Total synthesis of (+)-valienamine and (-)-1-epi-valienamine via a highly diastereoselective allylic amination of cyclic polybenzyl ether using chlorosulfonyl isocyanate

Article abstract of DOI:10.1016/j.tet.2013.09.098

The total synthesis of (+)-valienamine and (-)-1-epi-valienamine was concisely accomplished from readily available d-glucose via a highly diastereoselective amination of chiral benzylic ether using chlorosulfonyl isocyanate, intramolecular olefin metathesis, and diastereoselective reduction of cyclic enone using l-Selectride as the key steps.

Full text of DOI:10.1016/j.tet.2013.09.098

Tetrahedron 69 (2013) 10384e10390
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Total synthesis of (þ)-valienamine and (ꢀ)-1-epi-valienamine via
a highly diastereoselective allylic amination of cyclic polybenzyl
ether using chlorosulfonyl isocyanate
Qing Ri Li, Seung In Kim, Sook Jin Park, Hye Ran Yang, A Reum Baek, In Su Kim,
*
Young Hoon Jung
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 July 2013
Received in revised form 24 September 2013
Accepted 27 September 2013
Available online 5 October 2013
The total synthesis of (þ)-valienamine and (ꢀ)-1-epi-valienamine was concisely accomplished from
readily available
D-glucose via a highly diastereoselective amination of chiral benzylic ether using
chlorosulfonyl isocyanate, intramolecular olefin metathesis, and diastereoselective reduction of cyclic
enone using -Selectride as the key steps.
L
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Valienamine
Chlorosulfonyl isocyanate
Amination
Asymmetric
Carbasugar
1. Introduction
amylostatins, adiposins, salbostatin, and acarviosin.9 In particular,
acarbose (4) is known as a highly potent inhibitor of a-glucosidases
Glycosidases are involved in a wide range of important bi-
ological processes, such as intestinal digestion, post-translational
processing of glycoproteins, and lysosomal catabolism of glyco-
conjugates.1 Thus, glycosidase inhibitors have received much at-
tention for the treatment of diabetes,2 viral infections,3 malaria,4
and cancer.5 The majority of these inhibitors are azasugars, in
which an oxygen atom in a monosaccharide is replaced by a nitro-
gen atom. Azasugars are often found in natural plants and micro-
organisms. While these azasugars have been extensively studied,
the development of carbasugars as glycosidase inhibitors has re-
ceived little attention.
in the human digestive tract.10 Consequently, acarbose can delay
the breakdown of ingested carbohydrates and control the re-
sorption of glucose from the intestines. Acarbose (GlucobayÔ) is
currently used as an anti-diabetic drug for the treatment of type II
diabetes mellitus (Fig. 1).
Due to the unique structural feature and interesting biological
property, a number of efforts have been devoted to the de-
velopment of various approaches for the efficient synthesis of
(þ)-valienamine (1). Paulsen et al. reported the first synthesis of 1
starting from L-quebrachitol via Mitsunobu-type inversion of an
allylic hydroxyl group to an azido group.11 Since the pioneering
work of Paulsen, several approaches have been attempted re-
garding the preparation of (þ)-valienamine (1).12e15 Given the
(þ)-Valienamine (1) is a polyhydroxylated unsaturated carba-
sugar that was first isolated from microbial degradation of
validoxylamine
A
(3) with Pseudomonas denitrificans in
structural relationship of (þ)-valienamine with carbohydrates,12
a-
1972.6 Later, it was derived from degradation of validoxylamine
A with Flavobacterium saccharophilum7 or from NBS-mediated
selective cleavage of CeN bond in validoxylamine A or its de-
rivatives.8 (þ)-Valienamine is also an essential core unit in many
kinds of pseudo-oligosaccharides, e.g., acarbose, validamycins,
amino acids,13 and (ꢀ)-quinic acid,14 it is not surprising that most
syntheses use these compounds as starting materials. The chiral
pool approach can be extremely attractive if nature happens to
provide an abundant supply of an inexpensive starting material
appropriate for the synthetic target. One of other syntheses relies
on a series of DielseAlder reactions to generate a cyclohexene
framework.15
In a recent example using a carbohydrate as a chiral pool, Yan and
co-workers reported the total synthesis of 1 from D-tartaric acid
* Corresponding author. Tel.: þ82 31 290 7711; fax: þ82 31 292 8800; e-mail
address: yhjung@skku.edu (Y.H. Jung).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.09.098

Q.R. Li et al. / Tetrahedron 69 (2013) 10384e10390
10385
OH
HO
OH
OH
HO
HO
HO
HO
OH
OH
HO
HO
N
H
OH
OH
NH2
NH2
OH HO
(+)-valienamine (1)
OH
(-)-1-epi-valienamine (2)
validoxylamine A (3)
OH
OH
Me
O
O
O
HO
HO
N
H
O
O
OH
OH HO
OH HO
OH HO
OH
acarbose (4)
Fig. 1. Structures of (þ)-valienamine (1), (ꢀ)-1-epi-valienamine (2), validoxylamine A, (3) and acarbose (4).
through iodine-promoted cyclization of an unsaturated carbon-
imidothioate for the diastereoselective installation of amine and
hydroxyl units.12e In another example using a chiral pool, Kim et al.
described the asymmetric total synthesis of 1 using readily available
herein describe an asymmetric total synthesis of (þ)-valienamine
(1) and its 1-epimer 2 starting from commercially available
glucose via highly regioselective and diastereoselective allylic
amination of cyclic polybenzyl ethers using chlorosulfonyl iso-
cyanate, intramolecular olefin metathesis followed by diaster-
D
-
D-glucose as a starting material via ring-closing metathesis followed
by diastereoselective addition of an azido group under Mitsunobu
conditions.12c In a representative example of asymmetric synthesis,
Trost and co-workers demonstrated the asymmetric total synthesis
of 1 via palladium-catalyzed regioselective and diastereoselective
cis-hydroxyamination of vinyl epoxide and isocyanate as the key
steps.15c Li et al. reported the asymmetric total synthesis of 1 using
anti-amino alcohol generated from diastereoselective reductive
coupling between alkyne and Garner’s aldehyde.13b
eoselective reduction of cyclic enone using
steps.
L-Selectride as the key
2. Results and discussion
The total synthesis of (þ)-valienamine (1) began with benzyl-
protected lactol 5 prepared from commercially available D-glucose
according to the reported literature (Scheme 1).17
Scheme 1.
As part of an ongoing research program aimed at the total
synthesis of biologically active polyhydroxylated alkaloids,16 we
Reduction of 5 and subsequent protection of primary alcohol
using TBDPSCl afforded compound in high yields. Swern
7

10386
Q.R. Li et al. / Tetrahedron 69 (2013) 10384e10390
Table 1
oxidation of 7 and subsequent Wittig reaction furnished olefin 7,
which was subjected under standard desilylation conditions to give
the corresponding product 9 in 92% yield. After oxidation of pri-
mary alcohol, treatment of aldehyde with vinylmagnesium bro-
mide in THF at 0 ꢁC provided an inseparable diastereomeric mixture
of allylic alcohol 10 with diastereoselectivity of 2.5:1 ratio by 1H
NMR analysis. Intramolecular olefin metathesis of diastereomeric
diene 10 with second generation Grubbs catalyst in refluxing
CH2Cl2 provided a separable diastereomeric mixture of 11a and 11b
in 60% and 25% yields, respectively.
Selected optimization for the diastereoselective amination of 13.a
Entry
Solvent
Time (h)
Yield (%)b
drc
1
2
3
4
5
CH2Cl2
n-Hexane
Et2O
CCl4
Toluene
12
24
30
14
15
55
10
31
45
61
6:1
15:1
6:1
8:1
10:1
a
Reaction conditions: (i) 13 (1 equiv), chlorosulfonyl isocyanate (3 equiv), Na2CO3
(4.5 equiv), solvent (0.25 M), 0 ꢁC. (ii) s-Na2SO3, room temperature, 12 h.
b
Isolated yield by flash column chromatography.
c
Diastereomeric ratio was determined by 1H NMR analysis of a crude reaction
To obtain an essential synthetic precursor 13 for the formation
of 14, we then sought selective reduction of enone 12 to alcohol
11b. Thus, allylic alcohols 11a and 11b were oxidized to give enone
12, which was subjected under reduction conditions using a bulky
mixture.
Based on the above results, we next focused on the synthesis of
(ꢀ)-1-epi-valienamine (2) from cyclic allylic alcohol 11a via a three-
step synthesis, as illustrated in Scheme 3.
hydride reagent, such as
Selectride attacked the ketone exclusively from the sterically ac-
cessible -face of enone 12 to give our desired product 11b in 80%
L-Selectride (Scheme 2). As expected, L-
b
After benzylation of 11a under standard reaction conditions,
cyclic 1,2-anti-polybenzyl ether 15 was treated with chlorosulfonyl
isocyanate under optimal reaction conditions (toluene, 0 ꢁC, 24 h)
to afford the corresponding 1,2-anti-amino alcohol 16 in high yield
(75%) with an excellent level of diastereoselectivity (dr¼27:1).
Benzyl and Cbz protection groups were removed using BCl3 to
provide (ꢀ)-1-epi-valienamine (2) with specific rotation and
spectral data (1H and 13C NMR) identical to those reported in the
literature.18
yield with an excellent level of diastereoselectivity. After benzyla-
tion of the primary alcohol, the diastereoselectivity of the reaction
3. Conclusion
We described a concise total synthesis of (þ)-valienamine and
(ꢀ)-1-epi-valienamine starting from readily available
D-glucose via
highly diastereoselective amination of cyclic benzylic ether with
retention of stereochemistry using chlorosulfonyl isocyanate,
intramolecular olefin metathesis, and diastereoselective reduction
of cyclic enone using L-Selectride as the key steps. It is believed that
this synthetic strategy can be applied to the preparation of a broad
range of biologically active compounds containing a chiral amine
moiety.
4. Experimental
4.1. General
Scheme 2.
Commercially available reagents were used without additional
purification, unless otherwise stated. All reactions were performed
under an inert atmosphere of nitrogen or argon. Nuclear magnetic
resonance spectra (1H and 13C NMR) were recorded on a Bruker
Unity 300 MHz and Varian Unit 500 MHz spectrometer for CDCl3
solutions, and chemical shifts are reported as parts per million
(ppm) relative to, respectively, residual CHCl3 dH (7.26 ppm) and
CDCl3 dC (77.0 ppm) as internal standards. Resonance patterns are
reported with the notations s (singlet), d (doublet), t (triplet), q
(quartet), and m (multiplet). In addition, the notation br is used to
indicate a broad signal. Coupling constants (J) are reported in hertz
(Hz). IR spectra were recorded on a Bruker Infrared spectropho-
tometer and are reported as cmꢀ1. Optical rotations were measured
with a Jasco P1020 polarimeter. Thin layer chromatography was
carried out using plates coated with Kieselgel 60F254 (Merck).
For flash column chromatography, E. Merck Kieselgel 60
(230e400 mesh) was used. LCemass spectra (LC/MS) were recor-
ded on a Waters 2767 LCMS system. High-resolution mass spectra
(HRMS) were recorded on a JEOL JMS-600 spectrometer.
of cyclic 1,2-syn-polybenzyl ether 13 using chlorosulfonyl iso-
cyanate was examined under various reaction conditions. Selected
results are summarized in Table 1. As shown in entry 1, the reaction
in methylene chloride at 0 ꢁC gave the desired product 14 with
a diastereomeric ratio of 6:1. Further study showed that n-hexane
solvent displayed the increased diastereoselectivity of 15:1, albeit
in significantly decreased yield (10%) (Table 1, entry 2). In addition,
other solvents, such as Et2O and CCl4 were less effective under the
present conditions (Table 1, entries 3 and 4). After further optimi-
zation, the best results were obtained by the use of toluene under
otherwise identical conditions, affording cyclic 1,2-syn-amino al-
cohol 14 in 61% yield with a high diastereoselectivity (10:1), as
shown in entry 5. Retention of stereochemistry can be explained by
SNi mechanism through a four-centered transition state.16g This
observation is consistent with the formation of a tight ion pair in
nonpolar n-hexane solvent, compared to relatively polar methylene
chloride solvent. Finally, debenzylation of 14 using BCl3 in the
presence of MeOH afforded (þ)-valienamine (1) in 72% yield. The
spectral data (1H NMR and 13C NMR) and specific rotation of 1 were
in full agreement with the reported values.12b
4.1.1. (2S,3R,4R,5R)-2,3,4,6-Tetrakis(benzyloxy)hexane-1,5-diol
(6). To a stirred solution of 5 (8.11 g, 0.015 mol) in anhydrous THF
(60 mL) was added LiAlH4 (1.404 g, 0.037 mol) at 0 ꢁC under N2. The

Q.R. Li et al. / Tetrahedron 69 (2013) 10384e10390
10387
Scheme 3.
mixture was stirred for 4 h at room temperature. The reaction
mixture was carefully quenched with H2O and then 1 M HCl
(10 mL) was added to make it clear. The aqueous layer was
extracted with EtOAc (35 mLꢂ2), and the organic layer was washed
with H2O and brine, dried over MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography (n-hexanes/
EtOAc¼2:1) to afford 7.98 g (14.7 mmol, 98% yield) of 6 as a yellow
organic layer was washed with H2O and brine, dried over MgSO4,
and concentrated in vacuo. Without purification the residue was
used in next step. To a stirred solution of methyl triphenylphos-
phonium bromide (18.2 g, 0.051 mol) in THF (85 mL) was slowly
added NaHMDS (51 mL, 0.051 mol) at 0 ꢁC under N2. The reaction
mixture was stirred for 2 h at room temperature to generate ylide. A
solution of ketone intermediate in THF (25 mL) was added to the
reaction mixture at 0 ꢁC. The reaction mixture was stirred for 1 h at
room temperature and quenched with H2O. The aqueous layer was
extracted with EtOAc (100 mLꢂ2) and the organic layer was washed
with H2O and brine, dried over MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography (n-hexanes/
EtOAc¼25:1) to afford 11.6 g (14.96 mmol, 88% yield) of 8 as a col-
syrup. Rf¼0.3 (n-hexanes/EtOAc¼2:1); ½a D28
þ3.4 (c 1.4, CHCl3); IR
ꢃ
(neat) n 3450, 3603, 2925, 1605, 1496, 1454, 1397, 1358, 1210, 1092,
736, 699, 605 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
2.05 (t, J¼6.0 Hz,
1H), 2.91 (d, J¼5.0 Hz, 1H), 3.54e3.64 (m, 3H), 3.65e3.81 (m, 3H),
3.87e3.89 (m, 1H), 4.01e4.05 (m, 1H), 4.51e4.72 (m, 8H), 7.21e7.36
(m, 20H); 13C NMR (125 MHz, CDCl3)
d 62.1, 70.9, 71.3, 73.3, 73.5,
73.7, 74.7, 76.9, 79.4, 79.7, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4,
128.6, 128.6, 128.7, 138.1, 138.2, 138.4; HRMS (FAB) calcd for
orless oil. Rf¼0.27 (n-hexanes/EtOAc¼15:1); ½a D28
þ63.3 (c 0.07,
ꢃ
CHCl3); IR (neat)
n 3060, 2929, 2856, 1738, 1588, 1428, 1260, 1111,
C
34H39O6 [MþH]þ 543.2747, found 543.2750.
823, 737, 700, 613, 506 cmꢀ1 1H NMR (500 MHz, CDCl3)
; d 1.01 (s,
9H), 3.62e3.67 (m, 2H), 3.78e3.81 (m, 1H), 3.90 (dd, J¼7.0, 3.5 Hz,
1H), 4.01 (s, 2H), 4.27e4.37 (m, 3H), 4.44e4.52 (m, 4H), 4.64 (d,
J¼11.0 Hz, 1H), 4.78 (d, J¼11.0 Hz, 1H), 5.19 (s, 1H), 5.41 (s, 1H),
7.18e7.42 (m, 26H), 7.59e7.62 (m, 4H); 13C NMR (125 MHz, CDCl3)
4.1.2. (3R,4R,5S)-1,3,4,5-Tetrakis(benzyloxy)-6-(tert-butyldiphenylsi-
lyloxy)hexan-2-ol (7). To a stirred solution of 6 (8.682 g, 0.016 mol)
in anhydrous CH2Cl2 (64 mL) was added tert-butyldiphenylsilyl-
chloride (4.948 g, 0.018 mol), triethylamine (2.67 mL, 0.019 mol)
and N,N-dimethylaminopyridine (0.078 g, 0.64 mmol) at room
temperature under N2. After stirring for 20 h, the reaction mixture
was carefully quenched with H2O. The aqueous layer was extracted
with CH2Cl2 (75 mLꢂ3). The combined organic layers were washed
with brine, dried over MgSO4, and concentrated in vacuo. The
residue was purified by flash column chromatography (n-hexanes/
EtOAc¼8:1) to afford 11.0 g (14.1 mmol, 88% yield) of 7 as a colorless
d
19.4, 27.1, 63.1, 69.9, 71.2, 72.8, 73.1, 75.4, 79.8, 80.3, 82.4, 116.1,
127.5, 127.6, 127.7, 127.8, 127.9, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6,
129.8,129.9,133.6,133.7,135.8,135.9,138.5,138.6,139.0,139.1,143.2;
HRMS (FAB) calcd for C51H57O5Si [MþH]þ 777.3975, found 777.3979.
4.1.4. (2S,3S,4R)-2,3,4-Tris(benzyloxy)-5-(benzyloxymethyl)hex-5-
en-1-ol (9). To a stirred solution of 8 (10.88 g, 0.014 mol) in THF
(56 mL) was added tetra-n-butylammonium fluoride (21 mL,
0.021 mol), stirred for 18 h at room temperature under N2. The
resulting mixture was quenched with H2O. The aqueous layer was
extracted with EtOAc (60 mLꢂ2) and the organic layer was washed
with H2O and brine, dried over MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography (n-hexanes/
EtOAc¼4:1) to afford 6.94 g (0.013 mol, 92% yield) of 9 as a yellow
oil. Rf¼0.27 (n-hexanes/EtOAc¼8:1); ½a D28
þ16.6 (c 3.0, CHCl3); IR
ꢃ
(neat)
n 3030, 2930, 2858, 1488, 1454, 1360, 1210, 1111, 824, 737,
700 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d 1.03 (s, 9H), 2.91 (d,
J¼5.0 Hz, 1H), 3.57 (d, J¼1.5 Hz, 1H), 3.59 (s, 1H), 3.80e3.97 (m, 6H),
4.45e4.54 (m, 5H), 4.61e4.64 (m, 3H), 7.09e7.42 (m, 26H),
7.42e7.64 (m, 4H); 13C NMR (125 MHz, CDCl3)
d 19.4, 27.1, 63.4, 71.2,
71.5, 73.3, 73.5, 73.6, 74.4, 76.8, 76.9, 77.4, 77.5, 77.7, 78.3, 79.9,127.7,
127.8, 127.9, 128.0, 128.1, 128.2, 128.4, 128.5, 128.6, 128.7, 128.8,
129.9, 130.1, 133.6, 133.7, 135.8, 138.3, 138.4, 138.5, 138.6; HRMS
(FAB) calcd for C50H57O6Si [MþH]þ 781.3924, found 781.3928.
oil. Rf¼0.45 (n-hexanes/EtOAc¼4:1); ½a D28
ꢃ
e23.5 (c 0.77, CHCl3); IR
(neat) n 3466, 3063, 2863, 1723, 1604, 1496, 1454, 1361, 1269, 1209,
1072, 916, 736, 698, 605 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 2.03 (br
s, 1H), 3.46e3.48 (m, 1H), 3.61e3.67 (m, 2H), 3.78 (dd, J¼11.0,
5.0 Hz, 1H), 3.98 (d, J¼12.5 Hz, 1H), 4.07 (d, J¼12.5 Hz, 1H), 4.28 (d,
J¼5.0 Hz, 1H), 4.33 (d, J¼11.5 Hz, 1H), 4.47e4.74 (m, 7H), 5.32 (d,
J¼1.0 Hz, 1H), 5.42 (d, J¼1.0 Hz, 1H), 7.24e7.34 (m, 20H); 13C NMR
4.1.3. tert-Butyldiphenyl ((2S,3S,4R)-2,3,4-tris(benzyloxy)-5-(benzy-
loxymethyl)hex-5-enyloxy)silane (8). To a stirred solution of oxalic
chloride (2.2 mL, 0.026 mol) in CH2Cl2 (60 mL) was carefully added
dimethylsulfoxide (3 mL, 0.041 mol) at ꢀ78 ꢁC and stirred for 1 h at
same temperature. The alcohol 7 (13.28 g, 0.017 mol) in CH2Cl2
(25 mL) and triethylamine (6.0 mL, 0.043 mol) was added to the
reaction mixture at ꢀ78 ꢁC. The reaction mixture was stirred for 2 h
at room temperature. The resulting mixture was quenched with H2O
and aqueous layer was extracted with CH2Cl2 (50 mLꢂ2). The
(125 MHz, CDCl3)
d 61.8, 70.6, 71.2, 72.8, 72.9, 73.5, 74.7, 75.1, 79.3,
80.8, 81.2, 116.9, 127.8, 127.7, 127.9, 128.0, 128.1, 128.2, 128.4, 128.5,
128.6, 128.7, 128.8, 138.2, 138.4, 138.5, 138.7, 142.7; HRMS (FAB)
calcd for C35H39O5 [MþH]þ 539.2797, found 539.2797.
4.1.5. (2R,3S,4R)-2,3,4-Tris(benzyloxy)-5-(benzyloxymethyl)hex-5-
enal (10). To a stirred solution of oxalic chloride (2.1 mL, 0.024 mol)

10388
Q.R. Li et al. / Tetrahedron 69 (2013) 10384e10390
in CH2Cl2 (70 mL) was carefully added dimethylsulfoxide (2.7 mL,
0.038 mol) at ꢀ78 ꢁC and stirred for 1 h at same temperature. The
alcohol 9 (8.62 g, 0.016 mol) and triethylamine (5.6 mL, 0.04 mol) in
CH2Cl2 (10 mL) was added to the reaction mixture at ꢀ78 ꢁC. The
reaction mixture was stirred for 2 h at room temperature. The
resulting mixture was quenched with H2O and the aqueous layer
was extracted with CH2Cl2 (100 mLꢂ2). The organic layer was
washed with H2O (20 mLꢂ2) and brine, dried over MgSO4, and
concentrated in vacuo. Without purification the residue was used
for next step. To a stirred mixture of the reaction intermediate in
THF (50 mL) was slowly added vinylmagnesium bromide (32 mL,
0.032 mol, 1.0 M in THF solution) at 0 ꢁC. After stirring for 1 h at
room temperature, the reaction mixture was quenched by aqueous
saturated NH4Cl (30 mL) and extracted with CH2Cl2 (60 mLꢂ2). The
organic layer was washed with H2O (30 mLꢂ2), dried over MgSO4,
and concentrated in vacuo. The residue was purified by column
chromatography (n-hexanes/EtOAc¼8:1) to afford 5.78 g (0.01 mol,
64% yield, dr¼2.5:1) of 10 as a colorless oil. Rf¼0.3 (n-hexanes/
temperature. The mixture was quenched with a solution of aqueous
saturated NaHCO3 (5 mL) and filtered with Celite pad. The aqueous
layer was extracted with CH2Cl2 (10 mLꢂ2). The organic layer was
washed with H2O (5 mLꢂ2), dried over MgSO4 and concentrated in
vacuo. The residue was purified by column chromatography (n-
hexane/EtOAc¼6:1) to afford 1.394 g (2.61 mmol, 64% yield) of 12 as
a colorless oil. Rf¼0.25 (n-hexane/EtOAc¼6:1); ½a D28
þ65.4 (c 1.2,
ꢃ
CHCl3); IR (neat)
n 3062, 3030, 2921, 2860, 1729, 1604, 1496, 1454,
1365, 1089, 1072, 736, 698 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 4.06
(d, J¼9.0 Hz, 2H), 4.10 (t, J¼1.5 Hz, 1H), 4.24 (s, 0.6H), 4.27 (d,
J¼1.0 Hz, 0.4H), 4.36 (t, J¼1.0 Hz, 0.5H), 4.37 (t, J¼1.0 Hz, 0.5H), 4.51
(d, J¼2.0 Hz, 2H), 4.68 (d, J¼11.0 Hz, 1H), 4.73 (d, J¼4.5 Hz, 1H), 4.76
(d, J¼4.0 Hz, 1H), 4.91 (d, J¼11.0 Hz, 1H), 5.00 (d, J¼11.0 Hz, 1H), 5.10
(d, J¼11.0 Hz, 1H), 6.21 (dd, J¼4.0, 2.0 Hz, 1H), 7.21e7.44 (m, 20H);
13C NMR (125 MHz, CDCl3)
d 69.2, 73.4, 74.6, 75.8, 75.9, 77.4, 79.4,
84.1, 85.1, 124.1, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6,
128.7, 128.8,137.6,137.9,138.1,138.3,159.2,196.9; HRMS (FAB) calcd
for C35H35O5 [MþH]þ 535.2484, found 535.2483.
EtOAc¼10:1); IR (neat)
n
3454, 3031, 1497, 1454, 1387, 1348 cmꢀ1
2.51 (d, J¼6.5 Hz, 0.7H), 3.21 (d,
;
1H NMR (500 MHz, CDCl3)
d
4.1.8. (1S,4R,5S,6S)-4,5,6-Tris(benzyloxy)-3-(benzyloxymethyl)cyclo-
J¼6.5 Hz, 0.3H), 3.55 (dd, J¼6.0, 4.5 Hz, 0.3H), 3.64 (dd, J¼6.0,
3.0 Hz, 0.7H), 3.81 (dd, J¼6.0, 4.5 Hz, 0.7H), 3.92 (m, 0.3H),
3.96e4.06 (m, 3H), 4.23e4.36 (m, 2.3H), 4.45e4.53 (m, 6.4H), 4.83
(d, J¼11.0 Hz, 0.3H), 5.07e5.45 (m, 4H), 5.71e5.78 (m, 1H),
hex-2-enol (11b). To a stirred solution of 12 (1.07 g, 0.002 mol) in
THF (50 mL) was added L
-Selectride (3 mL, 0.003 mol) at 0 ꢁC under
N2. The reaction mixture was stirred for 2 h at 0 ꢁC. The reaction
mixture was quenched with H2O and extracted with EtOAc
(50 mLꢂ2). The organic layer was washed with H2O and brine,
dried over MgSO4, and concentrated in vacuo. The residue was
purified by column chromatography (n-hexane/EtOAc¼4:1) to af-
ford 0.816 g (1.56 mmol, 76% yield) of 11b as a colorless oil.
7.23e7.36 (m, 20H); 13C NMR (125 MHz, CDCl3)
d 70.1, 70.7, 71.1,
71.9, 72.4, 72.5, 72.9, 73.1, 74.9, 75.4, 80.1, 80.2, 80.8, 81.1, 81.9, 82.7,
115.6, 116.1, 116.8, 117.8, 127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3,
128.4, 128.5, 128.6, 128.7, 128.8, 138.1, 138.4, 138.5, 138.7, 138.8,
142.7; HRMS (FAB) calcd for C37H41O5 [MþH]þ 565.2954, found
565.2955.
4.1.9. ((1S,2S,3S,4R)-5-(Benzyloxymethyl)cyclohex-5-ene-1,2,3,4-
tetrayl)tetrakis(oxy)tetrakis(methylene)tetrabenzene (13). To a stir-
red solution of 11b (0.63 g, 0.001 mol) in anhydrous THF (6.67 mL)
was added NaH (0.08 g, 0.002 mol, 60% in mineral oil) and BnBr
(0.17 mL, 0.002 mol) at 0 ꢁC under N2. The reaction mixture was
stirred for 12 h at room temperature. The reaction mixture was
carefully quenched with a cold aqueous solution of 10% NH4Cl
(10 mL). The aqueous layer was extracted with EtOAc (15 mLꢂ2).
The organic layer was washed with H2O and brine, dried over
MgSO4, and concentrated in vacuo. The residue was purified by
column chromatography (n-hexane/EtOAc¼8:1) to afford 0.501 g
(0.8 mmol, 80% yield) of 13 as a colorless oil. Rf¼0.28 (n-hexane/
4.1.6. (1R,4R,5S,6S)-4,5,6-Tris(benzyloxy)-3-(benzyloxymethyl)cyclo-
hex-2-enol (11a) and (1S,4R,5S,6S)-4,5,6-tris(benzyloxy)-3-(benzy-
loxymethyl)cyclohex-2-enol (11b). To a stirred solution of 10 (3.95 g,
0.007 mol) in CH2Cl2 (70 mL) was added Grubbs second generation
(0.594 g, 0.7 mmol) at room temperature. The reaction mixture was
stirred for 8 h at 50 ꢁC. The solution was evaporated to dryness and
the residue was purified by column chromatography (n-hexanes/
EtOAc¼6:1) to afford a separable mixture (3.19 g, 5.95 mmol, 85%
yield) of 11a and 11b as a colorless oil. 11a: Rf¼0.15 (n-hexane/
EtOAc¼4:1); mp 73e75 ꢁC; ½a D28
ꢃ
e65.8 (c 1.3, CHCl3); IR (neat)
;
n
3442, 3030, 1496, 1454, 1360 cmꢀ1
1H NMR (500 MHz, CDCl3)
EtOAc¼8:1); ½a 2D8
ꢃ
þ238.3 (c 0.04, CHCl3); IR (neat)
n 3030, 2921,
d
2.08 (d, J¼4.5 Hz, 1H), 3.56 (dd, J¼10.0,7.5 Hz, 1H), 3.84 (dd, J¼9.5,
2860, 1729, 1604, 1496, 1454, 1365, 1208, 1088, 908, 736, 698,
7.0 Hz, 1H), 3.90 (d, J¼12.0 Hz, 1H), 4.23 (d, J¼12.0 Hz, 1H),
4.28e4.32 (m, 2H), 4.45 (d, J¼12.0 Hz, 1H), 4.51 (d, J¼12.0 Hz, 1H),
4.68e4.73 (m, 2H), 4.78e4.82 (m, 2H), 4.90e4.97 (m, 2H), 5.73 (s,
605 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
3.58 (dd, J¼10.0, 3.5 Hz, 1H),
3.94 (d, J¼12.0 Hz, 1H), 4.07e4.09 (m, 1H), 4.17 (dd, J¼12.0, 7.0 Hz,
2H), 4.42 (d, J¼12.0 Hz, 1H), 4.62 (d, J¼12.0 Hz, 1H), 4.64e4.80 (m,
8H), 5.01 (d, J¼12.0 Hz, 1H), 5.89e5.90 (m, 1H), 7.04e7.46 (m, 25H);
1H), 7.24e7.35 (m, 20H); 13C NMR (125 MHz, CDCl3)
d 70.2, 71.5,
72.5, 74.7, 75.1, 75.3, 79.9, 83.7, 84.1, 127.4, 127.8, 127.9, 128.0, 128.1,
128.2, 128.3, 128.4, 128.5, 128.6, 128.7, 128.8, 136.2, 138.3, 138.5,
138.6,138.7; HRMS (CI) calcd for C35H35O5 [MꢀH]þ 535.2484, found
13C NMR (125 MHz, CDCl3)
d 70.5, 71.1, 71.9, 72.7, 72.8, 73.8, 75.1,
79.9, 80.1, 80.7, 123.7, 127.5, 127.6, 127.7, 127.8, 127.9, 128.0, 128.1,
128.2, 128.3, 128.5, 128.6, 128.7, 128.8, 129.9, 138.3, 138.8, 138.9,
139.0, 139.1, 140.3; HRMS (CI) calcd for C42H41O5 [MꢀH]þ 625.2954,
found 625.2954.
535.2478. 11b: Rf¼0.2 (n-hexane/EtOAc¼2:1); ½a D28
ꢃ
e40.3 (c 1.2,
CH2Cl2); IR (neat) n 3446, 3063, 2923, 1730, 1604, 1496, 1454, 1365,
1250, 1208, 1142, 1071, 910, 737, 698, 605 cmꢀ1; 1H NMR (500 MHz,
CDCl3)
d
2.56 (d, J¼3.5 Hz, 1H), 3.60 (dd, J¼9.5, 4.0 Hz, 1H), 3.94 (d,
4.1.10. Benzyl
(1S,4R,5S,6S)-4,5,6-tris(benzyloxy)-3-(benzyloxyme
J¼12.0 Hz, 1H), 4.06 (dd, J¼9.5, 7.0 Hz, 1H), 4.23 (m, 1H), 4.31 (t,
J¼4.0 Hz, 1H), 4.46 (d, J¼12.0 Hz, 2H), 4.64e4.80 (m, 6H), 4.87 (d,
J¼12.0 Hz, 1H), 5.91 (br s, 1H), 7.17e7.38 (m, 20H); 13C NMR
thyl)cyclohex-2-enylcarbamate (14). To a stirred solution of 13
(0.069 g, 0.11 mmol) in anhydrous toluene (0.74 mL) was added
Na2CO3 (0.132 g, 1.247 mmol) and chlorosulfonyl isocyanate
(0.07 mL, 0.831 mmol) at 0 ꢁC under N2. The reaction mixture was
stirred for 15 h at 0 ꢁC and quenched with H2O (1 mL). The aqueous
layer was extracted with EtOAc (2 mLꢂ2). The organic layer was
added to a solution of a solution of aqueous 25% Na2SO3 (2 mL), and
the reaction mixture was stirred for 24 h at room temperature.
The organic layer was washed with H2O and brine, dried over
MgSO4, and concentrated in vacuo. The residue was purified by
column chromatography (n-hexane/EtOAc¼6:1) to afford 0.049 g
(0.074 mmol, 61% yield) of 14 as a colorless oil. Rf¼0.23 (n-hexane/
(125 MHz, CDCl3)
d 31.1, 65.3, 70.5, 72.8, 73.1, 74.2, 74.9, 79.1, 79.2,
79.3, 124.8, 127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.5, 128.6,
128.7, 128.8, 138.2, 138.3, 138.7, 138.8, 139.9; HRMS (CI) calcd for
C
35H35O5 [MꢀH]þ 535.2484, found 535.2477.
4.1.7. (4R,5S,6R)-4,5,6-Tris(benzyloxy)-3-(benzyloxymethyl)cyclo-
hex-2-enone (12). To a stirred solution of 11 (1.667 g, 0.003 mol) in
CH2Cl2 (15 mL) was added DesseMartin periodinane (3.181 g,
7.5 mmol) at 0 ꢁC. The reaction mixture was stirred for 4 h at room

Q.R. Li et al. / Tetrahedron 69 (2013) 10384e10390
10389
EtOAc¼6:1); ½a 2D8
ꢃ
þ32.1 (c 1.69, CHCl3); IR (neat)
n
3322, 3031,
EtOAc¼4:1); mp 116e119 ꢁC; ½a D28
ꢃ
e15.5 (c 0.64, CHCl3); IR (neat) n
3323, 3031, 2924, 2855, 1720, 1605, 1498, 1454, 1361, 1204, 1068,
2862, 1719, 1498, 1454, 1296, 1238, 1069, 910, 738, 698, 605 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d
3.74 (br s, 1H), 3.81 (dd, J¼9.0, 4.5 Hz,
736, 698, 608 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
3.57 (t, J¼8.0 Hz,
1H), 3.90 (d, J¼12.0 Hz, 1H), 4.06 (br s, 1H), 4.24 (d, J¼12.0 Hz, 1H),
4.41 (d, J¼12.0 Hz, 1H), 4.48 (d, J¼12.0 Hz, 1H), 4.57e4.77 (m, 7H),
5.06 (d, J¼9.0 Hz, 1H), 5.12 (s, 2H), 5.82 (s, 1H), 7.17e7.38 (m, 25H);
1H), 3.89 (d, J¼4.0 Hz, 1H), 3.91 (d, J¼8.0 Hz, 1H), 4.24 (d, J¼8.0 Hz,
2H), 4.43e4.51 (m, 3H), 4.71e4.84 (m, 7H), 5.08e5.16 (m, 2H), 5.68
(s, 1H), 7.23e7.39 (m, 25H); 13C NMR (125 MHz, CDCl3)
d 52.3, 66.9,
13C NMR (125 MHz, CDCl3)
d
47.3, 67.0, 70.1, 72.2, 72.3, 73.9, 74.4,
70.5, 72.7, 74.3, 74.4, 74.7, 78.1, 79.9, 82.4, 126.2, 127.8, 127.9, 128.0,
128.1, 128.2, 128.3, 128.4, 128.5, 128.6, 128.7, 128.8, 136.5, 136.7,
138.3, 138.4, 138.5, 138.6, 156.1; HRMS (FAB) calcd for C43H44NO6
[MþH]þ 670.3169, found 670.3163.
76.1, 77.3, 77.5, 125.3, 127.6, 127.7, 127.9, 128.0, 128.1, 128.2, 128.3,
128.4, 128.5, 128.6, 128.7, 136.8, 137.3, 138.1, 138.4, 138.5, 156.3;
HRMS (FAB) calcd for
670.3170.
C
43H44NO6 [MþH]þ 670.3169, found
4.1.14. (1S,2S,3R,6R)-6-Amino-4-(hydroxymethyl)cyclohex-4-ene-
1,2,3-triol (2). To a stirred solution of 16 (262 mg, 0.39 mmol) in
anhydrous CH2Cl2 (8 mL) was added BCl3 (39 mL, 1.0 m in CH2Cl2
solution) at ꢀ78 ꢁC. The reaction mixture was stirred at for 24 h
ꢀ78 ꢁC. The reaction mixture was quenched with MeOH (10 mL)
and further stirred at ꢀ78 ꢁC for 1 h. The resulting mixture was
warmed to room temperature and concentrated in vacuo. The
residue was purified by ion-exchange resin DOWEX 50WX8-100
using 0.5 M NH4OH as eluent to afford 45.8 mg (0.26 mmol, 67%
4.1.11. (1S,2S,3R,6S)-6-Amino-4-(hydroxymethyl)cyclohex-4-ene-
1,2,3-triol (1). To a stirred solution of 14 (0.6 g, 0.89 mmol) in an-
hydrous CH2Cl2 (18 mL) was added BCl3 (80 mL, 1.0 M in CH2Cl2
solution) at ꢀ78 ꢁC. The reaction mixture was stirred for 24 h at
ꢀ78 ꢁC. The reaction mixture was quenched with MeOH (30 mL)
and further stirred at ꢀ78 ꢁC for 1 h. The resulting mixture was
warmed to room temperature and concentrated in vacuo. The
residue was purified by ion-exchange resin DOWEX 50WX8-100
using 0.5 M NH4OH as eluent to afford 109 mg (0.62 mmol, 70%
yield) of
2
as colorless syrup. Rf¼0.28 (CH2Cl2/CH3OH/
a 28
yield) of
1
as colorless syrup. Rf¼0.29 (CH2Cl2/CH3OH/
NH4OH¼3:1:0.1); ½ ꢃD þ26.7 (c 0.08, CH3OH); IR (neat)
n 3713,
NH4OH¼3:1:0.1); ½a D28
ꢃ
þ85.7 (c 0.04, CH3OH); IR (neat)
n
3727,
3333, 2923, 1737, 1609, 1512, 1375, 1102, 1054, 1033, 1014, 897, 822,
773, 621 cmꢀ1 1H NMR (500 MHz, D2O)
3.54e3.59 (m, 2H),
3.84e3.89 (m, 1H), 4.08e4.18 (m, 3H), 5.71e5.58 (m, 1H); 13C NMR
3333, 2923, 1737, 1611, 1516, 1372, 1244, 1093, 1053, 930, 722, 700,
;
d
618, 514 cmꢀ1 1H NMR (500 MHz, D2O)
; d 3.52e3.69 (m, 2H),
3.83e3.94 (m, 1H), 4.00e4.02 (m, 1H), 4.07e4.13 (m, 1H), 4.16 (s,
(125 MHz, CDCl3) d 53.8, 60.9, 71.6, 71.8, 116.9, 143.4; HRMS (CI)
1H), 5.70 (dd, J¼7.0, 3.5 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d
49.5,
calcd for C7H14NO4 [MþH]þ 176.0923, found 176.0924.
61.2, 66.8, 71.1, 71.8, 115.7, 146.1; HRMS (CI) calcd for C7H14NO4
[MþH]þ 176.0923, found 176.0923.
Acknowledgements
4.1.12. ((1R,2S,3S,4R)-5-(Benzyloxymethyl)cyclohex-5-ene-1,2,3,4-
tetrayl)tetrakis(oxy)tetrakis(methylene)tetrabenzene (15). To a stir-
red solution of 11a (0.45 g, 0.84 mmol) in anhydrous THF (4.2 mL)
was added NaH (0.05 g, 1.26 mmol, 60% in mineral oil) and BnBr
(0.1 mL, 1.26 mmol) at 0 ꢁC under N2. The reaction mixture was
stirred for 12 h at room temperature. The reaction mixture was
carefully quenched with a cold aqueous solution of 10% NH4Cl
(4 mL). The aqueous layer was extracted with EtOAc (10 mLꢂ2). The
organic layer was washed with H2O and brine, dried over MgSO4,
and concentrated in vacuo. The residue was purified by
column chromatography (n-hexane/EtOAc¼8:1) to afford 0.44 g
(0.71 mmol, 84% yield) of 15 as a colorless oil. Rf¼0.30 (n-hexane/
This work was supported by the National Research Foundation
of Korea (NRF-2011-002919 and NRF-2012-002506) funded by the
Ministry of Education, Science and Technology.
Supplementary data
Supplementary data available: 1H NMR and 13C NMR copies of
all compounds. Supplementary data related to this article can be
found at http://dx.doi.org/10.1016/j.tet.2013.09.098.
References and notes
EtOAc¼8:1); ½a 2D8
ꢃ
e234.4 (c 0.62, CHCl3); IR (neat)
n
3063, 3030,
1H
2859, 1605, 1497, 1454, 1359, 1069, 1027, 735, 697, 605 cmꢀ1
;
1. (a) Asano, N. Curr. Top. Med. Chem. 2003, 3, 471; (b) Elbein, A. D. FASEB J. 1991, 5,
3055; (c) Asano, N.; Nash, R. J.; Molyneux, R. J.; Fleet, G. W. J. Tetrahedron:
Asymmetry 2000, 11, 1645.
NMR (500 MHz, CDCl3)
d
3.77e3.83 (m, 2H), 3.94 (dd, J¼10.0,
6.0 Hz, 1H), 4.18e4.22 (m, 2H), 4.29 (d, J¼8.0 Hz, 1H), 4.31 (d,
J¼6.0 Hz, 1H), 4.43e4.53 (m, 2H), 4.65e4.94 (m, 6H), 4.98 (d,
J¼11.0 Hz, 1H), 5.78 (s, 1H), 7.18e7.39 (m, 25H); 13C NMR (125 MHz,
ꢀ
2. (a) Somsak, L.; Nagya, V.; Hadady, Z.; Docsa, T.; Gergely, P. Curr. Pharm. Des.
2003, 9, 1177; (b) Johnson, P. S.; Lebovitz, H. E.; Coniff, R. F.; Simonson, D. C.;
Raskin, P.; Munera, C. L. J. Clin. Endocrinol. Metab. 1998, 83, 1515.
€
3. (a) Greimel, P.; Spreitz, J.; Stutz, A. E.; Wrodnigg, T. M. Curr. Top. Med. Chem.
CDCl3) d 70.1, 72.4, 72.7, 75.2, 75.7, 75.8, 80.1, 83.9, 84.7, 125.4, 127.6,
2003, 3, 513; (b) Fleet, G. W. J.; Karpas, A.; Dwek, R. A.; Fellows, L. E.; Tyms, A. S.;
Peturrson, S.; Namgoong, S. K.; Ramsden, N. G.; Smith, P. W.; Son, J. C.; Wilson,
F.; Witty, D. R.; Jacob, G. S.; Rademacher, T. W. FEBS Lett. 1988, 237, 128.
4. Bitonti, A. J.; Sjoersma, A.; McCann, P. P. Eur. Patent Appl. EP423728, 1991.
5. (a) Nishimura, Y. Curr. Top. Med. Chem. 2003, 3, 575; (b) Ostrander, G. K.;
Scribner, N. K.; Rohrschneider, L. R. Cancer Res. 1988, 48, 1091; (c) Tsuruoka, T.;
Fukuyasu, H.; Ishii, M.; Usui, T.; Shibahara, S.; Inouye, S. J. Antibiot. 1996, 49, 155.
6. Kameda, Y.; Horii, S. J. Chem. Soc., Chem. Commun. 1972, 746.
7. (a) Kameda, Y.; Asano, N.; Teranishi, M.; Matsui, K. J. Antibiot. 1980, 33, 1573; (b)
Kameda, Y.; Asano, N.; Teranishi, M.; Yoshikawa, M.; Matsui, K. J. Antibiot. 1981,
34, 1237; (c) Asano, N.; Takeuchi, M.; Ninomiya, K.; Kameda, Y.; Matsui, K. J.
Antibiot. 1984, 37, 859.
127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6,
128.7, 128.8, 128.9, 136.6, 138.3, 138.5, 138.6, 138.8, 138.9; HRMS (EI)
calcd for C42H42O5 [M]þ626.3032, found 626.3031.
4.1.13. Benzyl (1R,4R,5S,6S)-4,5,6-tris(benzyloxy)-3-(benzyloxymet
hyl)cyclohex-2-enylcarbamate (16). To a stirred solution of 15
(0.07 g, 0.112 mmol) in anhydrous toluene (0.45 mL) was added
Na2CO3 (0.134 g, 1.26 mmol) and chlorosulfonyl isocyanate
(0.07 mL, 0.84 mmol) at 0 ꢁC under N2. The reaction mixture was
stirred for 12 h at 0 ꢁC and quenched with H2O (1 mL). The aqueous
layer was extracted with EtOAc (3 mLꢂ2). The organic layer was
added to a solution of a solution of aqueous 25% Na2SO3 (8 mL). The
reaction mixture was stirred for 24 h at room temperature. The
organic layer was washed with H2O and brine, dried over MgSO4,
and concentrated in vacuo. The residue was purified by column
8. (a) Ogawa, S.; Miyamoto, Y.; Nakajima, A. Chem. Lett. 1989, 725; (b) Ogawa, S.;
Nakajima, A.; Miyamoto, Y. J. Chem. Soc., Perkin Trans. 1 1991, 3287.
9. Mahmud, T. Nat. Prod. Rep. 2003, 20, 137.
€
10. Schmidt, D.; Frommer, W.; Junge, B.; Muller, K.; Wingender, W.; Trutsheit, E.
Naturwissenschaften 1977, 64, 536.
11. Paulsen, H.; Heiker, F. R. Angew. Chem., Int. Ed. Engl. 1980, 19, 904.
12. For selected examples on total synthesis of 1, see: (a) Fukase, H.; Horii, S. J. Org.
Chem. 1992, 57, 3651; (b) Kapferer, P.; Sarabia, F.; Vasella, A. Helv. Chim. Acta
1999, 82, 645; (c) Chang, Y.-K.; Lee, B.-Y.; Kim, D.-J.; Lee, G.-S.; Jeon, H.-B.; Kim,
K.-S. J. Org. Chem. 2005, 70, 3299; (d) Chang, Y.-K.; Lo, H.-J.; Yan, T.-H. Org. Lett.
2009, 11, 4278; (e) Lo, H.-J.; Chen, C.-Y.; Zheng, W.-L.; Yeh, S.-M.; Yan, T.-H. Eur. J.
chromatography (n-hexane/EtOAc¼4:1) to afford 0.056
g
(0.084 mmol, 75% yield) of 16 as a white solid. Rf¼0.29 (n-hexane/

10390
Q.R. Li et al. / Tetrahedron 69 (2013) 10384e10390
Org. Chem. 2012, 2780 For a selected example on formal synthesis of 1, see: (f)
Cumpstey, I. Tetrahedron Lett. 2005, 46, 6257.
13. (a) Krishna, P. R.; Reddy, P. S. Synlett 2009, 209; (b) Zhou, B.; Luo, Z.; Lin, S.; Li, Y.
Lett. 2007, 48, 6258; (e) Kim, I. S.; Li, Q. R.; Dong, G. R.; Woo, S. H.; Park, H.-j.;
Zee, O. P.; Jung, Y. H. Synlett 2008, 2985; (f) Kim, I. S.; Li, Q. R.; Dong, G. R.; Kim,
Y. C.; Hong, Y. J.; Lee, M.; Chi, K.-W.; Oh, J. S.; Jung, Y. H. Eur. J. Org. Chem. 2010,
1569; (g) Lee, S. H.; Kim, I. S.; Li, Q. R.; Dong, G. R.; Jeong, L. S.; Jung, Y. H. J. Org.
Chem. 2011, 76, 10011; (h) Dong, G. R.; Hong, S. M.; Kim, S. I.; Kim, I. S.; Jung, Y.
H. Eur. J. Org. Chem. 2012, 4200; (i) Kim, S. J.; Jeon, T. H.; Min, I. S.; Kim, I. S.;
Jung, Y. H. Tetrahedron Lett. 2012, 53, 3680; (j) Lee, S. H.; Park, S. J.; Kim, I. S.;
Jung, Y. H. Tetrahedron 2013, 69, 1877; (k) Min, I. S.; Kim, S. I.; Hong, S.; Kim, I. S.;
Jung, Y. H. Tetrahedron 2013, 69, 3901.
Synlett 2012, 913.
14. (a) Shing, T. K. M.; Li, T.-Y.; Kok, S. H. L. J. Org. Chem. 1999, 64, 1941; (b) Kok, S. H.
L.; Lee, C.-C.; Shing, T. K. M. J. Org. Chem. 2001, 66, 7184.
15. (a) Ogawa, S.; Shibata, Y.; Nose, T.; Suami, T. Bull. Chem. Soc. Jpn. 1985, 58, 3387;
(b) Knapp, S.; Naughton, A. B. J.; Dhar, T. G. M. Tetrahedron Lett. 1992, 33, 1025;
(c) Trost, B. M.; Chupak, L. S.; Lubbers, T. J. Am. Chem. Soc. 1998, 120, 1732.
16. For a review, see: (a) Kim, I. S.; Jung, Y. H. Heterocycles 2011, 83, 2489 For recent
examples, see: (b) Kim, I. S.; Li, Q. R.; Lee, J. K.; Lee, S. H.; Lim, J. K.; Zee, O. P.;
Jung, Y. H. Synlett 2007, 1711; (c) Kim, I. S.; Lee, H. Y.; Jung, Y. H. Heterocycles
2007, 71, 1787; (d) Kim, I. S.; Ryu, C. B.; Li, Q. R.; Zee, O. P.; Jung, Y. H. Tetrahedron
17. Dasari, B.; Jogula, S.; Borhade, R.; Balasubramanian, S.; Chandrasekar, G.; Ki-
tambi, S. S.; Arya, P. Org. Lett. 2013, 15, 432.
18. Cumpstey, I.; Gehrke, S.; Erfan, S.; Cribiu, R. Carbohydr. Res. 2008, 343, 1675.