Minimally competent lewis acid catalysts: Indium(III) and bismuth(III) salts produce rhamnosides (=6-deoxymannosides) in high yield and purity

Article abstract of DOI:10.1002/hlca.201200528

Glycosylation of decan-1-ol (2), (±)-decan-2-ol (3), and (±)-methyl 3-hydroxydecanoate (4) with L-rhamnose peracetate 5 to produce rhamnosides (=6-deoxymannosides) 6, 7, and 8 in the presence of Lewis acids BF₃×Et₂O, Sc(OTf)₃

Full text of DOI:10.1002/hlca.201200528

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Helvetica Chimica Acta – Vol. 95 (2012)
Minimally Competent Lewis Acid Catalysts: Indium(III) and Bismuth(III)
Salts Produce Rhamnosides (¼6-Deoxymannosides) in High Yield and Purity
by Clifford Cossa), Tucker Carroccia), Raina M. Maierb), Jeanne E. Pembertona), and Robin Polt*a)
a) Carl S. Marvel Laboratories, Department of Chemistry and Biochemistry, BIO5, The University of
Arizona, Tucson, AZ 85721, USA (phone: þ 1-520-3702654; fax: þ 1-520-6216322;
e-mail: polt@u.arizona.edu)
b) Department of Soil, Water and Environmental Science, The University of Arizona, Tucson, AZ 85721,
USA
This paper is dedicated to Dieter Seebach for the wonderful science that he has showed us all as a chemist,
and for the kindness he has showed me as a person
Glycosylation of decan-1-ol (2), (ꢀ)-decan-2-ol (3), and (ꢀ)-methyl 3-hydroxydecanoate (4) with l-
rhamnose peracetate 5 to produce rhamnosides (¼6-deoxymannosides) 6, 7, and 8 in the presence of
Lewis acids BF3 · Et2O, Sc(OTf)3, InBr3, and Bi(OTf)3 was studied (Table 1). While the strong Lewis
acids BF3 · Et2O and Sc(OTf)3 were effective as glycosylation promoters, they had to be used in excess;
however, glycosylation required careful control of reaction times and temperatures, and these Lewis
acids produced impurities in addition to the desired glycosides. Enantiomerically pure rhamnosides (R)-1
and (S)-1 (Fig.) were obtained from l-rhamnose peracetate 5 and (ꢀ)-benzyl 3-hydroxydecanoate (9)
via the diastereoisomeric rhamnosides 10 (Table 2; Scheme 3). The much weaker Lewis acids InBr3 and
Bi(OTfl)3 produced purer products in high yield under a wider range of conditions (higher temper-
atures), and were effective glycosylation promoters even when used catalytically (<10% catalyst;
Table 2). We refer to these Lewis acids as ꢀminimally competent Lewis acidsꢁ (cf. Scheme 4).
Introduction. – Earlier studies [1] directed toward the glycosylation of serine and
threonine [2] with readily available sugar peracetates [3] for the efficient production of
O-linked glycopeptides [4 – 6] led us to explore the use of weaker rather than stronger
Lewis acids in conjunction with higher temperatures with these relatively unreactive
per-O-acetylated glycosyl donors [7]. The discovery that the weak Lewis acid InBr3 was
effective led us explore this approach in the synthesis of rhamnolipids [8]. Rademann
and co-workersꢁ synthesis was quite elegant for the production of a rhamnolipid library
[9] but did not provide a robust, scalable approach that could be used to produce larger
amounts for the study of their surfactant properties [10].
We required rhamnoside diastereoisomers, (R)-1 and (S)-1 (Fig.), as well as the
ability to produce various chain lengths at will. These single-chain glycosides are
related to bacterial rhamnolipids [8][9], which are typically produced as mixtures of
various chain lengths [10][11]. Bacterial rhamnolipids, particularly those produced by
Pseudomonas aeruginosa show a great deal of promise for the environmental
remediation of oil spills [12][13] and toxic metals [14][15].
Results. – The first glycosylation reactions were performed with decan-1-ol (2) as a
model glycosyl acceptor and b-lactose peracetate as a model glycosyl donor. Heating
ꢂ 2012 Verlag Helvetica Chimica Acta AG, Zꢃrich

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Figure. Diastereoisomeric glycolipids (rhamnolipid analogues) (R)- and (S)-1
mixtures of the donor and acceptor in a sealed tube (by means of microwaves) in
ClCH2CH2Cl as solvent in the presence of InBr3 or other Lewis acids was used to define
`
reaction conditions (Scheme 1). The classical Zemplen deacylation methodology
(MeONa/MeOH pH ꢁ 9) was used to remove the acetate protecting groups to provide
the nonionic surfactant b-decyl lactoside in 50% yield. Higher temperatures (> 808) or
longer reaction times for the glycosylation resulted in the formation of a-lactoside and
product degradation.
Scheme 1. Synthesis of b-Decyl Lactoside from the Peracetate of b-Lactose
These were the initial conditions used for the synthesis of l-rhamnosides. The
requisite fatty acid was prepared from the corresponding b-keto ester by simple
reduction with NaCNBH3 [16][17], or by enantioselective reduction by means of
Noyoriꢁs method [18]. The b-keto ester in turn was prepared from the appropriate acyl
chloride and Meldrumꢁs acid [19] as depicted in Scheme 2.
l-Rhamnose (¼6-deoxy-l-mannose) was converted to the peracetate donor 5 with
Ac2O and pyridine, and subjected to glycosylation conditions (microwaves) in the
presence of one of three different Lewis acids. Initially, the BF3 · Et2O, Sc(OTf)3 (Tfl ¼
CF3SO2), and InBr3 in ClCH2CH2Cl were examined as promoters in conjunction with
the three acceptors decan-1-ol (2), (ꢀ)-decan-2-ol (3), and methyl (ꢀ)-3-hydroxyde-
canoate (4) to produce glycosides 6, 7, and 8, respectively (Table 1). Other solvent
systems were explored: CH2Cl2/PhMe 1:5; CHCl3, and CCl4 were found to be effective,
but several other solvents were not useful, i.e., in Et2O, THF, and DMF, was formed no
product. Temperatures above 808 resulted in product mixtures.
Further studies indicated that, similar to InBr3, the bismuth(III) salt Bi(OTfl)3 [20]
was also a minimally competent Lewis acid, but with properties that were superior to
InBr3 for these reactions, as shown in Table 2. In addition to being less hygroscopic than

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 2. Synthesis of Benzyl 3-Hydroxydecanoates from Meldrumꢀs Acid
Table 1. Synthesis of Glycosides from l-Rhamnose Peracetate 5 and Decanols 2 – 4 in ClCH2CH2Cl, in the
Presence of Different Lewis Acidsa)
Decanol
Yieldb) [%]
BF3 · Et2O (5.0 equiv.) Sc(OTfl)3 (1.0 equiv.) InBr3 (0.1 equiv.)
Decan-1-ol (2)
52
71
39
33
16
39
50
34
(ꢀ)-Decan-2-ol (3)
Methyl (ꢀ)-3-hydroxydecanoate (4) 43
a) Conditions: 2.2 equiv. of l-rhamnose peracetate 5 and 1 equiv. of decanol 2, 3, or 4 in ClCH2Cl2Cl at
608 in a sealed tube. b) Yield of 6 (from 2), 7 (from 3), and 8 (from 4).
indium(III) compounds, bismuth(III) salts are generally regarded as nontoxic, and are
much cheaper than the corresponding indium(III) salts [21]. Additionally it was
discovered that MeCN was the best solvent for rhamnoside formation [22], and that
conventional reflux conditions with this solvent were ideal. The methyl ester 8 was
replaced by benzyl ester 9 to permit hydrogenolysis and UV monitoring. The minimally
competent Bi(OTf)3 provided higher yields than InBr3, and conventional heating
conditions with MeCN as the solvent was reproducible, forming the rhamnosides 6, 7,
and 10 from decan-1-ol (2), (ꢀ)-decan-2-ol (3), and benzyl (ꢀ)-3-hydroxydecanoate
(9).
Hydrogenolysis of the diastereoisomer mixture of benzyl esters 10 produced a
mixture of acids 11 in which the l-rhamnoside head group functioned as a very effective

Helvetica Chimica Acta – Vol. 95 (2012)
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Table 2. Comparison of Lewis Acids InBr3 and Bi(OTfl)3 in the Glycosylations of l-Rhamnose Peracetate
5 with Decanols 2, 3, or 9 in MeCNa)
Decanol
Yieldb) [%]
InBr3 (0.1 equiv.)
Bi(OTfl)3 (0.1 equiv.)
Decan-1-ol (2)
89
83
38
91
89
60
(ꢀ)-Decan-2-ol (3)
Benzyl (ꢀ)-3-hydroxydecanoate (9)
a) Conditions: 2.2 equiv. of l-rhamnose peracetate 5 and 1 equiv. of 2, 3, or 9 in MeCN under reflux,
2.5 h. b) Yield of 6 (from 2), 7 (from 3), and 10 (from 9).
chiral auxiliary during chromatography (Scheme 3), permitting facile separation of the
`
diastereoisomeric acids (R)-11 and (S)-11. Subsequent Zemplen deacylation of the
purified diastereoisomers provided the corresponding rhamnosides (R)-1 and (S)-1 in
excellent yield and purity.
Scheme 3. Chromatographic Separation of Diasteroisomeric Monolipids 11

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Discussion. – A major benefit of minimally competent Lewis acid is the fact that it
can be used as a true catalyst, rather than stoichiometrically as a promoter of
glycosylation. Stronger Lewis acids will retain the acetate leaving group from the
donor, essentially becoming Brønsted acids as the glycosylation reaction proceeds. The
minimally competent Lewis acids release the acetate to form acetic acid during the
reaction, with concomitant regeneration of the catalyst (Scheme 4). Thus, the use of an
ꢀ H-atom acceptorꢁ such as tetramethylurea [23] is not necessary or even desirable for
such glycosylations.
Scheme 4. Minimally Competent Lewis Acids Releasing the Acetate Moiety to Regenerate the Active
Lewis acid. Stronger Lewis acids retain the acetate to produce strong Brønsted acids.
Discovery of a second minimally competent Lewis acid, Bi(OTfl)3, augers well for
the discovery of more catalysts for glycosylation. It is noteworthy that the use of the
relatively simple and robust sugar peracetates in conjunction with these mild Lewis
acids allows for considerable leeway in the development of glycosylation conditions.
Thus, the use of highly reactive glycosyl donors (e.g., bromides, trichloroacetimidates,
sulfoxides) for use with stoichiometric or even excess amounts of expensive, unstable,
and/or exotic promoters (Agþ, Hg2þ salts, BF3 · Et2O [Me2SSMe](OTfl), etc.), and long
reaction times are no longer required. Although above-described reactions were
performed with 10% Bi(OTfl)3 and nominally dry MeCN so that the reactions go to
completion within a few hours, scrupulously dry conditions permit the use of much
smaller amounts of catalyst. Further experimentation with more complex glycosides,
polysaccharides, and glycolipids is clearly warranted.
Experimental Part
1. General. All glassware was flame-dried prior to reactions, and all reactions were done under Ar.
Microwave: 900 W Emerson MW8992SB microwave oven, purchased from a Target department store.
Flash chromatography (FC): silica gel 60 (SiO2, 200 – 400 mesh; Geduran No. EM-11567-1); Horizon
HPFC system (Biotage, Inc.). HPLC: Varian-Prostar HPLC system, with a Prostar-330 photodiode array
detector and a Phenomenex-Jupiter (250 mm ꢂ 21.2 mm, 15 mm) C18 semi-prep. column. M.p.: uncor-
rected. 1H- and 13C-NMR Spectra: Bruker-DRX-400 (400 MHz), -DRX-500 (500 MHz), and -DRX-600
(600 MHz) spectrometers; in CDCl3, (D6)DMSO, or CD3OD; d in ppm rel. to Me4Si as internal standard,
J in Hz; all NMR spectra were analyzed and interpreted with the MestReNovaꢄ software. ESI-MS:
Thermo-Finnigan LCQ Deca with pos. and neg. detection, MeOH/H2O 1 : 1 solvent system; in m/z
(rel. %).

Helvetica Chimica Acta – Vol. 95 (2012)
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2. Decyl b-Lactoside. A mixture of AcOK (6.56 g, 66.8 mmol) and Ac2O (21 ml, 220 mmol) was
heated under reflux, followed by slow addition of lactose (1.01 g, 2.79 mmol) to the boiling mixture. The
mixture was stirred for 5 min and allowed to cool to r.t., where it was then diluted with CH2Cl2 and
washed with ice-cold H2O, 1% NaHCO3, sat. NaHCO3, and sat. NaCl soln. The org. layer was dried
(MgSO4) and concentrated to a colorless oil which was then dissolved in a minimal amount of CH2Cl2
and recrystallized by addition of Et2O: b-lactose peracetate (58%). White, crystalline solid. M.p. 104 –
1068.
The b-lactose peracetate (1.78 g, 2.62 mmol), decan-1-ol (2; 0.50 ml, 2.62 mmol), and InBr3 (0.093 g,
0.262 mmol) were added to a 50 ml triple-walled resealable vessel (internally threaded with a Teflon
plug), dissolved in ClCH2CH2Cl (3 – 4 ml), and irradiated in a 900 W Emerson-MW8992SB microwave
oven (power level 6) for 2 min. The crude yellow oil was purified b FC (gradient AcOEt/hexanes 1:9 !
1
2 :8 ! 3 :7 ! 4 :6): decyl b-lactoside peracetate (60%). White foam. M.p. 94 – 998. H-NMR (500 MHz,
CDCl3): 5.31 (d, J ¼ 3.2, 1 H); 5.16 (t, J ¼ 9.3, 1 H); 5.07 (dd, J ¼ 10.4, 7.9, 1 H); 4.92 (dd, J ¼ 10.4, 3.4,
1 H); 4.85 (dd, J ¼ 9.5, 8.0, 1 H); 4.49 – 4.38 (m, 3 H); 4.15 – 4.01 (m, 3 H); 3.87 – 3.72 (m, 3 H); 3.56 (ddd,
J ¼ 9.8, 5.0, 1.9, 1 H); 3.41 (dt, J ¼ 9.6, 6.8, 1 H); 2.12 (s, J ¼ 2.9, 3 H); 2.09 (s, J ¼ 7.8, 3 H); 2.06 – 1.97 (m,
12 H); 1.93 (s, J ¼ 5.9, 3 H); 1.58 – 1.45 (m, 2 H); 1.33 – 1.16 (m, 14 H); 0.85 (t, J ¼ 6.9, 3 H). 13C-NMR
(125 MHz, CDCl3): 170.2; 170.2; 170.0; 169.9; 169.6; 169.4; 168.9; 101.0; 100.6; 76.3; 72.9; 72.6; 71.8; 71.0;
70.7; 70.2; 69.2; 66.7; 62.1; 60.8; 31.9; 29.6; 29.5; 29.4; 29.3; 29.3; 25.8; 22.7; 20.8; 20.8; 20.7; 20.6; 20.5;
14.1. ESI-MS (pos.): 815.1 (17, [M þ K]þ), 799.2 (99, [M þ Na]þ), 794.1 (53, [M þ NH4]þ).
The decyl b-lactoside peracetate (2.93 g, 3.77 mmol) was dissolved in dry MeOH (30 ml) under Ar,
and a 25% (wt./v) MeONa/MeOH soln. (0.5 ml) was added dropwise until the soln. reached pH 9 – 10.
The mixture was stirred for 24 h (TLC monitoring) and then neutralized by Dowexꢄ 50WX8 – 100 ion-
exchange resin. The mixture was filtered and the filtrate concentrated: decyl b-lactoside (72%). White
solid. M.p. 140 – 1608 (dec.). 1H-NMR (500 MHz, (D6)DMSO): 6.04 (s, 1 H); 5.84 – 5.31 (m, 4 H); 5.17
(dd, J ¼ 19.1, 7.5, 2 H); 4.73 (dt, J ¼ 6.6, 5.8, 2 H); 4.67 – 4.14 (m, 19 H); 3.99 (t, J ¼ 8.2, 1 H); 3.50 (dt, J ¼
3.6, 1.8, 1 H); 2.37 – 2.13 (m, 14 H); 1.85 (t, J ¼ 6.9, 3 H). 13C-NMR (125 MHz, (D6)DMSO): 103.8; 102.5;
80.8; 75.5; 75.0; 74.8; 73.2; 73.1; 70.6; 68.7; 68.1; 60.6; 60.4; 31.3; 29.3; 29.0; 29.0; 28.9; 28.7; 25.5; 22.1;
14.0. ESI-MS (pos.): 987.0 (100, [2 M þ Na]þ), 964.9 (13, [2 M þ H]þ), 505.4 (12, [M þ Na]þ), 482.9 (10,
[M þ H]þ).
3. Microwave Procedure for Rhamnosides 6 – 8 (Table 1). Rhamnose peracetate 5 (1.2 equiv.),
alcohol (1 equiv.), and Sc(OTf)3 (1 equiv.), InBr3 (0.1 equiv.), or BF3 · Et2O (5 equiv.) were dissolved in
dry ClCH2CH2Cl (1.5 ml) in a flame-dried triple-walled resealable vessel (internally threaded with a
Teflon plug), and the vessel was microwave-irradiated (900 W Emerson MW8992SB) for 2 min on power
level 6. The slightly yellow mixture was neutralized with sat. NaHCO3 soln., the org. layer washed with
H2O, dried (MgSO4), and concentrated, and the obtained oil purified by FC (20% AcOEt/hexanes).
Yields of 6 – 8 in Table 1.
Decyl 6-Dexoy-a-l-mannopyranoside Triacetate (6): Colorless oil. Rf (30% AcOEt/hexanes) 0.64.
1H-NMR (500 MHz, CDCl3): 5.28 (dd, J ¼ 10.1, 3.5, 1 H); 5.20 (dd, J ¼ 3.5, 1.7, 1 H); 5.03 (t, J ¼ 9.9, 1 H);
4.68 (d, J ¼ 1.5, 1 H); 3.84 (dq, J ¼ 9.9, 6.3, 1 H); 3.63 (dt, J ¼ 9.5, 6.8, 1 H); 3.39 (dt, J ¼ 9.6, 6.6, 1 H); 2.12
(s, 3 H); 2.02 (s, 3 H); 1.96 (s, 3 H); 1.59 – 1.53 (m, 2 H); 1.35 – 1.21 (m, 14 H); 1.19 (d, J ¼ 6.3, 3 H); 0.86
(t, J ¼ 6.9, 3 H). 13C-NMR (125 MHz, CDCl3): 170.2; 170.0; 169.9; 97.4; 71.3; 70.0; 69.2; 68.2; 66.2; 31.9;
29.6; 29.5; 29.4; 29.3; 29.3; 26.1; 22.7; 20.9; 20.8; 20.7; 17.4; 14.1.
(1R)- and (1S)-1-Methylnonyl 6-Deoxy-a-l-mannopyranoside Triacetate (7; diastereoisomer mix-
ture 1:1): Colorless oil. Rf (30% AcOEt/hexanes) 0.68. 1H-NMR (500 MHz, CDCl3): 5.28 (dd, J ¼ 10.1,
3.5, 1 H); 5.25 (dd, J ¼ 10.1, 3.5, 1 H); 5.15 – 5.11 (m, 2 H); 5.02 (t, J ¼ 9.9, 1 H); 5.01 (t, J ¼ 10.0, 1 H);
4.79 (d, J ¼ 1.7, 1 H); 4.77 (d, J ¼ 1.7, 1 H); 3.92 (dq, J ¼ 9.8, 6.3, 1 H); 3.89 (dq, J ¼ 9.8, 6.3, 1 H); 3.70 (dt,
J ¼ 11.8, 6.0, 1 H); 3.64 (dt, J ¼ 12.4, 6.1, 1 H); 2.11 (s, 6 H); 2.01 (s, 3 H); 2.01 (s, 3 H); 1.95 (s, 6 H); 1.60 –
1.44 (m, 2 H); 1.44 – 1.30 (m, 2 H); 1.26 (dd, J ¼ 26.5, 8.0, 24 H); 1.16 (d, J ¼ 6.3, 9 H); 1.08 (d, J ¼ 6.1,
3 H); 0.84 (t, J ¼ 6.9, 3 H); 0.84 (t, J ¼ 7.0, 3 H). 13C-NMR (125 MHz, CDCl3): 170.2; 170.1; 170.0; 169.9;
169.9; 97.0; 94.9; 75.8; 73.1; 71.4; 71.2; 70.6; 70.4; 69.2; 69.2; 66.4; 66.2; 36.9; 36.2; 31.8; 31.8; 29.6; 29.5;
29.5; 29.5; 29.2; 29.2; 25.6; 25.3; 22.6; 21.1; 20.9; 20.8; 20.7; 18.9; 17.3; 17.3; 14.1.
Methyl (3R)- and (3S)-3-[(2,3,4-Tri-O-acetyl-6-deoxy-a-l-mannopyranosyl)oxy]decanoate (8; dia-
stereoisomer mixture 1:1): Colorless oil. Rf (pair of diastereoisomers) 0.45 and 0.40. 1H-NMR

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Helvetica Chimica Acta – Vol. 95 (2012)
(500 MHz, CDCl3): 5.21 (d, J ¼ 3.4, 1 H); 5.19 (d, J ¼ 3.4, 1 H); 5.11 (dd, J ¼ 3.4, 1.8, 1 H); 5.07 (dd, J ¼
3.4, 1.8, 1 H); 5.01 (t, J ¼ 9.9, 1 H); 4.99 (t, J ¼ 10.0, 1 H); 4.83 (d, J ¼ 1.5, 1 H); 4.80 (d, J ¼ 1.5, 1 H);
4.10 – 3.97 (m, 2 H); 3.94 – 3.82 (m, 2 H); 3.66 (s, 3 H); 3.65 (s, 3 H); 2.54 (dd, J ¼ 15.3, 8.1, 1 H); 2.50 (dd,
J ¼ 15.5, 7.5, 1 H); 2.44 (dd, J ¼ 15.4, 6.4, 1 H); 2.43 (dd, J ¼ 15.4, 6.9, 1 H); 2.10 (d, J ¼ 2.8, 6 H); 2.00 (d,
J ¼ 3.0, 6 H); 1.93 (d, J ¼ 1.9, 6 H); 1.63 – 1.40 (m, 4 H); 1.36 – 1.17 (m, 16 H); 1.16 (d, J ¼ 6.3, 1 H); 1.15
(d, J ¼ 6.2, 1 H); 0.83 (td, J ¼ 6.9, 3.5, 6 H). 13C-NMR (125 MHz, CDCl3): 171.7; 171.6; 170.1; 170.0; 169.9;
169.9; 169.9; 97.5; 95.9; 76.3; 74.9; 71.1; 70.3; 70.2; 69.1; 69.0; 66.7; 66.6; 51.7; 51.6; 39.9; 39.3; 35.0; 33.3;
31.7; 31.7; 29.4; 29.4; 29.1; 29.1; 25.1; 24.7; 22.6; 22.6; 20.9; 20.9; 20.8; 20.7; 17.2; 17.2; 14.0.
4. Conventional Reflux Procedure for Rhamnosides 6, 7, and 10 (Table 2). To a soln. of rhamnose
peracetate 5 (2.2 equiv.) in dry MeCN, the alcohol (1 equiv.) and either Bi(OTf)3 (0.10 equiv.) or InBr3
(0.10 equiv.) were added. The mixture was refluxed under a Liebig condenser for 2.5 h and then allowed
to cool to r.t. For Bi(OTf)3, the yellow-brown mixture was diluted with CH2Cl2, Celiteꢄ was added, the
mixture filtered, and the filtrate concentrated to a yellow-brown syrup. For InBr3, the yellow mixture was
diluted with CH2Cl2 and neutralized with sat. NaHCO3 soln., and the org. layer washed with H2O, dried
(MgSO4), and concentrated. Purification was achieved by FC (gradient hexanes/AcOEt 0 ! 20%).
Yields of 6, 7, and 10 in Table 2.
Phenylmethyl (3R)- and (3S)-3-[(2,3,4-Tri-O-acetyl-6-deoxy-a-l-mannopyranosyl)oxy]decanoate
(10; diastereoisomer mixture 45 :55): Colorless oil. Rf (30% AcOEt/hexanes) 0.55. 1H-NMR (500 MHz,
CDCl3): 7.36 – 7.27 (m, 10 H); 5.23 (ddd, J ¼ 10.1, 3.4, 1.0, 2 H); 5.14 (dt, J ¼ 4.4, 2.2, 1 H); 5.13 – 5.10 (m,
5 H); 5.02 (td, J ¼ 10.0, 5.9, 2 H); 4.87 (d, J ¼ 1.6, 1 H); 4.83 (d, J ¼ 1.6, 1 H); 4.14 – 4.02 (m, 2 H); 3.95 –
3.86 (m, 2 H); 2.66 – 2.46 (m, 4 H); 2.12 (d, J ¼ 5.9, 6 H); 2.04 – 1.99 (m, 6 H); 1.96 (d, J ¼ 1.5, 6 H); 1.63 –
1.43 (m, 4 H); 1.37 – 1.19 (m, 23 H); 1.18 (d, J ¼ 6.3, 3 H); 1.15 (d, J ¼ 6.3, 3 H); 0.85 (td, J ¼ 6.9, 3.7, 6 H).
13C-NMR (125 MHz, CDCl3): 171.1; 170.9; 170.1; 170.0; 169.9; 135.7; 135.7; 128.5; 128.5; 128.4; 128.2;
128.2; 97.4; 96.2; 76.1; 75.1; 71.1; 70.3; 70.2; 69.1; 69.1; 66.7; 66.7; 66.5; 66.4; 40.2; 39.5; 35.0; 33.4; 31.7;
29.5; 29.4; 29.1; 29.1; 25.1; 24.7; 22.6; 22.6; 20.9; 20.8; 20.7; 17.3; 14.1.
5. (3R)- and (3S)-3-[(2,3,4-Tri-O-acetyl-6-deoxy-a-l-mannopyranosyl)oxy]decanoic Acid ((R)-11
and (S)-11, resp.). To a soln. of 10 (8.57 g, 15.6 mmol) in dry THF (100 ml) at r.t., a small amount of 10%
(wt.) Pd/C was added under Ar. By means of a balloon, the flask was filled with H2 gas (1 atm) and the
mixture stirred vigorously at r.t. for 24 h. Then the mixture was purged with Ar, diluted with CH2Cl2, and
filtered through Celiteꢄ, the filtrate concentrated, and the resulting oil purified by FC (Et2O/hexanes 1:1
with 1% AcOH): (R)-11 (38%) and (S)-11 (33%).
Data of (R)-11: Colorless oil. [a]D ¼ ꢃ30.6 (c ¼ 1.0, CHCl3). Rf (Et2O/hexanes 1:1 with 1% (v/v)
AcOH) 0.26. 1H-NMR (400 MHz, CDCl3): 5.24 (dd, J ¼ 10.1, 3.5, 1 H); 5.12 (dd, J ¼ 3.4, 1.8, 1 H); 5.03 (t,
J ¼ 9.9, 1 H); 4.89 (d, J ¼ 1.8, 1 H); 4.04 (dq, J ¼ 11.7, 5.9, 1 H); 3.93 (dq, J ¼ 9.8, 6.3, 1 H); 2.57 (dd, J ¼
15.8, 7.5, 1 H); 2.49 (dd, J ¼ 15.8, 5.3, 1 H); 2.11 (s, 3 H); 2.03 (s, 3 H); 1.96 (s, 3 H); 1.65 – 1.50 (m, 2 H);
1.32 – 1.22 (m, 10 H); 1.18 (d, J ¼ 6.3, 3 H); 0.89 – 0.84 (m, 3 H). 13C-NMR (100 MHz, CDCl3): 176.2;
170.2; 170.1; 170.1; 97.5; 76.2; 71.1; 70.3; 69.1; 66.8; 39.3; 35.0; 31.7; 29.4; 29.1; 25.1; 22.6; 20.9; 20.8; 20.7;
20.7; 17.3; 14.0.
Data of (S)-11: Clear oil. [a]D ¼ ꢃ47.9 (c ¼ 1.0, CHCl3); Rf (Et2O/hexanes 1:1 with 1% (v/v) AcOH)
0.38. 1H-NMR (400 MHz, CDCl3): 5.23 (dd, J ¼ 10.1, 3.4, 1 H); 5.14 (dd, J ¼ 3.4, 1.8, 1 H); 5.02 (t, J ¼ 9.9,
1 H); 4.82 (d, J ¼ 1.7, 1 H); 4.07 (dq, J ¼ 7.5, 5.9, 1 H); 3.93 (dq, J ¼ 9.9, 6.3, 1 H); 2.63 (dd, J ¼ 15.9, 7.6,
1 H); 2.52 (dd, J ¼ 15.9, 4.8, 1 H); 2.12 (s, 3 H); 2.02 (s, 3 H); 1.96 (s, 3 H); 1.52 (ddd, J ¼ 23.0, 14.2, 5.3,
2 H); 1.32 – 1.21 (m, 10 H); 1.15 (d, J ¼ 6.3, 3 H); 0.87 – 0.82 (m, 3 H). 13C-NMR (101 MHz, CDCl3):
176.7; 170.2; 170.1; 170.0; 96.4; 75.1; 71.1; 70.3; 69.1; 66.8; 39.9; 33.6; 31.7; 29.5; 29.1; 24.8; 22.6; 20.9; 20.8;
20.7; 17.2; 14.0.
6. (3R)- and (3S)-3-(6-Deoxy-a-l-mannopyranosyloxy)decanoic Acid ((R)-1 and (S)-1, resp.). To a
soln. of (R)-11 (5.77g, 12.5 mmol) in dry MeOH (50 ml) at r.t., MeONa was added while stirring to
achieve a pH 9 – 10 (monitoring by a drop of the mixture onto a moistened pH-indicator strip). The
mixture was stirred at r.t. for 3.5 h and then quenched with Dowex Hþ resin. The resin was removed by
filtration and the filtrate concentrated to an oil. No further purification was required. However,
redissolving of the product in a minimal amount of hexanes, followed by filtration, was occasionally
required to remove residual Naþ salts: (R)-1 (99%). Colorless oil. [a]D ¼ ꢃ34.8 (c ¼ 1.0, MeOH). Rf
1
(10% MeOH/CH2Cl2 with 1% (v/v) AcOH) 0.20. H-NMR (400 MHz, CD3OD): 4.75 (d, J ¼ 1.7, 1 H);

Helvetica Chimica Acta – Vol. 95 (2012)
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3.96 – 3.89 (m, 1 H); 3.65 (dd, J ¼ 3.4, 1.7, 1 H); 3.61 – 3.53 (m, 1 H); 3.51 (dd, J ¼ 9.5, 3.4, 1 H); 3.29 – 3.24
(m, 1 H); 2.34 (qd, J ¼ 15.0, 6.4, 2 H); 1.54 – 1.43 (m, 2 H); 1.26 – 1.17 (m, 10 H); 1.14 (d, J ¼ 6.3, 3 H);
0.80 (dd, J ¼ 7.9, 6.0, 3 H). 13C-NMR (100 MHz, CD3OD): 176.2; 101.6; 76.9; 73.9; 72.7; 72.4; 70.2; 41.2;
36.4; 33.0; 30.7; 30.3; 26.3; 23.7; 17.9; 14.4. ESI-MS (neg.): 334.1 (12, M–), 333.1 (99, [M ꢃ H]–).
Glycolipid (S)-1 was obtained in the same fashion: Yield 99%. Colorless oil. [a]D ¼ ꢃ47.0 (c ¼ 1.0,
MeOH). Rf (10% MeOH/CH2Cl2 with 1% (v/v) AcOH) 0.25. 1H-NMR (400 MHz, CD3OD): 4.66 (d, J ¼
1.7, 1 H); 3.93 (dq, J ¼ 7.5, 5.7, 1 H); 3.62 (dd, J ¼ 3.4, 1.7, 1 H); 3.58 – 3.45 (m, 2 H); 3.20 (t, J ¼ 9.5, 1 H);
2.33 (ddd, J ¼ 20.4, 14.8, 6.6, 2 H); 1.42 (dt, J ¼ 9.1, 6.2, 2 H); 1.21 – 1.13 (m, 10 H); 1.09 (d, J ¼ 6.2, 3 H);
0.77 – 0.73 (m, 3 H). 13C-NMR (100 MHz, CD3OD): 176.5; 100.3; 75.9; 74.0; 72.7; 72.3; 70.1; 42.2; 34.5;
33.0; 30.7; 30.3; 25.9; 23.7; 17.9; 14.4. ESI-MS (neg.): 334.1 (12, Mꢃ), 333.1 (99, [M ꢃ H]–).
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Received September 14, 2012