Preliminary studies on the synthesis of rancinamycins from nitrosugars: First total synthesis of (3S,4S,5S,6R)-5-benzyloxy-6-hydroxy-3,4- (isopropylidendioxy)-cyclohex-1-enecarbaldehyde

Article abstract of DOI:10.1016/j.tetasy.2005.10.044

The first total synthesis of (3S,4S,5S,6R)-5-benzyloxy-6-hydroxy-3,4- (isopropylidendioxy)-cyclohex-1-enecarbaldehyde from d-glucose is described. The key steps of this synthesis are the stereoselective Michael addition of 2-lithio-1,3-dithiane to 3-O-ben

Full text of DOI:10.1016/j.tetasy.2005.10.044

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 4045–4049
Preliminary studies on the synthesis of rancinamycins from
nitrosugars: first total synthesis of (3S,4S,5S,6R)-5-benzyloxy-
6-hydroxy-3,4-(isopropylidendioxy)-cyclohex-1-enecarbaldehyde
*
´
´
´
´
´
Jose M. Otero, Fernando Fernandez, Juan C. Estevez and Ramon J. Estevez
Departamento de Quı´mica Orga´nica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Received 8 October 2005; accepted 14 October 2005
Abstract—The first total synthesis of (3S,4S,5S,6R)-5-benzyloxy-6-hydroxy-3,4-(isopropylidendioxy)-cyclohex-1-enecarbaldehyde
from D-glucose is described. The key steps of this synthesis are the stereoselective Michael addition of 2-lithio-1,3-dithiane to
3-O-benzyl-5,6-dideoxy-1,2-O-isopropylidene-6-nitro-a-D-xilo-hex-5-enofuranose followed by the enantioselective two-step trans-
formation of 3-O-benzyl-5,6-dideoxy-5-C-(1,3-dithian-2-yl)-6-nitro-b-L-idofuranose into (1S,2S,3S,4S,5S,6R)-5-benzyloxy-6-
hydroxy-3,4-(isopropylidendioxy)-2-nitro-cyclohexanecarbaldehyde propylene dithioacetal, which was finally converted into the
target compound.
ꢀ 2005 Elsevier Ltd. All rights reserved.
OH
1. Introduction
RO
O
1
a) R=COi-Pr
b) R1=COn-Pr
c) R1=COn-Bu
d) R=H
OH
OH
Carbasugars are a family of polyhydroxylated cyclo-
pentanes and cyclohexanes, structurally similar to that
of cyclic monosaccharides, from which they can for-
mally be derived by replacement of the ring oxygen
atom with a methylene group.1 Due to the lack of an
easily hydrolysable glycosidic function, these sugar
derivatives are stable towards hydrolysis. Additionally,
as they are topologically similar to that of normal sug-
ars, particularly in the arrangement of their hydroxy
groups, they can mimic sugars in biological systems
and thus may act as enzyme inhibitors and have been
used as sweeteners, antibiotics and anticancer agents.2
H
Figure 1.
As they have a wide range of pharmacological applica-
tions, carbasugars are receiving considerable attention
from chemists and biochemists. Much attention has
been devoted to the development of regio- and stereo-
selective synthetic methodologies for their preparation,
most of which are based on the conversion of sugars into
carbocycles.5 Several approaches have been developed
for the transformation of sugars into enantiomerically
pure carbasugars,5a including the intramolecular nitro-
aldol condensation (Henry reaction),6 which has proven
to be a powerful method for the preparation of nitro-
cycloalkanes, that has recently been used by us for the
preparation of cyclohexane a-amino acids, cyclopentane
b-amino acids, dehydrohydroxymethylinositols, among
other carbasugars.7
The use of the term carbasugar has also been extended
to closely related compounds,3 including unsaturated
carbasugars such as rancimamycin III 1d, a member of
a group of secondary metabolites known as rancinamyc-
ins 1a–d,4 which are produced by Streptomyces lincoln-
ensis in a sulfur-depleted culture medium and have
important antibiotic activity in vitro against Proteus vul-
garis, Proteus rettgeri and Staphylococcus aureus
(Fig. 1).
Herein we describe the first total synthesis of a rancina-
mycin analogue 1e from nitrosugars,8 following a route
which includes an improvement of the previously
described9 transformation of nitrosugar 4b into cyclitol
*
Corresponding author. Tel.: +34 981 563100; fax: +34 981 591014;
e-mail: qorjec@usc.es
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.10.044

4046
J. M. Otero et al. / Tetrahedron: Asymmetry 16 (2005) 4045–4049
O2N
O2N
S
O2N
S
O
several
steps
O
O
O
O
O
i
O
O
O
O
S
S
See ref. 10
O
O
O
O
HO
BnO
HO
BnO
BnO
3
4a
4b
2
OBn
OH
OBn
NO2
OBn
OBn
NO2
OBn
1e
HO
OH
OH
HO
O
ii
iv
HO
v
O
O
4b
S
S
S
O
OH
H
S
NO2
S
S
NO2
6b
O
5b
7
5a
iii
OBn
OBn
HO
HO
O
O
O
HO
O
O
S
S
O
H
S
NO2
S
NO2
O
6a
6b
Scheme 1. Reagents and conditions: (i) 2-lithio-1,3-dithiane, THF, ꢀ78 ꢁC, 2 h, (4a:4b—1:3), 78% yield; (ii) (a) AcOH (aq) (75%), reflux, 3 h; (b)
NaHCO3 (aq) (2%), MeOH, rt, 12 h, (5a:5b—1:2.5), 87% yield; (iii) CH3OC(CH3)CH2, PPTS, CH2Cl2, reflux, 3 h, 24% yield of 6a, 61% yield of 6b;
(iv) (CH3O)2C(CH3)2, PTSA, acetone, rt, 12 h, 87% yield; (v) MeI, NaHCO3 (aq), CH3CN, 35 ꢁC, 36 h, 53% yield.
6b prior to a new way of removing nitro groups from
nitrocarbasugars (Scheme 1).
improve on a previous similar experiment carried out
at ꢀ45 ꢁC, in which there were a 60% global yield and
a 3:4 ratio of 4a and 4b, and the configuration of both
epimers was indirectly established.9
2. Results and discussion
The next step was the removal of the 1,2-O-isopropylid-
ene group of the major component 4b with acetic acid.
The resulting free sugar was directly treated with
2.5 equiv of sodium hydrogen carbonate in aqueous
methanol at room temperature for 12 h, giving a 87%
yield of an unisolable syrupy mixture of 5a and 5b
(TLC). Refluxing of a solution of this mixture with 2-
methoxypropene and PPTS in methylene chloride for
3 h allowed isopropylidene nitrocyclohexanes 6a (not
previously described) and 6b12 to be isolated from the
reaction mixture in 24% and 61% yields, respectively.
Nitro-olefin 310 obtained from diacetone-D-glucose 2
was allowed to react with 1.2 equiv of 2-lithio-1,3-dithi-
ane at ꢀ78 ꢁC for 2 h, the result being a 78% yield of a
1:3 mixture for compounds 4a and 4b, a ratio estab-
lished by NMR (comparison of the intensity of H1 pro-
tons). The major component 4b was easily isolated by
crystallization and its structure unambiguously estab-
lished by means of an X-ray experiment (Fig. 2).11 The
above stereoselectivity is due to the presence of a benzyl-
oxy group at position C3, which means that attack by
the dithiane anion on the double bound face leading
to the minor component 4a is difficult. These results
The myo configuration assigned to the previously
uncharacterized inositol derivative 6b was easily estab-
lished by taking into account that configurations of ste-
reogenic centres of C1, C4, C5 and C6 are the same as
those of its precursor 4b and presupposing that this
compound predominately adopts the thermodynami-
cally preferred chair-like conformation 6b (Scheme 2)
where H3 adopts an equatorial disposition and the rest
of the hydrogens on the ring adopt axial dispositions.
1
This was easily confirmed from its H NMR spectrum,
since all the coupling constants of the ring protons were
7.5–10 Hz, except for coupling constants of H2 and H3
(J2,3 = 4.3 Hz) and H3 and H4 (J3,4 = 7.0 Hz). The scyllo
configuration of the new minor inositol derivative 6a
was also established from its 1H NMR data, which
revealed that H1, H2, H3, H4, H5 and H6 are all axial
(Scheme 2).
The formation of compounds 6a and 6b can be explai-
ned as indicated in Scheme 2. The intramolecular Henry
reaction in the open form 8b of nitrosugar 8a gives a
Figure 2. An ORTEP diagram corresponding to the X-ray molecular
structure of compound 4b.

J. M. Otero et al. / Tetrahedron: Asymmetry 16 (2005) 4045–4049
4047
NO2
BnO
BnO
HO
O2N
HO
O2N
OR1
H
H
O
OH
NTD
NTD
OR2
OR2
NTD
OR1
6a
6b
8a
H
BnO
OH
H
OBn
BnO
BnO
BnO
BnO
HO
O2N
HO
O2N
HO
O2N
HO
O2N
O
HO
H
H
OH
H
OH
NTD
NTD
NTD
NTD
OH
OH
OH
OH
O
H
H
HO
O
NTD
8b
5a
5b
9a
9b
H
H
H
H
NO2
S
Scheme 2. R1 + R2 = –CMe2 NTD = HC
.
S
mixture of nitrocyclohexanes 5a and 5b via chair transi-
tion states of the corresponding nitronates 9a and 9b,
each having an equatorial nitro group. Compounds 5a
and 5b can easily revert to compound 8b by a retro-
Henry reaction. As compound 5a is thermodynamically
more stable than 5b, at the point of equilibrium 5a
should be more favoured with respect to 5b. Notwith-
standing, as stated previously, myo-inositol 5b is the pre-
dominant component in the mixture resulting from the
cyclization of compound 8b. Accordingly, the highly
remarkable stereoselectivity of this cyclization can be
explained by assuming that the formation of 5b is kineti-
cally favoured, and consequently that the acyclic
conformation 9b is more favoured than 9a.
determination of the stereochemistries of all its 14
described isomers. Additionally, we are exploring the
broad synthetic potential of this route for the prepara-
tion of other cyclohexane derivatives, including poly-
hydroxylated cyclohexane b-amino acids, carbasugars
and shikimic acid derivatives.
4. Experimental
Melting points were determined using a Kofler Thermo-
gerate apparatus and are uncorrected. Specific rotations
were recorded on a JASCO DIP-370 optical polari-
meter. Infrared spectra were recorded on a MIDAC
Prospect-IR spectrophotometer. Nuclear magnetic
resonance spectra were recorded on a Bruker DPX-250
apparatus. Mass spectra were obtained on a Hewlett
Packard 5988A mass spectrometer. Elemental analyses
were obtained from the Elemental Analysis Service at
the University of Santiago de Compostela. Thin layer
chromatography (TLC) was performed using Merck
GF-254 type 60 silica gel and ethyl acetate/hexane mix-
tures as eluants; the TLC spots were visualized with
Hanessian mixture. Column chromatography was car-
ried out using Merck type 9385 silica gel. Solvents were
purified as per Ref. 14. Solutions of extracts in organic
solvents were dried with anhydrous sodium sulfate.
When the direct acetonization of the mixture 5a and 5b
was carried out in acetone at rt, surprisingly only com-
pound 6b was obtained. This enantioselectivity can be
explained as follows: the moderate reaction conditions
now used make the selective acetonization of inositol
5b possible due to the cis-configuration of the OH
groups at C3 and C4. This process is accompanied by
the displacement of the equilibrium between compounds
5a and 5b to 5b.
Finally, treatment of compound 6b with MeI and aque-
ous hydrogen sodium carbonate produced compound
1e, which was easily identified from its analytical and
spectroscopic data. Formation of this compound is
probably the result of the liberation of the masked car-
bonyl group of 6b followed by a kinetically and thermo-
dynamically favoured E1cB elimination of the nitro
group of the resulting b-nitro cyclohexanecarbaldehyde
7 in the basic reaction conditions.13
4.1. 3-O-Benzyl-5,6-dideoxy-5-C-(1,3-dithian-2-yl)-1,2-
O-isopropylidene-6-nitro-b-L-idofuranonse 4b
A 1.6 M solution of n-butyllithium in dry THF (6.8 mL,
10.81 mmol) was added dropwise under argon to a solu-
tion of 1,3-dithiane (1.36 g, 11.28 mmol) in dry THF
(60 mL) cooled to ꢀ78 ꢁC. After the addition, the reac-
tion mixture was stirred at ꢀ78 ꢁC for 1 h and then a
solution of 3-O-benzyl-5,6-dideoxy-1,2-O-isopropylid-
ene-6-nitro-a-D-xylo-hex-5-enofuranose 3 (3.02 g, 9.40
mmol) in dry THF (14 mL) was added dropwise
and the new reaction mixture was stirred for 2 h. After
aqueous ammonium chloride saturated solution
(50 mL) was added, the aqueous layer was extracted
with methylene chloride (3 · 50 mL) and the pooled
organic layers were dried with anhydrous sodium sul-
fate, filtered and concentrated in vacuo. The resulting
crude syrup was washed three times with hot hexane
and then methanol was added to deposit 3-O-benzyl-
3. Conclusion
In conclusion, we have developed the first total synthesis
of a rancinamycin-like compound from nitrosugars fol-
lowing a route, which includes the enantioselective
transformation of nitrosugar 4b into carbasugar deriva-
tive 6b.
Work is currently in progress to extend this route to the
panel of hexoses in order to prepare a wide range of
rancinamicyns 1 for chemical and biological studies,

4048
J. M. Otero et al. / Tetrahedron: Asymmetry 16 (2005) 4045–4049
5,6-dideoxy-5-C-(dithian-2-yl)-1,2-O-isopropylidene-6-
nitro-b-L-idofuranose 4b (2.32 g, 5.26 mmol, 56%
yield) as a white solid. Crystallization from ethyl
d = 25.7; 26.5; 26.8; 31.6; 31.9; 48.0; 49.6; 72.2; 73.0;
77.2; 78.1; 80.2; 84.0; 113.4; 127.9; 128.0; 128.4; 137.7.
MS (CI): m/z (%) = 442 (100, MH+); 384 (45,
MH+ꢀC3H6O). IR (KBr, cmꢀ1): 3510 (OH); 1557, 1372
(NO2). Found: C, 54.60; H, 6.22; N, 3.16; S, 14.27.
C20H27NO6S2 requires C, 54.40; H, 6.16; N, 3.17; S, 14.52.
ether/hexane provided colourless crystals, mp 155–
20
157 ꢁC. ½aꢁ ¼ ꢀ35:0 (c 1.75 in CHCl3). 1H NMR
(CDCl3): dD= 1.33 (s, 3H, CH3); 1.52 (s, 3H, CH3);
1.80–1.95 (m, 1H, HC-CH2S); 2.00–2.13 (m, 1H, HC-
CH2S); 2.71–2.91 (m, 4H, 2 · CH2-S); 3.42–3.51 (m,
1H, H5); 4.03 (d, 1H, J3,4 = 3.1 Hz, H3); 4.17 (d, 1H,
J5,7 = 6.2 Hz, S-CH-S); 4.43 (d, 1H, Jgem = 11.4 Hz,
CH2Ph); 4.53–4.61 (m, 4H, H2 + H4 + H6 + CH2Ph);
20
1
Compound 6b: ½aꢁD ¼ ꢀ60:5 (c 3.75, CHCl3). H NMR
(CDCl3): d = 1.31 (s, 3H, CH3); 1.50 (s, 3H, CH3); 1.80–
1.91 (m, 1H, HC-CH2S); 2.07–2.15 (m, 1H, HC-CH2S);
2.81–3.01 (m, 6H, 2 · CH2-S + H1 + OH); 3.90 (t, 1H,
J4,5 = 4.3 Hz, J5,6 = 4.3 Hz, H5); 4.24–4.29 (m, 1H,
0
0
0
4.74 (dd, 1H, J5;6 ¼ 5:2 Hz, J6;6 ¼ 14:5 Hz, H6 ); 5.90
(d, 1H, J1,2 = 3.6 Hz, H1); 7.28–7.42 (m, 5H, 5 ·
Ar-H). 13C NMR (CDCl3): d = 25.3, 26.2; 26.7; 29.3;
29.4; 41.3; 46.9; 71.2; 74.1; 78.0; 81.3; 81.5; 104.2;
111.8; 128.0; 128.4; 136.6. MS (CI): m/z (%) = 442 (36,
MH+); 244 (100); 197 (45). IR (KBr, cmꢀ1): 1552,
1382 (NO2). Found: C, 54.42; H, 6.20; N, 3.27; S,
14.39. C20H27NO6S2 requires C, 54.40; H, 6.16; N,
3.17; S, 14.52.
0
H6); 4.50 (d, 1H, J1;1 ¼ 3:1 Hz, S-CH-S); 4.53 (ddd,
1H, J4,6 = 1.2 Hz, J4,5 = 4.3 Hz, J3,4 = 7.0 Hz, H4);
4.60 (d, 1H, Jgem = 11.7 Hz, CH2Ph); 4.81 (dd, 1H,
J2,3 = 4.3 Hz, J3,4 = 7.0 Hz, H3); 4.83 (d, 1H,
Jgem = 11.7 Hz, CH2Ph); 5.27 (dd, 1H, J2,3 = 4.3 Hz,
J1,2 = 10.9 Hz, H2); 7.29–7.38 (m, 5H, 5 · Ar-H). 13C
NMR (CDCl3): d = 23.7; 25.7; 25.9; 30.4; 31.1; 45.2;
49.7; 68.0; 72.4; 73.8; 76.4; 76.5; 81.9; 110.9; 127.9;
128.0; 128.4; 137.1. MS (CI): m/z (%) = 442 (100,
MH+); 384 (16, MH+ꢀC3H6O). IR (KBr, cmꢀ1): 3529
(OH); 1557, 1382 (NO2). Found: C, 54.82; H, 6.34; N,
3.03; S, 14.10. C20H27NO6S2 requires C, 54.40; H,
6.16; N, 3.17; S, 14.52.
4.2. Conversion of 4b into (1S,2S,3R,4S,5S,6R)-5-benz-
yloxy-6-hydroxy-3,4-(isopropylidendioxy)-2-nitro-cyclo-
hexanecarbaldehyde propylene dithioacetal 6a and
(1S,2S,3S,4S,5S,6R)-5-benzyloxy-6-hydroxy-3,4-(iso-
propylidendioxy)-2-nitro-cyclohexanecarbaldehyde
propylene dithioacetal 6b
4.2.2. Conversion of 5a and 5b into 6b. A mixture of 5a
and 5b, 2,2-dimethoxypropane (0.07 M), acetone
(0.1 M) and PTSA (0.2 equiv) and anhydrous copper
sulfate was stirred at rt for 12 h. The work-up furnished
a syrup that was subjected to flash column chromato-
graphy (ethyl acetate/hexane 1:3) giving an 87% yield
of myo-inositol 6b as a white foam.
A solution of 4b (0.43 g, 0.98 mmol) in 75% aqueous
acetic acid solution (25 mL) was refluxed for 3 h and
then the solvent was evaporated to dryness and coevap-
orated with toluene (3 · 10 mL). After the solid residue
was dissolved in methanol (30 mL), a 2% aqueous
sodium bicarbonate solution was added (10 mL, 2.44
mmol). This mixture was stirred overnight, and then
acidified with DOWEXꢂ 50 WX4-50, filtered and con-
centrated in vacuo to a syrup that was submitted to flash
column chromatography (ethyl acetate/hexane 1:1.5) to
isolate an 87% yield of a 1:2.5 mixture of 5a and 5b
(0.34 g, 0.85 mmol).
4.3. (3S,4S,5S,6R)-5-Benzyloxy-6-hydroxy-3,4-(isoprop-
ylidendioxy)-cyclohex-1-enecarbaldehyde 1e
Iodomethane (10 equiv) was added to a 0.1 M solution
of 6b and saturated aqueous sodium bicarbonate solu-
tion (0.5 M) in acetonitrile, and the mixture was heated
to 35 ꢁC for 36 h. The liquids were removed in vacuo
and the solid residue subjected to flash column chroma-
4.2.1. Conversion of 5a and 5b into 6a and 6b. A 0.8 M
solution of the above mixture of nitrocyclohexanes 5a
and 5b, 2-methoxypropene (30 equiv) and a catalytic
amount of PPTS (0.5 equiv) in dry dichloromethane
was refluxed for 3 h. The usual work-up led to a syrup
that was subjected to preparative TLC (ethyl acetate/
hexane 1:3) to obtain a 24% yield of inositol 6a and a
61% yield of inositol 6b.
tography (ethyl acetate/hexane 1:3), providing a 53%
20
yield of 1e as a yellow oil. ½aꢁD ¼ ꢀ29:7 (c 1.63, CHCl3).
1H NMR (CDCl3): d = 1.48 (s, 3H, CH3); 1.50 (s, 3H,
CH3); 3.11 (br s, 1H, OH); 3.64 (dd, 1H, J3,4 = 9.1 Hz,
J4,5 = 10.7 Hz, H-4); 4.00 (dd, 1H, J5,6 = 5.5
Hz, J4,5 = 10.7 Hz, H5); 4.45 (dt, 1H, J2,3 = 1.4 Hz,
J3,6 = 1.4 Hz, J3,4 = 9.1 Hz, H3); 4.79–4.95 (m, 3H,
H6 + CH2Ph); 7.06 (d, 1H, J3,2 = 1.4 Hz, H2); 7.28–
7.45 (m, 5H, 5 · Ar-H); 9.51 (s, 1H, CHO). 13C NMR
(CDCl3): d = 26.6; 26.7; 72.7; 73.4; 75.6; 79.6; 81.7;
112.5; 127.6; 127.8; 128.3; 138.1; 141.3; 145.7; 193.1.
MS (CI): m/z (%) = 305 (100, MH+); 247 (65,
MH+ꢀC3H6O). IR (KBr, cmꢀ1): 3456 (OH); 1688
(CO). Found: C, 67.15; H, 6.74; C17H21O5 requires C,
67.09; H, 6.62.
20
1
Compound 6a: ½aꢁD ¼ ꢀ43:9 (c 1.94, CHCl3). H NMR
(CDCl3): d = 1.45 (s, 3H, CH3); 1.46 (s, 3H, CH3); 1.81–
1.92 (m, 1H, HC-CH2S); 2.07–2.14 (m, 1H, HC-CH2S);
0
2.73 (dt, 1H, J1;1 ¼ 1:6 Hz, J1,6 = 10.6 Hz, J1,2
=
10.6 Hz, H1); 2.83–2.96 (m, 5H, 2 · CH2-S + OH);
3.51 (t, J4,5 = 9.8 Hz, J3,4 = 9.8 Hz, 1H, H4); 3.64 (dd,
1H, J5,6 = 7.8 Hz, J4,5 = 9.8 Hz, H5); 3.93 (dd, 1H,
J3,4 = 9.8 Hz, J2,3 = 10.6 Hz, H3); 3.94 (ddd, 1H,
J6,OH = 2.7 Hz, J5,6 = 7.8 Hz, J1,6 = 10.6 Hz, H6); 4.43
0
(d, 1H, J1;1 ¼ 1:6 Hz, S-CH-S); 4.70 (d, 1H, Jgem
11.3 Hz, CH2Ph); 4.90 (t, 1H, J1,2 = 10.6 Hz, J2,3
=
=
Acknowledgements
10.6 Hz, H2); 4.94 (d, 1H, Jgem = 11.3 Hz, CH2Ph);
Special thanks are due to Professor G. W. J. Fleet for
helpful discussions on this project. We also thank the
7.29–7.37 (m, 5H, 5 · Ar-H). 13C NMR (CDCl3):

J. M. Otero et al. / Tetrahedron: Asymmetry 16 (2005) 4045–4049
4049
´
´
(c) Soengas, R. G.; Estevez, J. C.; Estevez, R. J. Org. Lett.
Spanish Ministry of Education and Science for financial
´
´
2003, 5, 1423; (d) Soengas, R. G.; Estevez, J. C.; Estevez,
R. J. Tetrahedron: Asymmetry 2003, 14, 1653; (e) Soengas,
´
support for a grant to Jose M. Otero.
´
´
´
R. G.; Pampın, M. B.; Estevez, J. C.; Estevez, R. J.
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the Cambridge Crystallographic Data Centre as supple-
mentary publication no. CCDC 289417 4b. Copies of
the data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
[fax: (+44)1223-336-033; email: deposit@ccdc.cam.ac.uk].
Crystallographic data for 4b. C20H27NO6S2, M = 441.55,
T = 293(2) K. Orthorhombic, space group P212121 with
4. The structures (except stereochemistry) of the main
components of the rancinamycin complex were deter-
mined with IR, UV, and NMR spectra. Rancinamycin I is
a mixture of five isomeric components, designated Ia, Ib,
Ic, Id and Ie. Rancinamycin II is also a mixture of five
isomeric compounds, designated rancinamycins IIa–IIe.
Differences in the acyl group or in stereochemistry
probably account for the isomers. Rancinamycin III is a
mixture of four isomeric components. The differences
between the four isomers is unknown. Rancinamycin IV is
3,4-dihydroxybenzaldehyde. See: (a) Argoudelis, A. D.;
Pike, T. R.; Sprague, R. W. J. Antibiot. 1976, 29, 777; (b)
Argoudelis, A. D.; Sprague, R. W.; Mizsack, S. A. J.
Antibiot. 1976, 29, 787.
5. (a) Ferrier, R. J.; Middelton, S. Chem. Rev. 1993, 93, 2779;
(b) Rassu, G.; Auzzas, L.; Pinna, L.; Battistini, L.; Curti,
C. Stud. Nat. Prod. Chem. 2003, 29, 449–520; (c) Ogawa,
S. Trends Glycosci. Glycotechnol. 2004, 16, 33.
6. (a) Henry, C. R. Acad. Sci. Paris 1985, 120, 1265; (b)
Luzzio, F. A. Tetrahedron 2001, 57, 915; (c) Noboru, O.
In The Nitro Group in Organic Synthesis; Feuer, H., Ed.;
Organic Nitro Chemistry Series; Wiley-VCH: New York,
2001, Chapter 2.
˚
a = 5.193(5), b = 11.133(5), c = 37.150(5) A, a = 90ꢁ,
3
˚
b = 90ꢁ, c = 90ꢁ, V = 2148(2) A , Dc (Z = 4) = Ônot
measuredÕ.
F(000) = 936,
absorption
coeffi-
cient = 0.284 mmꢀ1. Data were obtained on a Smart-
CCD-1000 BRUKER diffractometer (graphite crystal
˚
monochromator, k = 0.71069 A) using the x = 2h scan
method; absorption corrections were applied. Refinement,
with anisotropic displacement parameters applied to each
of the non-hydrogen atoms, was by full-matrix least
squares on F2 (SHELXL-93) using all data;
2
2 1=2
wR2 ¼ ½RwðF o2 ꢀ F c2Þ =RwðF o2Þ ꢁ
.
12. Previous specific rotation attributed to compound 6b
24
{½aꢁD ¼ ꢀ9:3 (c 1.14, CHCl3)} is incorrect. See Ref. 9.
´
´
7. (a) Soengas, R. G.; Estevez, J. C.; Estevez, R. J.
13. Grundmann, C.; Ruske, W. Chem. Ber. 1953, 86, 939.
14. Perrin, D. D.; Armarego, W. L. F. Purification of
Laboratory Chemicals; Pergamon Press: New York, 1988.
Tetrahedron: Asymmetry 2003, 14, 3955; (b) Soengas, R.
´
´
G.; Estevez, J. C.; Estevez, R. J. Org. Lett. 2003, 5, 4457;