A new efficient synthesis of long-chain di- and triaminopolyols

Article abstract of DOI:10.1002/ejoc.200600276

The asymmetric synthesis of long-chain di- and triamino polyols is reported. The developed methodology is based on the functionalization of 3,3′-methylenebis{[6-(benzyloxy)-methoxy]cyclohept-3-en-1-ol} derivatives that allows the selective introduction of

Full text of DOI:10.1002/ejoc.200600276

FULL PAPER
DOI: 10.1002/ejoc.200600276
A New Efficient Synthesis of Long-Chain Di- and Triaminopolyols
Gérald Coste[a] and Sandrine Gerber-Lemaire*[a]
Keywords: Amino alcohols / Chain structures / Polyketides / Synthetic methods
The asymmetric synthesis of long-chain di- and triamino
polyols is reported. The developed methodology is based on
the functionalization of 3,3Ј-methylenebis{[6-(benzyloxy)-
methoxy]cyclohept-3-en-1-ol} derivatives that allows the
selective introduction of amine moieties at defined positions
of polyketide fragments. The versatile strategy disclosed
here requires few purification steps and may generate a
large panel of stereoisomers.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
studies, we demonstrated that meso-4 can be desymmetrized
and transformed into polyketides containing amino groups
at the terminal positions of the systems.[7c] Nevertheless, the
synthetic route requires a large number of steps and does
not allow the selective introduction of amino groups at in-
ternal positions of the polyketide chain. We report here a
further development of the non-iterative functionalization
of diolefin threo-5 for the efficient preparation of long-chain
di- and triamino polyols. In particular, pathways have been
developed for the selective protection of some alcohol moie-
ties of long-chain polyols[10] in order to introduce amino
groups at defined positions of the skeleton. Linear flexible
systems as well as diketal derivatives can be readily pro-
duced.
Introduction
Aminopolyols belonging to the large family of amino
sugars and deoxyamino sugars are molecules of high impor-
tance in medicinal chemistry and glycobiology,[1] therefore
many synthetic efforts have been directed toward the design
of efficient routes toward these derivatives.[2] Long-chain
polyketides containing amino groups are rare natural com-
pounds that display important biological properties. For ex-
ample, linearmycins,[3] which have been isolated from the
mycelial extracts of Streptomyces sp, display antifungal and
antibacterial activities, zwittermycin A,[4] an aminopolyol
antibiotic produced by Bacillus cereus UW 85, suppresses
certain plant diseases and is highly active against various
eukaryotes (Figure 1), and galantinic acid,[5] a nonpro-
teinogenic amino acid, has attracted much synthetic atten-
tion due to its unique structure and biological properties.
Nevertheless, few synthetic routes toward linear aminopoly-
ols have been reported thus far and are mostly limited to
short sequences.[6]
Figure 1. Natural long-chain aminopolyols.
Vogel’s group has developed a non-iterative asymmetric
synthesis of fifteen-carbon 1,3-polyols and heptahydroxy-
pentadecanals based on the stereoselective functionalization
of dialkenes of type meso-4[7] and ( )-threo-5,[8]which are
readily obtained from the bicyclo adducts resulting from
the double [4+3] cycloaddition of 2,2Ј-methylenedifuran to
1,1,3-trichloro-2-oxyallyl cation (Scheme 1).[9] In previous
Scheme 1.
Results and Discussion
Based on our previous results on the synthesis of hepta-
hydroxypentadecanals, diolefin (–)-5 was submitted to
ozonolysis followed by reductive treatment with Me2S and
then with an excess of Et2BOMe and NaBH4 at –30 °C[11]
to afford a mixture of bis(hemiacetals) 6 in 55% yield. Re-
[a] Laboratory of Glycochemistry and Asymmetric Synthesis,
Ecole Polytechnique Fédérale de Lausanne (EPFL)
Batochime, 1015 Lausanne, Switzerland
Fax: +41-21-693-93-55
E-mail: Sandrine.Gerber@epfl.ch
Eur. J. Org. Chem. 2006, 3903–3909
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3903

G. Coste, S. Gerber-Lemaire
FULL PAPER
action with camphorsulfonic acid in methanol, followed by ated derivative (+)-8 with vinyl acetate in the presence of
protection of the diol moiety as an acetonide, provided py- Candida cylindracea lipase (4800 Ummol–1) allowed the se-
ranosides 7 as a mixture of four isomers (87% yield, 2 steps) lective transacetylation of the primary alcohols with quanti-
due to the presence of two anomers at each hemiketal moi- tative yield. Interestingly, we found that this procedure
ety. Only two sets of signals (corresponding to anomers, could be applied to other semi-protected polyketides [( )-
2:1 ratio) can be distinguished in the NMR spectra of this 13[8b] and ( )-14[10]], thus providing a simple and efficient
derivative as a result of the quasi-symmetry of the molecule. method for the selective acetylation of primary alcohols in
Moreover, typical 13C NMR signals[12] were observed for the presence of free secondary hydroxy moieties. In all
the acetonide at C-4 and C-6 (δMe = 31.6 and 21.3 ppm), cases, the corresponding diacetates [( )-15 and ( )-16] were
thus establishing the syn relative configuration of the corre- obtained in quantitative yields.
sponding diol (Scheme 2).
Scheme 3.
Derivative (+)-12 was then converted into an intermedi-
ate triazide as above (Scheme 4). The acetyl groups of this
compound were methanolyzed directly under classical con-
ditions (K2CO3, MeOH), without intermediate purification,
and the azido groups were reduced by catalytic hydrogena-
tion. The remaining protective moieties were finally re-
moved by acidic hydrolysis (CF3COOH/H2O). This se-
quence afforded pentol (+)-17, with amino groups selec-
tively introduced at internal positions of the linear back-
bone, in 20% yield (five steps). In the course of our study,
Scheme 2.
amino groups were also easily introduced at the terminal
Treatment of bis(hemiacetals) 6 with tert-butyldimethyl- positions of linear polyols. For instance, diol (+)-18 [pre-
silyl trifluoromethanesulfonate (1.5 equiv.) under dilute pared from (+)-5[8b]] was submitted to a sequence of esteri-
conditions at –50 °C led to the highly regioselective silyl- fication with CH3SO2Cl followed by treatment with NaN3
ation of the alcohol at C-2, which is directed by intramo- to afford an intermediate diazido derivative, which was sub-
lecular hydrogen bonding between the hydroxy moiety at C- sequently reduced by catalytic hydrogenation and depro-
4 and the intracyclic oxygen atom at C-2ЈЈ.[13] Subsequent tected under acidic conditions to afford diaminohexol (–)-
reduction of the hemiacetal moieties afforded the monosily- 19 in 23% yield (4 steps). Interestingly, bis(hemiacetals) 6
lated polyol (+)-8 in 50% yield (2 steps). The 1,3-syn-diol could also be directly derivatized into semi-protected diami-
(+)-8 was converted into the corresponding acetonide [ace- nopolyols. Treatment with camphorsulfonic acid in meth-
tone/Me2C(OMe)2, p-TsOH cat.] to provide the semi-pro- anol afforded a mixture of bis(methyl pyranosides) 20 (same
tected polyol (+)-9, which was used for the introduction of isomeric ratio as 6 and 7). At this stage, esterification of the
three amino groups on the polyketide skeleton. The remain- secondary alcohols in the presence of CH3SO2Cl followed
ing alcohols were esterified with CH3SO2Cl, and displace- by displacement of the resulting dimesylate with NaN3 and
ment of the resulting trimesylate with NaN3 provided triaz- selective reduction of the azido groups [H2, Pd(OH)2/C,
ide 10. This intermediate was directly submitted to catalytic MeOH] provided derivative 21, which is functionalized with
hydrogenation [H2, Pd(OH)2/C, MeOH] followed by acidic two amino groups at positions C-2 and C-4. All our
removal of the protecting groups to deliver triaminopentol attempts to remove the benzyloxymethyl ethers from 21
(+)-11 in 27% yield (four steps).
were unsuccessful. Acetyl groups were thus envisaged for
We next targeted the introduction of amino groups at the protection of the alcohols at C-4Ј and C-4ЈЈ. Catalytic
three internal positions of the polyolic system. For this pur- hydrogenation of 7 in the presence of Raney nickel led to
pose, we studied the selective protection of the primary 22 by reduction of the benzyloxymethyl ethers. Acetylation
alcohols of polyketide chains without affecting internal sec- of the resulting diol (Ac2O/pyridine, DMAP cat.), followed
ondary alcohols (Scheme 3). Treatment of the monosilyl- by acidic removal of the acetonide moiety, allowed intro-
3904
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3903–3909

Long-Chain Di- and Triaminopolyols
FULL PAPER
duction of azido groups at C-2 and C-4, as above. Meth-
anolysis of the acetates delivered 23 in 37% yield (5 steps).
Finally, catalytic hydrogenation in the presence of Pd-
(OH)2/C provided diamino bis(methyl pyranosides) 24 in
84% yield.
Experimental Section
General: Commercial reagents (Fluka, Aldrich) were used without
purification. Solvents were filtered prior to use (Innovative Tech-
nology). Light petroleum ether refers to the fraction boiling at 40–
60 °C. Solutions after reaction and extraction were concentrated at
reduced pressure in
a rotary evaporator. Liquid/solid flash
chromatography (FC): columns of silica gel (0.040–0.63 mm,
Merck no. 9385 silica gel 60, 240–400 mesh). TLC for reaction
monitoring: Merck silica gel 60F254 plates; detection by UV light;
Pancaldi reagent [(NH4)6MoO4, Ce(SO4)2, H2SO4, H2O] or
KMnO4. IR spectra: Perkin–Elmer 1420 spectrometer. 1H NMR
spectra: Bruker ARX-400 spectrometer (400 MHz); δH in ppm rela-
tive to the solvent’s residual 1H signal [CHCl3: δH = 7.27 ppm;
CH3OD: δH = 3.34 ppm; C6H6: δH = 7.3 ppm] as internal reference;
all 1H assignments were confirmed by 2D COSY-45 spectra. 13C
NMR spectra: same instrument as above (100.6 MHz); δC in ppm
relative to solvent’s C signal [CDCl3: δC = 77.0 ppm; CD3OD: δC
= 48.5 ppm; C6D6: δC = 128.5 ppm] as internal reference; coupling
constants are given in Hz. MS: Nermag R-10-10C, chemical ioniza-
tion (NH3) mode. MALDI-TOF, ESI and HR-MALDI-MS mass
spectra were measured at the Swiss Institute of Technology Mass
Spectral Facility. Elemental analyses: Ilse Beetz, 96301 Kronach,
Germany.
Synthesis of 7: A stream of ozone was passed through a solution
of diolefin (–)-5 (500 mg, 0.861 mmol) in 26 mL of dichlorometh-
ane at –78 °C for 5 min. A stream of dry O2 was then passed
through the solution for 2 min, and Me2S (250 µL, 3.45 mmol,
4 equiv.) was added dropwise. After stirring at –78 °C for 10 min,
the solvent was evaporated at 0 °C. The residue was taken up in
THF/MeOH (3:1; 16 mL) at 0 °C and Et2BOMe (1  in THF;
5.2 mL, 5.17 mmol, 6 equiv.) was added. The resulting mixture was
stirred at 0 °C for an additional 1 h. The solution was cooled to
–30 °C and NaBH4 (260 mg, 6.891 mmol, 8 equiv.) was added por-
tionwise. The temperature was kept below –20 °C for 2 h. The reac-
tion mixture was poured into water (25 mL) and extracted with
EtOAc (20 mL, 3 times). The combined organic extracts were dried
with MgSO4 and concentrated in vacuo. Purification of the residue
by flash chromatography (5% to 10% of MeOH in CH2Cl2) af-
forded the intermediate bis(hemiketal) 6 as a colourless oil (274 mg,
55%). Camphorsulfonic acid (5 mg, 0.023 mmol, 0.2 equiv.) was
added to a solution of 6 (65 mg, 0.113 mmol) in MeOH (3 mL) and
the mixture was stirred at 25 °C for 2 h. The solution was then
poured into a satd. aq. solution of NaHCO3 (10 mL) and extracted
with EtOAc (10 mL, 3 times). The combined organic extracts were
washed with brine (20 mL), dried with MgSO4 and concentrated
in vacuo. The resulting diol was dissolved in a mixture of acetone
and dimethoxypropane (0.3/3 mL), and treated with p-toluenesul-
fonic acid (8 mg, 0.042 mmol, 0.4 equiv.) at 0 °C. The resulting mix-
ture was stirred at 0 °C for 1 h. The solution was poured into a
satd. aq. solution of NaHCO3 (10 mL) and extracted with EtOAc
Scheme 4.
Conclusions
An asymmetric synthesis of long-chain polyketides con-
taining amino groups has been developed by the function- (10 mL, 3 times). The combined organic extracts were dried with
MgSO4 and concentrated in vacuo. Purification of the residue by
flash chromatography (3% MeOH in CH2Cl2) afforded 7 as a
colourless oil (63 mg, 87%, 2:1 ratio for two distinct sets of signals).
alization of 3,3Ј-methylenebis{[6-(benzyloxy)methoxy]cy-
clohept-3-en-1-ol} [(–)-5]. While very few methods have
been reported for the preparation of linear aminopolyols,
the methodology disclosed here gives access to the selective
introduction of amino groups at various positions of poly-
ketide fragments. Furthermore, the synthetic pathways re-
quire few purification steps, as exemplified by the conver-
sion of (–)-5 into triaminopentol (+)-11, which was per-
formed with the isolation of only three intermediates over
nine steps.
IR (film): ν = 2940, 1450, 1380, 1260, 1200, 1160, 1115, 1045, 980,
˜
1
740, 700 cm–1. H NMR (400 MHz, MeOD): δ = 7.35–7.25 (m, 10
2
Harom.), 4.82 (s, 1.34 H, 6ЈЈmaj-H, 6IVmaj-H), 4.81, 4.78 [2 d, JH,H
= 5.6, 6.9 Hz, 4 H, 2×CH2(BOM)], 4.60 (s, 4 H, 2×CH2Ph), 4.27
(m, 0.66 H, 6ЈЈmin-H, 6IVmin-H), 4.13–3.97 (m, 2 H, 2ЈЈ-H, 2IV-H),
4.23–3.84 (2 m, 4 H, 4-H, 4ЈЈ-H, 4IV-H, 6-H), 3.40, 3.30 (2 s, 6 H,
2×-OMe), 2.30–1.90, 1.60–1.40 (2 m, 10 H, 5-H2, 3ЈЈ-H2, 3IV-H2,
5ЈЈ-H2, 5IV-H2), 1.70–1.50, 1.30–1.10 (2 m, 4 H, 1Ј-H2, 1ЈЈЈ-H2),
Eur. J. Org. Chem. 2006, 3903–3909
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3905

G. Coste, S. Gerber-Lemaire
FULL PAPER
1.26, 1.16 (2 s, 6 H, 2×2-Me) ppm. 13C NMR (100 MHz, MeOD):
(film): ν = 3440, 2945, 1460, 1430, 1380, 1255, 1200, 1160, 1040,
˜
1
δ = 140.4 (s, 2 Carom.), 130.4, 130.0, 129.7 (3 d, JC,H = 160, 159,
835, 780, 740, 700 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.43–
1
2
160 Hz, 10 Carom.), 103.6, 103.5 (2 d, JC,H = 160 Hz, C-6ЈЈmin., C-
7.27 (m, 10 Harom.), 4.86 [2 d, JH,H = 7.6, 8.4 Hz, 4 H,
6IVmin.), 101.5, 101.2 (2 d, 1JC,H = 160, 162 Hz, C-6ЈЈmaj., C-6IVmaj.),
2×CH2(BOM)], 4.67 (2 d, 2JH,H = 10.2, 11.4 Hz, 4 H, 2×CH2Ph),
4.17–4.04 (2 m, 4 H, 3-H, 5-H, 7-H, 2ЈЈ-H), 4.02–3.87 (2 m, 2 H,
1
100.8 (s, C-2), 95.0, 94.8 [2 t, JC,H = 163 Hz, 2×CH2(BOM)maj.],
95.1, 94.9 [2 t, 1JC,H = 163 Hz, 2×CH2(BOM)min.], 74.5, 74.4 (2 d, 4Ј-H, 6Ј-H), 3.86–3.77, 3.76–3.69 (2 m, 4 H, 1-H2, 4ЈЈ-H2), 1.89–
1
1JC,H = 148, 146 Hz, C-2ЈЈmin., C-2IVmin.), 72.0, 71.8 (2 d, JC,H
=
1.72 (2 m, 6 H, 2-H2, 1ЈЈ-H2, 3ЈЈ-H2), 1.68–1.52 (m, 8 H, 4-H2, 6-
148, 144 Hz, C-2ЈЈmaj., C-2IVmaj.), 71.5, 71.4 (2 t, JC,H = 144 Hz, H2, 8-H2, 5Ј-H2), 1.35, 1.33 (2 s, 6 H, 2×CH3-2Ј), 0.89 [s, 9 H,
1
2×CH2Ph), 70.6, 70.0, 68.3, 67.5 (4 d, C-4min., C-6min., C-4ЈЈmin.
,
C(CH3)3], 0.08 [2 s, 6 H, Si(CH3)2] ppm. 13C NMR (100 MHz,
C-4IVmin.), 68.2, 67.4, 66.4, 65.7 (4 d, 1JC,H = 140, 139, 145, 144 Hz, CDCl): δ = 137.9, 137,8 (2 s, 2 Carom.), 128.9, 128.2 (2 d, JC,H
=
1
1
1
C-4maj., C-6maj., C-4ЈЈmaj., C-4IVmaj.), 57.8, 57.7 (2 q, JC,H
=
160 Hz, 10 Carom.), 98.9 (s, C-2Ј), 95.3, 95.1 [2 t, JC,H = 163 Hz,
1
1
148 Hz, 2×OMemin.), 56.2, 55.9 (2 q, JC,H = 147, 142 Hz,
2×CH2(BOM)], 74.2, 74.0 (2 d, JC,H = 149 Hz, C-3, C-2ЈЈ), 70.4
2×OMemaj), 45.3, 44.4 (2 t, JC,H = 127, 128 Hz, C-1Јmaj., C- (t, 1JC,H = 141 Hz, 2×CH2Ph), 68.3 (d, 1JC,H = 140 Hz, C-7), 66.1,
1
1ЈЈЈmaj.), 44.6, 44.0 (2 t, JC,H = 127, 128 Hz, C-1Јmin., C-1ЈЈЈmin.), 65.9 (2 d, 1JC,H = 137, 141 Hz, C-4Ј, C-6Ј), 65.2 (d, 1JC,H = 143 Hz,
1
41.2, 40.6, 39.1 (3 t, JC,H = 128, 130, 126 Hz, C-5, C-3ЈЈ, C-3IV,
C-5), 59.9, 59.8 (2 t, JC,H = 146 Hz, C-1, C-4ЈЈ), 43.8, 43.2, 42.9,
1
1
1
C-5ЈЈ, C-5IV), 31.6, 21.3 (2 q, JC,H = 123, 127 Hz, 2×Me-2) ppm.
42.6 (4 t, 1JC,H = 127, 124, 126 Hz, C-4, C-6, C-8, C-5Ј), 38.3, 38.1,
1
1
MALDI-MS: m/z = 667.35 [M+Na], 683.38 [M+K]. C36H52O10 38.0 (3 t, JC,H = 126 Hz, C-2, C-1ЈЈ, C-3ЈЈ), 30.5, 20.1 (2 q, JC,H
(644.792): calcd. C 67.06, H 8.13; found C 67.06, H 8.16.
= 123, 128 Hz, 2×CH3-2Ј), 26.2 [q, 1JC,H = 126 Hz, C(CH3)3], 18.3
(s, CMe3), –4.2, –4.3 [2 q, 1JC,H = 118 Hz, Si(CH3)2] ppm. MALDI-
MS: m/z = 757.40 [M+Na], 773.39 [M+K]. C40H66O10Si (735.03):
calcd. C 65.36, H 9.03, Si 3.82; found C 65.33, H 9.02, Si 3.79.
Synthesis of (+)-8: 2,6-Lutidine (100 µL, 0.855 mmol, 3 equiv.) and
a
solution of tert-butyldimethylsilyl trifluoromethanesulfonate
(0.5  in CH2Cl2; 900 µL, 0.456 mmol, 1.6 equiv.) were added to a
solution of 6 (165 mg, 0.285 mmol) in CH2Cl2 (2.8 mL) at –50 °C.
The resulting mixture was stirred for 1.5 h and then poured into a
satd. aq. solution of NaHCO3 (15 mL) and extracted with EtOAc
(10 mL, 3 times). The combined organic extracts were washed with
brine (30 mL), dried with MgSO4 and concentrated in vacuo. The
crude residual oil was dissolved in MeOH (3 mL) and treated with
NaBH4 (90 mg, 2.28 mmol, 8 equiv.) at 25 °C for 1 h. The reaction
mixture was poured into water (20 mL) and extracted with EtOAc
(20 mL, 3 times). The combined organic extracts were washed with
brine (50 mL), dried with MgSO4 and concentrated in vacuo. Puri-
fication of the residue by flash chromatography (4% MeOH in
CH2Cl2) afforded (+)-8 as a pale-yellow oil (99 mg, 50% over 2
General Procedure for the Lipase-Catalyzed Transacetylation of Po-
lyol Derivatives: A 0.1  solution of polyol in vinyl acetate was vig-
orously stirred in the presence of lipase from Candida Cylindracea
(5000 Ummol–1, 3.85 Umg–1) at 25 °C for 6 h. The suspension was
then filtered through a pad of Celite. The filtrate was concentrated
in vacuo and the resulting oil was purified by flash chromatography
(CH2Cl2/MeOH, 97:3 to 95:5) in almost quantitative yields.
Synthesis of (+)-12: The general procedure applied to (+)-8 (60 mg,
0.086 mmol) provided (+)-12 as a pale-yellow oil (67 mg, quant.).
23
23
[α]42035 = +56; [α] = +47; [α] = +24 (c = 2.5, MeOH). IR (film):
435
589
ν = 3460, 2945, 2860, 1740, 1460, 1430, 1370, 1250, 1100, 1040,
˜
1
835, 780, 740, 700 cm–1. H NMR (400 MHz, MeOD): δ = 7.35–
23
23
23
steps). [α]
= +31; [α] = +26; [α]
= +13 (c = 1.4, MeOH).
405
435
577
2
IR (film): ν = 3445, 2930, 1645, 1450, 1255, 1100 cm–1. H NMR
1
7.24 (m, 10 Harom.), 4.83, 4.79 [2 d, JH,H = 6.7, 6.4 Hz, 4 H,
2×CH2(BOM)], 4.62 (d, JH,H = 8.8 Hz, 4 H, 2×CH2Ph), 4.18 (t,
˜
2
(400 MHz, MeOD): δ = 7.35–7.22 (m, 10 Harom.), 4.86 [br. s, 4 H,
2×CH2(BOM)], 4.67 (br. s, 4 H, 2×CH2Ph), 4.20–4.12 (m, 1 H,
9-H), 4.09–3.92 (m, 4 H, 3-H, 5-H, 7-H, 13-H), 3.89–3.81 (m, 1 H,
11-H), 3.70–3.62 (m, 4 H, 1-H2, 15-H2), 1.91–1.77 (m, 4 H, 2-H2,
14-H2), 1.77–1.44 (m, 10 H, 4-H2, 6-H2, 8-H2, 10-H2, 12-H2), 0.92
[s, 9 H, C(CH3)3], 0.13 [2 s, 6 H, Si(CH3)2] ppm. 13C NMR
(100 MHz, MeOD): δ = 138.3 (s, 2 Carom.), 128.4, 128.0, 127.7 (3
3JH,H = 6.24 Hz, 4 H, 1-H2, 15-H2), 4.18–4.15 (m, 1 H, 11-H),
4.11–3.95 (m, 4 H, 3-H, 5-H, 7-H, 13-H), 3.91–3.78 (m, 1 H, 9-H),
2.0 [s, 6 H, 2×CH3(OAc)], 1.93–1.85 (m, 4 H, 2-H2, 14-H2), 1.75–
1.47 (m, 10 H, 4-H2, 6-H2, 8-H2, 10-H2, 12-H2), 0.90 [s, 9 H,
C(CH3)3], 0.11 [2 s, 6 H, Si(CH3)2] ppm. 13C NMR (100 MHz,
MeOD): δ = 171.9 [s, 2×C=O(OAc)], 138.2 (s, 2 Carom.), 128.4,
1
1
1
127.9, 127.7 (3 d, JC,H = 159, 160, 159 Hz, 10 Carom.), 94.5, 94.4,
d, JC,H = 159, 160, 159 Hz, 10 Carom.), 94.5 [2 t, JC,H = 163 Hz,
1
1
1
[2 t, JC,H = 163 Hz, 2×CH2(BOM)], 72.8 (d, JC,H = 142 Hz, C-
2×CH2(BOM)], 73.5, 73.3 (d, JC,H = 142 Hz, C-3, C-13), 69.8,
1
1
69.3 (2 t, 1JC,H = 140, 142 Hz, 2×CH2Ph), 67.8 (d, 1JC,H = 146 Hz,
3, C-13), 69.9, 69.7 (t, JC,H = 140 Hz, 2×CH2Ph), 67.6 (d, JC,H
1
1
1
= 146 Hz, C-11), 67.3 (d, JC,H = 140 Hz, C-9), 66.9, 64.8 (2 d,
C-11), 67.5 (d, JC,H = 140 Hz, C-9), 67.1, 64.9 (2 d, JC,H = 143,
144 Hz, C-5, C-7), 58.5, 58.3 (2 t, 1JC,H = 148, 147 Hz, C-1, C-15),
45.9, 45.4, 44.6, 44.0, 43.4 (5 t, 1JC,H = 127, 125, 125, 124, 128 Hz,
C-4, C-6, C-8, C-10, C-12), 38.4, 38.3 (2 t, 1JC,H = 126 Hz, C-2, C-
14), 25.4 [q, JC,H = 129 Hz, C(CH3)3], 17.8 (s, CMe3), –4.5, –5.0
[2 q, JC,H = 118 Hz, Si(CH3)2] ppm. MALDI-MS: m/z = 716.75
1JC,H = 143, 144 Hz, C-5, C-7), 61.4 (t, JC,H = 148 Hz, C-1, C-
1
1
15), 46.0, 45.4, 44.4, 43.8, 43.2 (5 t, JC,H = 127, 125, 125, 124,
128 Hz, C-4, C-6, C-8, C-10, C-12), 34.4, 34.3 (t, JC,H = 126 Hz,
C-2, C-14), 25.4 [q, JC,H = 129 Hz, C(CH3)3], 19.9 (s, CMe3),
–4.9, –5.3 [2 q, JC,H = 118 Hz, Si(CH3)2] ppm. CI-MS (NH3): m/z
1
1
1
1
1
= 780 [M+H]. C41H66O12Si (779.041): calcd. C 63.21, H 8.54, Si
3.61; found C 63.27, H 8.60, Si 3.51.
[M+Na], 732.71 [M+K]. C37H62O10Si (694.97): calcd. C 63.94, H
8.99, Si 4.04; found C 64.05, H 8.83, Si 3.90.
Synthesis of (+)-9: p-Toluenesulfonic acid (5 mg, 0.026 mmol,
Synthesis of ( )-15: The general procedure applied to ( )-13
0.3 equiv.) was added to a solution of (+)-8 (60 mg, 0.086 mmol) (30 mg, 0.052 mmol) provided ( )-15 as a colourless oil (35 mg,
in a mixture of acetone and dimethoxypropane (0.3/3 mL) and the
mixture was stirred at 0 °C for 1 h. The solution was poured into
a satd. aq. solution of NaHCO3 (10 mL) and extracted with EtOAc
(10 mL, 3 times). The combined organic extracts were washed with
brine (30 mL), dried with MgSO4 and concentrated in vacuo. Puri-
quant.). IR (film): ν = 3440, 2940, 1735, 1455, 1370, 1245, 1100,
˜
1
1090, 740, 700 cm–1. H NMR (400 MHz, MeOD): δ = 7.37–7.25
2
(m, 10 Harom.), 4.84, 4.81 [2 d, JH,H = 7.0, 6.9 Hz, 4 H,
3
2×CH2(BOM)], 4.63 (s, 4 H, 2×CH2Ph), 4.18 (t, JH,H = 6.8 Hz,
4 H, 1-H2, 15-H2), 4.04–3.98 (m, 6 H, 3-H, 5-H, 7-H, 9-H, 11-H,
3
fication of the residue by flash chromatography (3% MeOH in
13-H), 2.01 [s, 6 H, 2×CH3(OAc)], 1.90 (t, JH,H = 5.5 Hz, 4 H, 2-
23
CH2Cl2) afforded (+)-9 as a pale-yellow oil (54 mg, 85%). [α]
=
H2, 14-H2), 1.64–1.50 (m, 10 H, 4-H2, 6-H2, 8-H2, 10-H2, 12-H2)
405
23
23
23
+61; [α] = +52; [α] = +27; [α] = +26 (c = 0.95, CHCl3). IR
ppm. 13C NMR (100 MHz, MeOD): δ = 172.9 [s, 2×C=O(OAc)],
435
577
589
3906
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3903–3909

Long-Chain Di- and Triaminopolyols
FULL PAPER
139.3 (s, Carom.), 129.4, 128.9, 128.7 (3 d, 1JC,H = 160, 159, 160 Hz,
Synthesis of (+)-17: The general procedure was applied to com-
1
Carom.), 95.5 [t, JC,H = 164 Hz, 2×CH2(BOM)], 74.1, 73.9, 70.1, pound (+)-12 (150 mg, 0.193 mmol). In this case, the intermediate
1
68.1, 67.8, 65.8 (6 d, JC,H = 143, 144, 140, 142, 140, 146 Hz, C-3,
triazide was treated with K2CO3 (2 equiv.) in methanol prior to
1
C-5, C-7, C-9, C-11, C-13), 70.9 (t, JC,H = 144 Hz, 2×CH2Ph),
catalytic hydrogenation. Compound (+)-17 was obtained as a white
1
23
23
62.4 (t, JC,H = 151 Hz, C-1, C-15), 46.6, 46.4, 45.9, 44.5, 44.2 (5
foam (13 mg, 20% yield over 5 steps). [α] = +3.5; [α] = +1 (c
435 589
1
t, JC,H = 120, 123, 127, 125, 126 Hz, C-4, C-6, C-8, C-10, C-12), = 0.11, MeOH). IR (KBr): ν = 3405, 1740, 1650, 1560, 1515,
˜
1
1
1
35.5 (t, JC,H = 127 Hz, C-2, C-14), 20.9 [q, JC,H = 129 Hz,
2×Me(OAc)] ppm. ESI-MS: m/z = 665.29 [M+H]. MALDI
HRMS: calcd. for [C35H52O12 +Na] 687.3356; found 687.3359.
1070 cm–1. H NMR (400 MHz, D2O): δ = 3.99–3.82 (m, 3 H, 3-
H, 7-H, 13-H), 3.73–3.52 (m, 7 H, 5-H, 9-H, 11-H, 1-H2, 15-H2),
1.97–1.43 (m, 14 H, 2-H2, 4-H2, 6-H2, 8-H2, 10-H2, 12-H2, 14-H2)
ppm. 13C NMR (100 MHz, D2O): δ = 69.5, 69.2, 69.0 (C-3, C-7,
C-13), 61.2, 60.9, 60.6, 60.3 (C-1, C-5, C-9, C-11, C-15), 41.6, 41.5,
40.3, 39.5, 39.4, 39.3, 38.9 (C-2, C-4, C-6, C-8, C-10, C-12, C-14)
ppm. CI-MS (NH3): m/z = 338 [M+H]. MALDI HRMS: calcd.
for [C15H35N3O5 +Na] 360.2474; found 360.2477.
Synthesis of ( )-16: The general procedure applied to ( )-14
(45 mg, 0.078 mmol) provided ( )-16 as a colourless oil (55 mg,
quant.). IR (film): ν = 3500, 2940, 1735, 1450, 1375, 1245,
˜
1040 cm–1. 1H NMR (400 MHz, MeOD): δ = 7.37–7.15 (m, 10
2
Harom.), 4.83, 4.80 [2 d, JH,H = 7.2, 7.4 Hz, 4 H, 2×CH2(BOM)],
3
Synthesis of (–)-19: The general procedure applied to (+)-18
(380 mg, 0.592 mmol) afforded (–)-19 (46 mg, 23% yield over four
4.63 (s, 4 H, 2×CH2Ph), 4.19 (t, JH,H = 6.6 Hz, 4 H, 1-H2, 8ЈЈ-
H2), 4.17–4.07 (m, 2 H, 2ЈЈ-H, 4ЈЈ-H), 4.05–3.95 (m, 4 H, 3-H, 4Ј-
H, 6Ј-H, 6ЈЈ-H), 2.00 [s, 6 H, 2×CH3(OAc)], 1.90–1.87 (m, 4 H, 2-
H2, 7ЈЈ-H2), 1.70–1.47, 1.55–1.47 (2 m, 10 H, 4-H2, 5Ј-H2, 1ЈЈ-H2,
3ЈЈ-H2, 5ЈЈ-H2), 1.43, 1.29 (2 s, 6 H, 2×Me-2Ј) ppm. 13C NMR
(100 MHz, MeOD): δ = 171.9 [s, 2×C=O(OAc)], 138.0 (s, 2 Carom.),
128.4, 127.9, 127.7 (3 d, 10 Carom.), 98.9 (s, C-2Ј), 94.6, 94.5, [2 t,
2×CH2(BOM)], 73.5, 73.4, (2 d, C-3, C-6ЈЈ), 69.8 (t, 2×CH2Ph),
67.5, 66.4, 65.3, 64.4 (4 d, C-4Ј, C-6Ј, C-2ЈЈ, C-4ЈЈ), 61.4 (t, C-1, C-
8ЈЈ), 44.8, 44.5, 43.6, 43.0, 37.6 (5 t, C-4, C-5Ј, C-1ЈЈ, C-3ЈЈ, C-5ЈЈ),
34.5, 34.4 (2 t, C-2, C-7ЈЈ), 29.6, 19.9 (2 q, 2×Me-2Ј), 19.2 [q,
2×Me(OAc)] ppm. ESI-MS: m/z = 705.33 [M+H]. MALDI
HRMS: calcd. for [C38H56O12 +Na] 727.3669; found 727.3665.
23
steps). [α]
= –4 (c = 0.16, MeOH). IR (KBr): ν = 3040, 1655,
˜
589
1565, 1435, 1075, 795 cm–1. H NMR (400 MHz, D2O): δ = 4.02–
3.94 (m, 6 H, 3-H, 5-H, 7-H, 9-H, 11-H, 13-H), 3.11–3.01 (m, 4 H,
1-H2, 15-H2), 1.82–1.60 (m, 14 H, 2-H2, 4-H2, 6-H2, 8-H2, 10-H2,
12-H2, 14-H2) ppm. 13C NMR (100 MHz, D2O): δ = 68.05, 66.6,
66.5, 66.3, 64.8 (C-3, C-5, C-7, C-9, C-11, C-13), 45.1, 44.9, 44.6,
44.4, 43.8 (C-4, C-6, C-8, C-10, C-12), 38.2, 37.5 (C-1, C-15), 38.0,
37.9 (C-2, C-14) ppm. MALDI-MS: m/z = 339.10 [M+H], 361.050
[M+Na]. MALDI HRMS: calcd. for [C15H34N2O6 +Na] 361.2315;
found 361.2328.
1
Synthesis of 21: Camphorsulfonic acid (15 mg, 0.060 mmol,
0.2 equiv.) was added to a solution of 6 (175 mg, 0.302 mmol) in
MeOH (3 mL) and the mixture was stirred at 25 °C for 2 h. The
solution was poured into a satd. aq. solution of NaHCO3 (20 mL)
and extracted with EtOAc (20 mL, 3 times). The combined organic
extracts were washed with brine (30 mL), dried with MgSO4 and
concentrated in vacuo. The crude residual oil was dissolved in
CH2Cl2 (3 mL) and treated at 0 °C with triethylamine (380 µL,
2.72 mmol, 9 equiv.) and methanesulfonyl chloride (110 µL,
0.907 mmol, 3 equiv.). After stirring at 0 °C for 1 h, the mixture
was poured into a satd. aq. solution of NH4Cl (20 mL) and ex-
tracted with EtOAc (20 mL, 3 times). The combined organic ex-
tracts were washed with brine (30 mL), dried with MgSO4 and con-
centrated in vacuo. The resulting dimesylate was dissolved in DMF
(6 mL) and treated with sodium azide (200 mg, 3.02 mmol,
10 equiv.) at 60 °C for 12 h. The mixture was poured into water
(20 mL) and extracted with EtOAc (20 mL, 3 times). The combined
organic extracts were washed with brine (30 mL), dried with
MgSO4 and concentrated in vacuo. The residue was dissolved in
MeOH (2 mL). A catalytic amount of 10% Pd(OH)2/C was added
and the resulting mixture was vigorously stirred under hydrogen
(1 atm.). After 4 h, the mixture was filtered through a pad of Celite
and concentrated in vacuo. Purification of the residue by flash
chromatography (5–10% of NH4OH in CH3CN) afforded 21 as a
colourless oil (66 mg, 36% over 4 steps, 2:1 ratio for two distinct
General Procedure for the Conversion of Semi-Protected Polyols (+)-
9, (+)-12 and (+)-18 into Di- and Triaminopolyols: Triethylamine
(4.5 equiv. per free alcohol group) and methanesulfonyl chloride
(1.5 equiv. per free alcohol group) were added to a solution of the
semi-protected polyol in CH2Cl2 (0.1 ) at 0 °C. The solution was
stirred at 0 °C for 2 h and then poured into a satd. aq. solution of
NH4Cl and extracted with EtOAc (3 times). The combined organic
extracts were washed with brine, dried with MgSO4 and concen-
trated in vacuo. The residual oil was dissolved in DMF (0.75 )
and treated with sodium azide (5 equiv. per mesylate group) at
60 °C for 12 h. The mixture was poured into water and extracted
with EtOAc (3 times). The combined organic extracts were washed
with brine, dried with MgSO4 and concentrated in vacuo. The re-
sidual oil was dissolved in MeOH (0.1 ). A catalytic amount of
Pd(OH)2 was added and the resulting mixture was vigorously
stirred under hydrogen (1 atm.). At the end of the reaction (moni-
tored by TLC: CH3CN/NH4OH), the mixture was filtered through
a pad of Celite and concentrated in vacuo. The crude intermediate
was dissolved in CF3COOH/H2O (4:1) and vigorously stirred at
25 °C. After completion of the reaction (monitored by TLC:
CH3CN/NH4OH), the solvents were removed under vacuo. The
crude oil was purified by flash chromatography (CH3CN/NH4OH,
2:1 to 1:2) to afford the aminopolyols as white foams.
Synthesis of (+)-11: The general procedure applied to compound
(+)-9 (200 mg, 0.272 mmol) afforded (+)-11 (40 mg, 27% yield over
sets of signals). IR (film): ν = 3370, 3295, 2935, 1670, 1450, 1385,
˜
1
1165, 1115, 1040, 970, 740, 700 cm–1. H NMR (400 MHz, C6D6):
23
23
four steps). [α] = +5.5; [α] = +3 (c = 0.19, MeOH). IR (KBr):
δ = 7.33–7.22 (m, 10 Harom.), 4.84–4.80 (m, 2 H, 6Ј-H, 6ЈЈ-H), 4.86,
435
589
ν = 3405, 1740, 1650, 1560, 1515, 1070 cm–1. H NMR (400 MHz,
4.82 [2 d, JH,H = 6.8, 6.5 Hz, 4 H, 2×CH2(BOM)], 4.68, 4.67 (s,
1
3
˜
D2O): δ = 4.1–3.88 (m, 5 H, 3-H, 5-H, 7-H, 9-H, 13-H), 3.46–3.34 4 H, 2×CH2Ph), 4.43–4.34 (m, 2 H, 2Ј-H, 2ЈЈ-H), 4.11–4.06, 3.96–
(m, 1 H, 11-H), 3.19–3.00 (m, 4 H, 1-H2, 15-H2), 1.95–1.54 (m, 14 3.88 (2 m, 2 H, 4Ј-H, 4ЈЈ-H), 3.35, 3.30 (2 s, 6 H, 2×OMe), 3.40–
H, 2-H2, 4-H2, 6-H2, 8-H2, 10-H2, 12-H2) ppm. 13C NMR 3.24 (m, 2 H, 2-H, 4-H), 2.43–2.26, 2.12–2.03 (2 m, 4 H, 5Ј-H2, 5ЈЈ-
(100 MHz, D2O): δ = 70.2, 69.8, 68.4, 68.3 (4 d, C-3, C-5, C-7, C-
9, C-13), 46.4, 46.3, 46.0, 43.8 (4 t, C-4, C-6, C-8, C-10, C-12),
40.1, 39.9, 39.7, 39.6, 39.4 (C-1, C-2, C-11, C-14, C-15) ppm.
MALDI-MS: m/z = 338.483 [M+H], 360.445 [M+Na]. MALDI
HRMS: calcd. for [C15H35N3O5 +H] 338.2653; found 338.2664.
H2), 1.87–1.64, 1.61–1.33 (2 m, 10 H, 1-H2, 3-H2, 5-H2, 3Ј-H2, 3ЈЈ-
H2) ppm. 13C NMR (100 MHz, C6D6): δ = 138.7, 138.6 (2 s, 2
1
Carom.), 128.6, 128.2, 128.0 (3 d, JC,H = 160, 158, 163 Hz, 10
Carom.), 99.3 (2 d, 1JC,H = 156 Hz, C-6Ј, C-6ЈЈ), 92.9, 92.8 [2 t, 1JC,H
= 163 Hz, 2×CH2(BOM)], 69.9, 69.6 (2 d, 1JC,H = 140 Hz, 142, C-
Eur. J. Org. Chem. 2006, 3903–3909
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3907

G. Coste, S. Gerber-Lemaire
FULL PAPER
1
2Ј, C-2ЈЈ), 69.4, 69.3 (2 t, JC,H = 143 Hz, 2×CH2Ph), 66.7, 64.5
0.145 mmol) was dissolved in MeOH (1.5 mL). A catalytic amount
of Pd(OH)2 was added and the resulting mixture was vigorously
stirred under hydrogen (1 atm.). After 4 h, the mixture was filtered
through a pad of Celite and concentrated in vacuo. Purification of
the residue by flash chromatography (20% of NH4OH in CH3CN)
afforded 24 as a colourless oil (44 mg, 84%, 2:1 ratio for two dis-
1
1
(2 d, JC,H = 142 Hz, C-4Ј, C-4ЈЈ), 54.6, 54.5 (2 q, JC,H = 147,
1
142 Hz, 2×OMe), 49.4, 47.6 (2 t, JC,H = 127, 128 Hz, C-2, C-4),
45.8, 45.5, 45.1 (3 t, 1JC,H = 128, 130, 126 Hz, C-1, C-3, C-5), 39.7,
1
39.4, 37.6, 37.5 (4 t, JC,H = 123, 127 Hz, C-3Ј, C-3ЈЈ, C-5Ј, C-
5ЈЈ) ppm. MALDI-HR-MS: calcd. for [C33H50N2O8 +H] 603.3645;
found 603.3698.
tinct sets of signals). IR (film): ν = 3350, 2925, 2505, 1450, 1385,
˜
1
1115, 1040, 965 cm–1. H NMR (400 MHz, D2O): δ = 4.84 (br. s,
Synthesis of 22: A catalytic amount of Raney nickel was added to
a solution of 7 (95 mg, 0.147 mmol) in MeOH (1.5 mL), and the
resulting mixture was vigorously stirred under hydrogen (1 atm.).
After 4 h, the mixture was filtered through a pad of Celite and
concentrated in vacuo. Purification of the residue by flash
chromatography (5% MeOH in CH2Cl2) afforded 22 as a colourless
oil (53 mg, 90%, 2:1 ratio for two distinct sets of signals). IR (film):
1.34 H, 6maj-H, 6Јmaj-H), 4.42–4.35 (m, 0.66 H, 6min-H, 6Јmin-H),
3.96–3.80 (m, 2.68 H, 2maj-H, 4maj-H, 2ЈЈmaj-H, 4ЈЈmaj-H), 3.58–3.54
(m, 1.34 H, 2min-H, 4min-H, 2ЈЈmin-H, 4ЈЈmin-H), 3.41, 3.40 (2 s, 1.98
H, 2×OMemin.), 3.27, 3.25 (2 s, 4.02 H, 2×OMemaj.), 3.03–2.98 (m,
0.66 H, 2Јmin-H, 4Јmin-H), 2.83–2.74 (m, 1.34 H, 2Јmaj-H, 4Јmaj-H),
2.1–1.8 (m, 4 H, 3-H2, 3ЈЈ-H2), 1.75–1.30 (m, 6 H, 1Ј-H2, 3Ј-H2, 5Ј-
H2), 1.22–1.08 (m, 4 H, 5-H2, 5ЈЈ-H2) ppm. 13C NMR (100 MHz,
D2O): δ = 101.4, 101.3 (2 d, 1JC,H = 171 Hz, C-6min., C-6Јmin.), 99.4,
ν = 3390, 3350, 2920, 1605, 1450, 1370, 1105, 1025, 960, 925, 870,
˜
735 cm–1. 1H NMR (400 MHz, MeOD): δ = 4.83–4.78 (m, 1.34 H,
1
99.3 (2 d, JC,H = 172 Hz Hz, C-6maj., C-6Јmaj.), 66.0, 65.4, 63.3 (4
6maj-H, 6Јmaj-H), 4.32–4.28 (m, 0.66 H, 6min-H, 6Јmin-H), 4.23–4.08
1
d, JC,H = 140, 142, 141, 141, C-2maj., C-4maj., C-2ЈЈmaj., C-4ЈЈmaj.),
(m, 2 H, 4ЈЈ-H, 6ЈЈ-H), 4.03–3.07 (m, 4 H, 2-H, 4-H, 2Ј-H, 4Ј-H)
3.29 (s, 4.02 H, 2×OMemaj), 3.46, 3.45 (2 s, 1.98 H, 2×OMemin.),
2.10–1.77, 1.28–1.07 (2 m, 8 H, 3-H2, 5-H2, 3Ј-H2, 5Ј-H2), 1.63–
1.52, 1.51–1.42 (2 m, 6 H, 5ЈЈ-H2, 2×1ЈЈЈ-H2), 1.23, 1.17 (2 s, 6 H,
2×Me-2ЈЈ) ppm. 13C NMR (100 MHz, MeOD): δ = 99.9 (s, C-2ЈЈ),
65.9, 65.8, 63.3, 63.1 (4 d, C-2min., C-4min., C-2ЈЈmin., C-4ЈЈmin.), 56.6
1
1
(q, JC,H = 140 Hz, 2×OMemin.), 54.9 (q, JC,H = 143 Hz,
1
2×OMemaj.), 51.8, 51.6 (2 d, JC,H = 138 Hz, C-2Јmaj., C-4Јmaj.),
46.2, 45.0 (2 d, JC,H = 139 Hz, C-2Јmin., C-4Јmin.), 42.3, 41.9 (3 t,
1
C-1Ј, C-3Ј, C-5Ј), 40.2, 40.1 (2 t, C-3min., C-3ЈЈmin.), 39.9, 39.7 (2 t,
1
101.7, 101.6 (2 d, JC,H = 142 Hz, C-6min., C-6Јmin.), 99.5, 99.3 (2
1
C-3maj., C-3ЈЈmaj.), 38.9 (t, C-5min., C-5ЈЈmin.), 37.9 (t, JC,H
=
1
1
d, JC,H = 141 Hz, C-6maj., C-6Јmaj.), 66.3 (d, JC,H = 140 Hz, C-2,
123 Hz, C-5maj., C-5ЈЈmaj.) ppm. ESI-MS: m/z = 363 [M+H].
MALDI-HR-MS: calcd. for [C17H34N2O6 +H] 363.2495; found
363.2485.
1
C-2Ј), 65.4, 64.5 (2 d, JC,H = 136 Hz, C-4ЈЈ, C-6ЈЈ), 63.5, 63.3 (2
1
1
d, JC,H = 137 Hz, C-4, C-4Ј), 55.8, 55.7 (2 q, JC,H = 145 Hz,
1
2×OMe min.), 54.2, 53.9 (2 q, JC,H = 145 Hz, 2×OMemaj), 43.3,
1
42.5, 41,4 (3 t, JC,H = 129, 127, 128 Hz, C-1ЈЈ, C-5ЈЈ), 40.7, 39.1,
1
37.8, 39.0 (4 t, JC,H = 128, 129, 129, 126 Hz, C-3, C-5, C-3ЈЈ, C-
Acknowledgments
5ЈЈ), 29.6, 19.2 (2 q, 1JC,H = 117, 121 Hz, 2×Me-2ЈЈmaj.), 29.5, 19.1
1
(2 q, JC,H = 120, 121 Hz, 2×Me-2ЈЈmin.) ppm. ESI-MS: m/z = 405
This work was supported by the Swiss National Foundation (grant
no. 200020-107532). We thank Martial Rey and Francesco Sepul-
veda for technical help.
[M+H]. C20H36O8 (404.50): calcd. C 59.39, H 8.97; found C 58.45,
H 9.02.
Synthesis of 24: Diol 22 (174 mg, 0.432 mmol) was dissolved in
4 mL of pyridine/Ac2O (1:1) and treated with 10 mg of DMAP
(0.086 mmol, 0.2 equiv.). The resulting mixture was stirred at 25 °C
for 1 h. The mixture was concentrated in vacuo and filtered
through silica gel (3% of MeOH in CH2Cl2) to afford a pale-orange
oil. The resulting diacetate (160 mg, 0.328 mmol) was dissolved in
3 mL of MeOH and treated with 12 mg of p-toluenesulfonic acid
(0.065 mmol, 0.2 equiv.) at 25 °C for 2 h. The mixture was poured
into a satd. aq. solution of NaHCO3 (10 mL) and extracted with
CH2Cl2 (10 mL, 3 times). The combined organic extracts were
dried with MgSO4 and concentrated in vacuo. The crude oil was
dissolved in CH2Cl2 (2 mL) and treated at 0 °C with triethylamine
(266 µL, 1.906 mmol, 9 equiv.) and methanesulfonyl chloride
(62 µL, 0.635 mmol, 3 equiv.). After stirring at 0 °C for 1 h, the
mixture was poured into a satd. aq. solution of NH4Cl (20 mL)
and extracted with EtOAc (20 mL, 3 times). The combined organic
extracts were washed with brine (30 mL), dried with MgSO4 and
concentrated in vacuo. The crude dimesylate was dissolved in DMF
(3.5 mL). Sodium azide (137 mg, 2.118 mmol, 10 equiv.) was added
and the mixture was heated at 60 °C for 12 h. The solution was
poured into water (20 mL) and extracted with EtOAc (20 mL, 3
times). The combined organic extracts were washed with brine
(30 mL), dried with MgSO4 and concentrated in vacuo. The crude
diazide was dissolved in MeOH (3 mL) and treated at 25 °C with
125 mg of K2CO3 (0.903 mmol, 3 equiv.) for 4 h. The mixture was
poured into water (20 mL) and extracted with EtOAc (20 mL, 3
times). The combined organic extracts were washed with brine
(30 mL), dried with MgSO4 and concentrated in vacuo. Purifica-
tion by flash chromatography (3% of MeOH in CH2Cl2) afforded
23 as a colourless oil (66 mg, 37%, 5 steps). Diol 23 (60 mg,
[1] a) P. M. Collins, R. J. Ferrier, Monosaccharides: Their Chemis-
try and Their Role in Natural Products; John Wiley & Sons,
Chichester, 1996; b) A. C. Weymouth-Wilson, Nat. Prod. Rep.
1997, 14, 99; c) H. C. Hang, C. R. Bertozzi, Acc. Chem. Res.
2001, 34, 727–736; d) C. R. Bertozzi, L. L. Kiessling, Science
2001, 291, 2357–2364.
[2] For illustrative examples, see: a) S. Knauer, B. Kranke, L.
Krause, H. Kuntz, Curr. Org. Chem. 2004, 8, 1739–1761; b)
R. J. Ferrier, Carbohydr. Chem. 2003, 34, 118–135; c) T. Pathak,
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Received: March 29, 2006
Published Online: July 10, 2006
Eur. J. Org. Chem. 2006, 3903–3909
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