca. 30 mg), until the blue colour of the soln. persisted. After stirring for 2 h at 788, the
mixture was treated with NH4Cl (220 mg), stirred at r.t. overnight, and evaporated. The residue was dried in
h.v., extracted with abs. MeOH, filtered, and evaporated. The resulting residue was extracted with EtOH,
filtered, and evaporated. The residue (66 mg) was adsorbed on 3 ml of neutral Dowex 50-WX-8 (washed with
H2O). After washing with H2O (30 ml), elution with 2% aq. NH3 gave 16 (30 mg, 78%). Slightly yellow solid.
1
[a]2D5 ˆ 79.3 (c ˆ 1.5, H2O; [66]: [a]2D5 ˆ 81.6 (H2O)). H-NMR (300 MHz, D2O): see [45]. 13C-NMR (75 MHz,
D2O): see [66]. Conventional acetylation of 16 gave, after FC, 17 (55 mg, 86%). Colourless crystals (Et2O). Rf
(toluene/acetone 7:2) 0.08. M.p. 94 ± 958 ([35]: 92.5 ± 958 (EtOH/toluene)). [a]2D5 ˆ 26.3 (c ˆ 1.02, CHCl3; [44]:
[a]D ˆ 24 (c ˆ 1, CHCl3)). 1H-(300 MHz, CDCl3) and 13C-NMR (75 MHz, CDCl3): see [37]. FAB-MS (NOBA):
‡
‡
‡
771 (21, [2M ‡ 1] ), 386 (41, [M ‡ 1] ), 326 (100, [M AcO] ), 284(7), 206(7), 164(12), 122(12).
1,3,4,5-Tetra-O-benzyl-6,7-dideoxy-d-arabino-hept-6-en-2-ulose (19). A soln. of 18 [67] (1.86 g, 3.45 mmol)
in toluene (6.7 ml) was treated with dicyclohexyl carbodiimide (1.67 g, 8.09 mmol), DMSO (0.93 ml,
17.60 mmol), and pyridine (0.37 ml, 4.58 mmol), and then dropwise with CF3COOH (0.37 ml, 3.32 mmol),
and stirred for 4 h. The mixture was treated with H2O (2 ml), Et2O (9.5 ml), and filtered through Celite. The
filter residue was washed with Et2O (25 ml). The filtrate was washed with 1m HCl (2 Â 10 ml), sat. aq. NaHCO3
soln. (20 ml), and brine (20 ml), dried (Na2SO4), and evaporated. FC (110 g of silica gel; hexane/AcOEt 6 : 1)
of the residue (2.6 g) gave 19 (1.58 g, 87%). Colourless oil. Rf (hexane/AcOEt 3 : 1) 0.59. [a]D25
ˆ
39.8 (c ˆ 1.52,
CHCl3). FT-IR (1.5%, CHCl3): 3089m, 3067m, 3008m, 2868m, 1952w, 1874w, 1811w, 1728s, 1604w, 1497m,
1454m, 1422w, 1391w, 1336w, 1306w, 1171w, 1072s, 1028m, 996m, 936m, 908w, 818w, 651w, 601w, 538w, 520w.
1H-NMR (300 MHz, CDCl3): 7.35 ± 7.16 (20 arom. H); 5.89 (ddd, J ˆ 17.4, 10.3, 7.8, H C(6)); 5.50 ± 5.41
(m, 2 H C(7)); 4.61 ± 4.55 (m, 2 H); 4.48 ± 4.29 (m, 7 H); 4.23 ± 4.17 (m, 2 H); 4.08 (br. t, J ˆ 8.1, H C(5));
3.92 (dd, J ˆ 8.4, 3.4, H C(4)). 13C-NMR (75 MHz, CDCl3): 209.33 (s, C(2)); 138.34(s); 137.82(s); 137.63(s);
137.29(s); 136.17 (d, C(6)); 128.75 ± 127.84 (several d); 120.69 (t, C(7)); 84.37(d); 82.56(d); 79.60(d); 75.09(t);
‡
‡
74.71(t); 74.55(t); 73.37(t); 70.17(t). FAB-MS (NOBA): 559 (86, [M ‡ Na] ), 537 (43, [M ‡ 1] ), 536
‡
‡
‡
(36, [M] ), 535 (26, [M 1] ), 429 (96, [M BnO] ), 271(31), 181(100). Anal. calc. for C35H36O5 (536.67):
C 78.33, H 6.76; found: C 78.29, H 6.75.
3,4,5-Tri-O-benzyl-6-C-[(benzyloxy)methyl]-1,2,7,8-tetradeoxy-d-manno-octa-1,7-dienitol (20). A cooled
(
788) soln. of 19 (1.49 g, 2.77 mmol) in THF (31 ml) was treated dropwise with 1m vinylmagnesium bromide
in THF (4.15 ml, 4.15 mmol), stirred for 85 min, treated with Et2O (40 ml), warmed to 08, and treated with sat.
aq. NH4Cl soln. (40 ml). The org. phase was separated and the aq. phase extracted with Et2O (2 Â 20 ml). The
combined org. phases were washed with brine (30 ml), dried (Na2SO4), and evaporated. FC (110 g of silica gel;
hexane/AcOEt 6.5 : 1) of the oily residue (1.85 g) gave 20 (1.49 g, 95%). Colourless oil. Rf (hexane/AcOEt 3 : 1)
0.64. [a]2D5
ˆ
4.5 (c ˆ 1.5, CHCl3). FT-IR (1.5%, CHCl3): 3462m, 3089m, 3066m, 3008m, 2909m, 1951w, 1870w,

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Helvetica Chimica Acta ± Vol. 82 (1999)
1810w, 1749w, 1700w, 1637w, 1605w, 1558w, 1497m, 1454m, 1420w, 1397m, 1348m, 1307w, 1091s, 1028s, 1000m,
1
934m, 634w, 602w, 580w, 564w, 550w, 544w, 534w. H-NMR (300 MHz, CDCl3): 7.36 ± 7.22 (20 arom. H); 6.18
(dd, J ˆ 17.4, 10.9,
C(1)); 5.26 (dd, J ˆ 10.9, 1.9, H' C(8)); 4.71 (d, J ˆ 10.6, PhCH); 4.72 ± 4.52 (m, 4 PhCH); 4.49 (d, J ˆ
11.8, PhCH); 4.43 (d, J ˆ 12.1, PhCH); 4.24 (d, J ˆ 11.8, PhCH); 4.07 (d, J ˆ 2.5, H C(5)); 4.05 (br. t, J ˆ 7.5,
H
C(7)); 6.02 ± 5.91 (m, H C(2)); 5.56 (dd, J ˆ 17.4, 1.9,
H C(8)); 5.47 ± 5.42 (m, 2
H
H
C(3)); 3.90 (dd, J ˆ 7.2, 2.5, H C(4)); 3.75 (s, OH); 3.73 (d, J ˆ 8.7, CH C(6)); 3.28 (d, J ˆ 8.7, CH' C(6)).
13C-NMR (75 MHz, CDCl3): 140.72 (d, C(7)); 138.97(s); 138.55(s); 138.49(s); 138.34(s); 136.35 (d, C(2));
128.63 ± 127.63 (several d); 120.22 (t, C(1)); 114.87 (t, C(8)); 81.46(d); 81.04(d); 78.56(d); 78.05 (s, C(6));
‡
‡
75.09(t); 74.97(t); 73.61(t); 73.37(t); 70.05(t). FAB-MS (NOBA): 1129 (3, [2M ‡ 1] ), 587 (8, [M ‡ Na] ),
‡
‡
565 (100, [M ‡ 1] ), 457 (27, [M BnO] ), 181(15). Anal. calc. for C37H40O5 (564.72): C 78.70, H 7.14; found:
C 78.60, H 7.12.
(1l)-(1,2/3,4)-1,2,3-Tri-O-benzyl-4-C-[(benzyloxy)methyl]cyclohex-5-ene-1,2,3,4-tetrol (21). A soln. of 20
(2.20 g, 3.89 mmol) in CH2Cl2 (200 ml, degassed by puckering with N2) was treated with 1 (480 mg, 0.58 mmol),
stirred for 4 d under N2, and concentrated. FC (250 g of silica gel; hexane/AcOEt 4 :1) of the oily residue gave 21
(1.85 g, 89%). Green oil. Rf (cyclohexane/AcOEt 3:1) 0.44. [a]D25
ˆ
35.2 (c ˆ 1.5, CHCl3). FT-IR (1.5%,
CHCl3): 3532m, 3089m, 3066m, 3008m, 2864m, 1951w, 1877w, 1811w, 1737w, 1604w, 1496m, 1454m, 1368m,
1306m, 1098s, 1028m, 913w, 855w, 636w, 601w, 563w, 536w, 524w. 1H-NMR (300 MHz, CDCl3): 7.41 ± 7.22
(20 arom. H); 5.95 (dd, J ˆ 10.0, 5.0, H C(6)); 5.79 (d, J ˆ 10.0, irrad. at 3.45 ! NOE of 5%, H C(5));
4.97 (d, J ˆ 10.9, PhCH); 4.77 (d, J ˆ 12.1, PhCH); 4.75 ± 4.67 (m, 3 PhCH); 4.59 (d, J ˆ 10.9, PhCH); 4.57
(d, J ˆ 12.1, PhCH); 4.46 (d, J ˆ 12.1, PhCH); 4.26 (d, J ˆ 9.7, irrad. at 3.45 ! NOE of 10%, H C(3));
4.16 (dd, J ˆ 5.0, 3.7, irrad. at 5.95 ! NOE of 15%, H C(1)); 3.94 (dd, J ˆ 9.7, 3.7, H (2)); 3.46 (d, J ˆ 9.3,
CH C(4)); 3.43 (d, J ˆ 9.3, CH' C(4)); 3.10 (s, OH). 13C-NMR (75 MHz, CDCl3): 139.10(s); 138.88(s);
138.52(s); 138.39(s); 132.84 (br. d, C(5)); 128.59 ± 127.81 (several d, incl. C(6)); 78.16 (d, C(2)); 75.98
(d, C(3)); 75.57(t); 74.55 (t, CH2 C(4)); 73.58(t); 73.08 (s, C(4)); 72.87(t); 71.88(t); 71.69 (d, C(1)). Anal.
calc. for C35H36O5 (536.67): C 78.33, H 6.76; found: C 78.42, H 6.87.
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Received March 13, 1999