A formal, stereoselective synthesis of the natural tetrahydropyran derivative ophiocerin D

Article abstract of DOI:10.1016/j.tetasy.2010.01.013

A short, formal stereoselective synthesis of the naturally occurring tetrahydropyran derivative ophiocerin D is reported. The four stereocenters of the molecule were created with the aid of two Sharpless asymmetric dihydroxylations.

Full text of DOI:10.1016/j.tetasy.2010.01.013

Tetrahedron: Asymmetry 21 (2010) 425–428
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
A formal, stereoselective synthesis of the natural tetrahydropyran derivative
ophiocerin D
a
a
b
Julián Paños a, Juan Murga a, , Eva Falomir , Miguel Carda , J. Alberto Marco
*
a Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, 12071 Castellón, Spain
b Depart. de Q. Orgánica, Univ. de Valencia, 46100 Burjassot, Valencia, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
A short, formal stereoselective synthesis of the naturally occurring tetrahydropyran derivative ophiocerin
D is reported. The four stereocenters of the molecule were created with the aid of two Sharpless asym-
metric dihydroxylations.
Received 9 January 2010
Accepted 21 January 2010
Available online 1 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
metric dihydroxylation,9 hydroxyl protection, and ester reduction.
Compound B in turn was to be prepared from commercially avail-
The tetrahydropyran derivatives ophiocerins A-D 1–4 were iso-
lated in 2005 by Gloer et al. from the freshwater aquatic fungus
Ophioceras venezuelense.1 Aside from containing an additional ste-
reocenter, compound 4 differs from compounds 1–3 in having one
of its free hydroxyl groups esterified with cis-crotonic acid. The
presence of this acid moiety is unusual, even though it has been
reported as a component of trichothecin and trichothecinols A–C
isolated from Trichothecium roseum,2 as well as in a trichothecinol
of plant origin3 and in isocrotonylpterosin B isolated from the
bracken fern Pteridium aquilinum (Fig. 1).4
able ethyl sorbate via regioselective asymmetric dihydroxylation9
and hydroxyl protection.
OH
OH
OH
OH
OH
O
O
2
1
OH
OH
Ophiocerins have attracted the attention of the synthetic com-
munity. Seven syntheses of these compounds have been reported
in the last two years; one synthesis of ophiocerin A5 and two syn-
theses each of ophiocerins B,5,6 C,6,7 and D.8 Most of these synthe-
ses used commercial sugars as the starting materials, although one
used a chiral epoxide prepared through catalytic kinetic resolution
of a racemate.
4
3
O
OH
5
O
2
6
O
3
O
1
4
Figure 1. Structures of ophiocerins A–D 1–4.
The first reported synthesis8a of ophiocerin D started from
D
-xylose and arrived at the natural compound in an overall yield
OH
HO
of less than 1%. The other synthesis had -galactose as the chiral
D
OMOM
OMOM
O
starting material and an overall yield of about 6% was obtained.8b
An advanced intermediate in the first synthesis was tetrahydropy-
ran 5, obtained from the sugar precursor in 14 steps.8a Compound 5
was then converted into 4 in three further steps (O-acylation with
2-butynoic acid, triple bond hydrogenation, and cleavage of the
two MOM groups) (Scheme 1).
OH
HO
3 steps
14 steps
4
OH
O
D-xylose
5
Scheme 1. Key transformations in a previous synthesis of 4.
Our synthesis follows the retrosynthetic concept depicted in
Scheme 2 and intercepts the previous synthesis8a in the aforemen-
tioned tetrahydropyran derivative 5. Cleavage of the indicated C–O
bond via intramolecular nucleophilic substitution leads to mesy-
late A, easily referred to enoate B (P = protecting group) via asym-
2. Results and discussion
Scheme 3 depicts the details of the synthetic sequence. Cyclic
carbonate 6 was obtained in two steps from ethyl sorbate according
to the reported procedure.10 The palladium-catalyzed nucleophilic
opening11 of the allylic carbonate fragment by p-methoxyphenol
* Corresponding author. Tel.: +34 964 728243; fax: +34 964 728214.
E-mail address: jmurga@qio.uji.es (J. Murga).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.01.013

426
J. Paños et al. / Tetrahedron: Asymmetry 21 (2010) 425–428
OH
O
3. Conclusions
OMOM
OMOM
O
OH
HO
A formal stereoselective synthesis of the fungal metabolite oph-
iocerin D has been achieved. The synthetic sequence is more effi-
cient in terms of the chemical yield of intermediate 5 than the
previous synthesis of the same compound8a (10 steps and 25%
overall yield from ethyl sorbate versus 14 steps and 2.2% overall
O
O
5
4
OMOM
OMOM
OH OMOM
yield from
compared directly with the second total synthesis of ophiocerin
D8b (14 steps from
-galactose and 6.3% overall yield of 4) but, if
D-xylose). Obviously, our formal synthesis cannot be
PO
OMs
OP OMOM
D
OH OMs
we assume the same yields as those obtained by Sharma and
Damera in the last three steps of the sequence 5?4, we would still
have an overall yield of 10.5% in the natural compound.
A
OH
CO2Et
COOEt
Ethyl sorbate
Scheme 2. Retrosynthetic analysis of 4.
OP
4. Experimental
4.1. General
B
1H/13C NMR spectra were measured at 500/125 MHz in CDCl3
solution at 30 °C. The signals of the deuterated solvent (CDCl3)
were taken as the reference (the singlet at d 7.25 for 1H NMR and
the triplet centered at 77.00 ppm for 13C NMR data). The multiplic-
ities of the 13C NMR signals were determined with the DEPT pulse
sequence. Mass spectra were in most cases run in the electrospray
(ESMS) mode. IR data are given only for compounds with relevant
functions (OH, C@O) and were recorded as oily films on NaCl plates
(oils) or as KBr pellets (solids). Optical rotations were measured at
25 °C. Reactions which required an inert atmosphere were carried
out under N2 with flame-dried glassware. THF was freshly distilled
from sodium-benzophenone ketyl. Dichloromethane was freshly
distilled from CaH2. Hexane was distilled from sodium wire. Com-
mercially available reagents were used as received. Unless detailed
otherwise, ‘work-up’ means pouring the reaction mixture into
brine, followed by extraction with the solvent indicated in paren-
thesis. If the reaction medium was acidic, an additional washing
with 5% aq NaHCO3 was performed. If the reaction medium was
basic, an additional washing with aq NH4Cl was performed. New
washing with brine, drying over anhydrous Na2SO4, and elimina-
tion of the solvent under reduced pressure were followed by chro-
PMPOH,
Pd0 cat.
(98%)
COOEt
COOEt
ref. 10
O
O
O
Ethyl sorbate
6
OR
OR
TBSO
AD-mix-α
COOEt
COOEt
89%
OPMP
R = H
PMPO
OR
MOMCl,
DIPEA, RT
TBSOTf, 2,6-lut,
0 °C (93%)
9 R = H
7
8
10 R = TBS
R = TBS
OMOM
TBSO
1: MsCl, Et3N,
DMAP, 0 °C
DIBAL, hexane, 0 °C
(70% overall from 9)
OH
OMOM
2: TBAF, RT (70%
overall from 11)
PMPO
11
matography on a silica gel column (60–200 lm) and elution with
the indicated solvent mixture. Where solutions were filtered
through a Celite pad, the pad was additionally washed with the
same solvent used, and the washings incorporated to the main or-
ganic layer.
OMOM
OMOM
OMOM
RO
PMPO
OMOM
O
OMs
O
CAN, aq MeCN
0 °C (80%)
12 R = PMP
R = H
5
4.2. Ethyl (2E,4R,5R)-5-hydroxy-4-(4-methoxyphenoxy)hex-2-
enoate, 7
Scheme 3. Abbreviations and acronyms: PMP, p-methoxyphenyl; TBS, tert-butyl-
dimethylsilyl; lut, lutidine; MOM, methoxymethyl; DIPEA, N,N-diisopropyl ethyl-
amine; CAN, cerium ammonium nitrate.
Carbonate 6 (800 mg, 4 mmol) was dissolved under N2 in dry
CH2Cl2 (15 mL) and was treated with Pd2(dba)3ÁCHCl3 (40 mg,
0.04 mmol), triphenylphosphine (21 mg, 0.08 mmol), triethyl-
amine (560 lL, 4 mmol), and p-methoxyphenol (990 mg, 8 mmol).
The reaction mixture was then stirred at reflux for 1 h. Work-up
(extraction with CH2Cl2) and column chromatography on silica
afforded conjugated ester 7 (B, P = PMP). Silylation to 8 followed by
asymmetric Sharpless dihydroxylation using AD-mix-a9 furnished
a
,b-dihydroxy ester 9.11 Protection of the two hydroxyl groups as
gel (hexanes–EtOAc, 8:2) yielded 7 (1.1 g, 98%). Oil, [
a
]
D = À58.8
(c 1, CHCl3), lit.11b for the enantiomer, [
a]
D = +46.9 (c 2, CH2Cl2);
their MOM derivatives12 followed by reduction of the ester group
of 10 afforded alcohol 11. Mesylation of the hydroxyl group of the
latter compound followed by treatment of the crude mesylate (A,
P = PMP) with TBAF caused cleavage of the silyl group followed by
in situ intramolecular nucleophilic displacement of the mesyl moi-
ety to yield tetrahydropyran 12. Selective cleavage of the PMP
group13 provided 5, which had spectroscopic properties matching
with those reported by Sharma and Damera8a for their advanced
synthetic intermediate (see Section 4).
1H NMR d 6.92 (1H, dd, J = 15.5, 5.3 Hz), 6.85–6.75 (4H, m), 6.05
(1H, dd, J = 15.5, 1.5 Hz), 4.45 (1H, td, J = 5.5, 1.5 Hz), 4.18 (2H,
m), 3.94 (1H, apparent quint, J ꢀ 6 Hz), 3.75 (3H, s), 2.70 (1H, br
s, OH), 1.27 (3H, t, J = 7.5 Hz, overlapping a second methyl signal,
3H, d, J = 6.5 Hz); 13C NMR d 165.7, 154.6, 151.7 (C), 143.5, 124.3,
117.3 (Â2), 114.7 (Â2), 83.1, 69.6 (CH), 60.7 (CH2), 55.7, 18.4,
14.1 (CH3); IR mmax (cmÀ1) 3480 (br, OH), 1717 (C@O); ESMS m/z
303.1211 (M+Na+). Calcd for C15H20O5Na, 303.1208.

J. Paños et al. / Tetrahedron: Asymmetry 21 (2010) 425–428
427
4.3. Ethyl (2E,4R,5R)-5-(tert-butyldimethylsilyloxy)-4-(4-methoxy
phenoxy)hex-2-enoate, 8
solution in hexane, 3 mmol). The reaction mixture was then stirred
for 1 h at 0 °C. After this time, MeOH was added (1 mL), with sub-
sequent stirring for 1 h. Work-up (extraction with EtOAc) and col-
umn chromatography of the residue on silica gel (hexanes–EtOAc,
Alcohol 7 (840 mg, 3 mmol) was dissolved under N2 in dry CH2Cl2
(15 mL), cooled to 0 °C, and treated sequentially with 2,6-lutidine
7:3) provided 11 (332 mg, 70% overall from 9). Oil, [a]D = +15 (c
(580
l
L, 5 mmol)and TBSOTf(1 mL, ca. 4.5 mmol). Thereactionmix-
0.86, CHCl3); 1H NMR d 6.87 (2H, br d, J ꢀ 9 Hz), 6.78 (2H, br d,
J ꢀ 9 Hz), 4.87 (1H, d, J = 6.8 Hz), 4.65 (1H, d, J = 6.8 Hz), 4.36 (1H,
d, J = 7 Hz), 4.29 (1H, dd, J = 6.8, 3.5 Hz), 4.24 (1H, qd, J = 6.5,
3.5 Hz), 4.13 (1H, d, J = 7 Hz), 4.04 (1H, dd, J = 6.8, 2.5 Hz), 3.85–
3.70 (3H, br m), 3.75 (3H, s), 3.50 (1H, br s, OH), 3.42 (3H, s),
3.33 (3H, s), 1.28 (3H, d, J = 6.5 Hz), 0.88 (9H, s), 0.09 (3H, s), 0.03
(3H, s); 13C NMR d 153.9, 153.1, 18.2 (C), 116.4 (Â2), 114.6 (Â2),
82.0, 80.7, 77.4, 68.2 (CH), 98.1, 97.9, 63.5 (CH2), 56.4, 55.8, 55.7,
ture was then stirred for 1 h at room temperature and worked up
(extractionwithCH2Cl2). Columnchromatographyonsilicagel(hex-
anes–EtOAc, 9:1) provided 8 (1.1 g, 93%). Oil, [a]D = +8.8 (c 1, CHCl3),
lit.11 for the enantiomer, [
a
]
D = À15 (c 1, CHCl3); 1H NMR d 7.03 (1H,
dd, J = 15.5, 4.7 Hz), 6.85–6.75 (4H, m), 6.06 (1H, dd, J = 15.5, 1.5 Hz),
4.59 (1H, td, J = 5, 1.5 Hz), 4.19 (2H, m), 4.06 (1H, apparent quint,
J ꢀ 6 Hz), 3.77 (3H, s), 1.28 (3H, t, J = 7 Hz), 1.18 (3H, d, J = 6.2 Hz),
0.90 (9H, s), 0.10 (3H, s), 0.07 (3H, s); 13C NMR d 166.1, 154.2,
152.0, 18.1 (C), 144.2, 123.3, 116.9 (Â2), 114.7 (Â2), 81.7, 69.7
(CH), 60.4 (CH2), 55.7, 25.7 (Â3), 19.0, 14.2, À4.7, À4.8 (CH3); IR mmax
(cmÀ1) 1722 (C@O); ESMS m/z 417.2079 (M+Na+). Calcd for
C21H34O5SiNa, 417.2073.
25.9 (Â3), 20.7, À3.7, À4.0 (CH3); IR
m
max 3480 (br, OH) cmÀ1; ESMS
m/z 497.2550 (M+Na+). Calcd for C23H42O8SiNa, 497.2547.
4.7. (2R,3S,4R,5S)-4,5-Bis(methoxymethoxy)-3-(4-methoxy
phenoxy)-2-methyltetrahydropyran, 12
4.4. Ethyl (2R,3R,4R,5R)-5-(tert-butyldimethylsilyloxy)-2,3-
Alcohol 11 (190 mg, 0.4 mmol) was dissolved under N2 in dry
CH2Cl2 (7 mL), cooled to 0 °C, and treated with mesyl chloride
dihydroxy-4-(4-methoxyphenoxy)hexanoate, 9
(37
lL, 0.48 mmol), DMAP (10 mg, 0.08 mmol), and triethylamine
Ester 8 (474 mg, 1.2 mmol) was dissolved at 0 °C in a mixture of
(85
lL, 0.6 mmol). The resulting solution was stirred at 0 °C for
tert-BuOH (3 mL) and water (3 mL). AD-mix-a (1.7 g) and Me-
2 h. Work-up (extraction with CH2Cl2) and removal of all volatiles
under reduced pressure afforded an oily material which was used
as such in the next step.
SO2NH2 (115 mg, 1.2 mmol) were then added. The reaction mix-
ture was then stirred for 18 h at 0 °C. After this time, Na2SO3
(0.65 g) was added, with subsequent stirring for 45 min. Work-
up (extraction with EtOAc) and column chromatography on silica
gel (hexanes–EtOAc, 8:2) furnished dihydroxy ester 9 (457 mg,
89%) as a single diastereoisomer. Its enantiomeric purity was esti-
The above-mentioned crude mesylate was dissolved in dry THF
(2 mL) and treated under N2 with TBAF trihydrate (190 mg,
0.6 mmol). The solution was stirred at rt for 16 h. After removal
of all volatiles under reduced pressure, the residue was chromato-
graphed on silica gel (hexanes–EtOAc, 1:1) to yield 12 (96 mg, 70%
mated to be ca. 96% by HPLC. Oil, [a]
D = +19.5 (c 1, CHCl3), lit.11 for
the enantiomer, [
a
]
D = À18 (c 1, CHCl3); 1H NMR d 6.95 (2H, br d,
overall from 10). Oil, [
a]
D = À17.3 (c 0.9, CHCl3); 1H NMR d 6.99
J ꢀ 9 Hz), 6.83 (2H, br d, J ꢀ 9 Hz), 4.40–4.20 (6H, br m), 4.15 (1H,
br s, OH), 3.78 (3H, s), 3.10 (1H, d, J = 9 Hz, OH), 1.37 (3H, d,
J = 6.4 Hz), 1.33 (3H, t, J = 7.2 Hz), 0.89 (9H, s), 0.08 (3H, s), 0.07
(3H, s); 13C NMR d 173.5, 154.7, 151.7, 17.9 (C), 117.6 (Â2), 114.8
(Â2), 76.6, 72.2, 70.5, 68.6 (CH), 61.7 (CH2), 55.7, 25.7 (Â3), 17.0,
(2H, br d, J ꢀ 9 Hz), 6.79 (2H, br d, J ꢀ 9 Hz), 4.83 (1H, d,
J = 6.4 Hz), 4.70–4.65 (2H, m), 4.63 (1H, d, J = 6.8 Hz), 4.37 (1H, br
d, J = 3 Hz), 4.19 (1H, dd, J = 11, 5.3 Hz), 4.12 (1H, m), 3.77 (3H, s),
3.72 (1H, dd, J = 9.3, 3 Hz), 3.64 (1H, br q, J = 6.4 Hz), 3.37 (3H, s),
3.28 (1H, dd, J = 11, 10 Hz), 3.23 (3H, s), 1.29 (3H, d, J = 6.4 Hz);
13C NMR d 154.7, 154.3 (C), 118.1 (Â2), 114.5 (Â2), 79.7, 79.6,
74.8, 73.6 (CH), 97.4, 96.4, 69.2 (CH2), 55.7 (Â2), 55.5, 17.5 (CH3);
ESMS m/z 365.1573 (M+Na+). Calcd for C17H26O7Na, 365.1576.
14.2, À4.9, À5.2 (CH3); IR mmax 3470 (br, OH), 1736 (C@O) cmÀ1
FAB MS m/z 429.2313 (M+H+). Calcd for C21H37O7Si, 429.2308.
;
4.5. Ethyl (2R,3S,4R,5R)-5-(tert-butyldimethylsilyloxy)-2,3-
bis(methoxymethoxy)-4-(4-methoxyphenoxy) hexanoate, 10
4.8. (2R,3S,4S,5S)-4,5-Bis(methoxymethoxy)-2-methyl
Alcohol 9 (429 mg, 1 mmol) was dissolved under N2 in dry CH2Cl2
tetrahydropyran-3-ol, 5
(20 mL), cooled to 0 °C, and treated with MOM chloride (760 lL,
10 mmol) and DIPEA (2.6 mL, 15 mmol). The resulting solution
was subsequently stirred at room temperature for three days.
Work-up (extraction with CH2Cl2) and filtration on silica gel (hex-
anes–EtOAc, 7:3) afforded compound 10 sufficiently pure for the
next step. An aliquot was carefully purified for analytical purposes.
Compound 12 (55 mg, 0.16 mmol) was dissolved in a 4:1
MeCN–H2O mixture (2 mL). After cooling to 0 °C, CAN (175 mg,
0.32 mmol) was added, with subsequent stirring for 10 min at
0 °C. Work-up (extraction with EtOAc) and column chromatogra-
phy on silica gel (hexanes–AcOEt, 3:7) gave 5 (30 mg, 80%). Oil,
Oil, [
a]
D = +2(c 1.3, CHCl3);1H NMRd 6.90(2H, brd, J ꢀ 9 Hz), 6.79
[a
]
D = À6.2 (c 1.7, CHCl3), lit.8a
[
a]
D = À2.7 (c 2, CHCl3); 1H NMR d
(2H, br d, J ꢀ 9 Hz), 4.80 (1H, d, J = 6.8 Hz), 4.65 (1H, d, J = 6.8 Hz),
4.48 (1H, d, J = 6.8 Hz), 4.36 (1H, dd, J = 6.8, 2.5 Hz), 4.32 (1H, d,
J = 6.8 Hz), 4.31 (1H, d, J = 2.5 Hz), 4.30–4.20 (4H, br m), 3.76 (3H,
s), 3.36 (3H, s), 3.30 (3H, s), 1.30 (3H, t, J = 7 Hz), 1.26 (3H, d,
J = 6.4 Hz), 0.90 (9H, s), 0.10 (3H, s), 0.04 (3H, s); 13C NMR d 171.0,
154.0, 153.0, 18.2 (C), 116.7 (Â2), 114.6 (Â2), 80.4, 78.7, 76.6, 68.2
(CH), 98.0, 97.7, 60.9 (CH2), 56.6, 56.5, 55.7, 25.9 (Â3), 20.7, 14.1,
À3.7, À4.2 (CH3); IR mmax 1751 (C@O) cmÀ1; ESMS m/z 539.2655
(M+Na+). Calcd for C25H44O9SiNa, 539.2652.
4.84 (1H, d, J = 6.7 Hz), 4.80 (1H, d, J = 6.7 Hz), 4.75 (1H, d,
J = 6.6 Hz), 4.67 (1H, d, J = 6.6 Hz), 4.10 (1H, dd, J = 11.3, 5.4 Hz),
3.90 (1H, br td, J ꢀ 10, 5.5 Hz), 3.84 (1H, br s), 3.60 (1H, dd,
J = 9.5, 3 Hz), 3.52 (1H, br q, J = 6.4 Hz), 3.44 (3H, s), 3.36 (3H, s),
3.20 (1H, dd, J = 11, 10 Hz), 2.30 (1H, br s, OH), 1.31 (3H, d,
J = 6.4 Hz); 13C NMR d 80.0, 74.5, 72.8, 71.2 (CH), 97.1, 96.3, 68.9
(CH2), 55.7, 55.5, 16.7 (CH3); IR mmax 3470 (br, OH) cmÀ1; ESMS
m/z 259.1154 (M+Na+). Calcd for C10H20O6Na, 259.1158. The 1H
NMR data of our compound 5 match reasonably well with those
of the synthetic compound with the same structure8a but the lower
resolution of the published 1H NMR data (at 200 MHz) do not per-
mit an accurate comparison with our 500 MHz spectrum. The 13C
NMR data show a much better coincidence, even though the
authors have omitted the carbon signal at about 72.8 ppm.
4.6. (2S,3R,4R,5R)-5-(tert-Butyldimethylsilyloxy)-2,3-
bis(methoxymethoxy)-4-(4-methoxyphenoxy)hexan-1-ol, 11
The above-mentioned crude 10 was dissolved in dry hexane
(15 mL) and treated at 0 °C under N2 with DIBAL (3 mL of a 1 M

428
J. Paños et al. / Tetrahedron: Asymmetry 21 (2010) 425–428
5. Lee, D.-M.; Kang, H.-Y. Bull. Korean Chem. Soc. 2008, 29, 1671–1672.
Acknowledgments
6. Yadav, J. S.; Lakshmi, P. N.; Harshavardhan, S. J.; Reddy, B. V. S. Synlett 2007,
1945–1947.
Financial support has been granted by the Spanish Ministry of
Education and Science (Projects CTQ2005-06688-C02-01/02), and
by the Consellería dEmpresa, Universitat i Ciencia de la Generalitat
Valenciana (Projects GV05/52, ACOMP06/006 and ACOMP06/008).
J.P. thanks the University of Castellón for a pre-doctoral fellowship.
7. Lee, D.-M.; Lee, H.; Kang, H.-Y. Bull. Korean Chem. Soc. 2008, 29, 535–536.
8. (a) Sharma, G. V. M.; Damera, K. Tetrahedron: Asymmetry 2008, 19, 2092–2095;
(b) Lee, D.-M.; Kang, H.-Y. Bull. Korean Chem. Soc. 2009, 30, 1929–1930.
9. (a) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94,
2483–2547; (b) Markó, I. E.; Svendsen, J. S.. In Comprehensive Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 2000;
Vol. 2,. Chapter 20.
´
10. Garaas, S. D.; Hunter, T. J.; O’Doherty, G. A. J. Org. Chem. 2002, 67, 2682–2685.
11. (a) Gao, D.; O’Doherty, G. A. J. Org. Chem. 2005, 70, 9932–9939; (b) Ahmed, M.
M.; O’Doherty, G. A. Carbohydr. Res. 2006, 341, 1505–1521. The reaction
sequence reported in these papers is enantiomeric to our sequence
6?7?8?9.
References
1. Reátegui, R. F.; Gloer, J. B.; Campbell, J.; Shearer, C. A.. J. Nat. Prod. 2005, 68,
701–705.
2. Iida, A.; Konishi, K.; Kubo, H.; Tomioka, K.; Tokuda, H.; Nishino, H. Tetrahedron
Lett. 1996, 37, 9219–9220.
12. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 4th ed.; John
Wiley and Sons: Hoboken, 2007. pp 30–38.
3. Loukaci, A.; Kaiser, O.; Bindseil, K.-U.; Siems, K.; Frevert, J.; Abreu, P. J. Nat. Prod.
2000, 63, 52–56.
13. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 4th ed.; John
Wiley and Sons: Hoboken, 2007. pp 100–101.
4. Fukuoka, M.; Kuroyanagi, M.; Toyama, M.; Yoshihira, K.; Natori, S. Chem. Pharm.
Bull. 1972, 20, 2282–2285.