FULL PAPER

DOI: 10.1002/cjoc.201600050

Several Enantiopure Chiral Building Blocks Derived from

D-Mannose and a Formal Synthesis of Dubiusamine C
Dongxing Tan,a,b Murong Xu,b Zejun Xu,b Yikang Wu,*,b and Jun You*,a
a

Key Laboratory of Green Chemical Technology of College of Heilongjiang Province, School of Chemical and
Environmental Engineering, Harbin University of Science and Technology, Harbin, Heilongjiang 150040, China
b
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
Several multi-functional chiral building blocks derived from D-mannose are developed, which may find diverse
utilities as sources of 1-hydroxy-3-methyl structural units in enantioselective synthesis of many natural products. A
formal synthesis of natural dubiusamine-C is also presented.
Keywords carbohydrates, condensation, natural products, stereochemistry, alcohols

Introduction
Installation of stereogenic centers of predefined absolute configurations is an issue of central importance in
the synthesis of optically active compounds. One of the
broadly employed approaches to accomplish such tasks
is to use so-called chiral building blocks, which allowed
for introduction of the stereogenic centers of desired
absolute configurations at the same time when assembling the target structures.
Chiral building blocks are normally derived from
chiral pool compounds, the readily available and inexpensive species of high optical purity. Carbohydrates
such as D-glucose, D-xylose and D-mannose are among
those often chosen chiral pool compounds, which after
removal of the undesired redundant stereogenic centers
and proper functional group transformation allowed for
access to a range of useful chiral building blocks.[1]
Recently, we reported the synthesis of furospongin-1
and dihydrofurospongin-2 using D-mannose as the
source of the stereogenic carbon centers.[2] As an extension of that work, we next made substantial efforts to
elaborate a key intermediate therein into various readyfor-use chiral building blocks of reasonable shelf life.
These multifunctional group-containing small molecules
all carry a 1-hydroxy-3-methyl structural motif with the
absolute configurations clearly defined and therefore
may find diverse utilities in synthesis of natural products with similar structural units, such as those[3] (17)
shown in Figure 1. The details are given below.

OH

O
OH

O
O

H
N

O
H
O

O
O

O
O

OH
O
HO

O
5

4
OH

O
OH

O
6

HO

O
7

Figure 1 Examples for natural products containing 1-hydroxy3-methyl units: furospongin-1 (1), 7,8-epoxufurospongin-1 (2),
dubiusamine-C (3), murrayacoumarin C (4), epoxudine A (5), a
simple -lactone (6) and amphidinolide B (7).

Results and Discussion

The present work began with reduction of lactone 8,
a D-mannose derived chiral building block developed in
our previous work,[2] to gain access to several other
building blocks suitable for different syntheses.

* E-mail: yikangwu@sioc.ac.cn
Received January 20, 2016; accepted February 18, 2016; published online March 23, 2016.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201600050 or from the author.
Chin. J. Chem. 2016, 34, 669677

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As shown in Scheme 1, treatment of lactone 8 with

LiAlH4 gave diol 9. Subsequent exposure of 9 to
I2/Ph3P/imidazole[4a-4c] led to corresponding iodide 10,
which might allow for incorporation of this structural
unit into various target structures by alkylation. However, because of the rather close spatial relationship
between the OH and the iodide, this iodide was not very
stable. Protection of the OH group hence appeared necessary.

LiAlH4, THF

OH
9

TBSOTf
2,6-lutidine

11

OH

Me2C(OMe)2
p-TsOH, 75%

13

I
PivO

OH
12

Attempt to protect the OH in 10 with TBS

(t-butyldimethylsilyl) under the frequently employed
conditions (TBSCl/imidazole/DMF/r.t.) was not successful, affording a mixture of idodide 10 and the corresponding chloride. However, use of more reactive
TBSOTf (t-butyldimethylsilyltriflate) led to substantial
improved reaction rate. Under such conditions, pure 11
could be obtained in 41% yield along with 59% of recovered 10.
An alternative to make use of the unstable 10 is to
convert it into 13. Thus, hydrolysis of the acetonide protecting group in 10 with 60% aq. AcOH[5] provided an
intermediate triol. Regioselective protection of the primary hydroxyl group of the triol under the conventional
t-BuCOCl/base (Et3N or pyridine) conditions led to a
complex mixture, presumably due to intramolecular
etherification of the hydroxyl groups. Fortunately, the
desired protection could be realized satisfactorily using
t-BuCO2H/DCC.[6] The resulting 12 was then masked
with Me2C(OMe)2 to give 13.
Direct hydrolytic removal of the acetonide protecting group in 6 with 60% AcOH delivered diol 14
(Scheme 2). Treatment of 14 with I2/Ph3P/imidazole[4d,4e]
at refluxing temperature led to the known[7] 15, a bifunctional species that may combine with other molecules through either the vinyl or the carbonyl group.
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O
H

17

(1) aq. AcOH

Ph3PCH3Br

(2) n-Bu2SnO
p-TsCl, Et3N

THF, n-BuLi

61%
O

(1) 60% AcOH, 8 h 77%

(2) DCC, CH2Cl2, t-BuCO2H overall

OPiv

OH
O

18

OH
10

HO

15

16

O
O

CH2Cl2
-20 oC to r.t.
41%

TBSO

81%
100%

Ph3P, DIAD
CHCl3

HO

THF I2, Ph3P

63% imidazole

(1) NaIO4
silica gel 41%
over
(2) NaBH4 2 steps

OH

80%

THF, reflux
82%

OH
14

DIBAL-H

I2, Ph3P
imidazole

H
HO

81%

670

O
60% aq. AcOH

Scheme 1

Scheme 2

19

(3) K2CO3, MeOH

79% over
3 steps

H
O

OH
20

Oxidative cleavage of the vicinal diol with NaIO4silica gel[8] followed by NaBH4 reduction afforded the
known[9] alcohol 16. Alternatively, exposure of diol 14
to I2/Ph3P/imidazole in refluxing[10] THF led to alkene
15. Under the Ph3P/DIAD (diisopropyl azodicarboxylate)[11] conditions, 14 afforded epoxide 17 in 81%.
Modification of the lactone carbonyl group in 6 also
allowed for several potentially useful building blocks.
Thus, partial reduction with DIBAL-H provided lactol
18, which could be readily elaborated into alkene 19 by
reaction with the Wittig reagent formed in situ from
Ph3PCH3Br/n-BuLi. The newly formed vinyl group may
serve as the reaction site for chain elongation, with or
without protection of the hydroxyl group.
Hydrolysis of the acetonide protecting group in 19
resulted in an intermediate triol, which could be readily
transformed into the corresponding epoxide 20 through
selective tosylation of the primary OH under the
n-Bu2SnO/p-TsCl/Et3N[12] conditions followed by exposure to K2CO3/MeOH.
Lactone 8 could also be converted[13] into corresponding Weinreb amides 2123 as shown in Scheme
3. Reaction of 8 with Me(MeO)NHHCl in the presence
of AlMe3[13a] opened the lactone ring to give an amide.
The newly freed hydroxyl group was masked as a benzyl ether. The acetonide was then hydrolyzed to release
a vicinal diol unit, which on oxidative cleavage followed by NaBH4 reduction and TES protection gave the
desired amide 23.
A synthetic application of 15 was then explored, as
shown in Scheme 4. Through cross metathesis with
3-butenol in the presence of the commercially available
Grubbs II catalyst, alcohol 24 was obtained in 79%
yield.[7,14] Although conventional hydrogenation of 24

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Enantiopure Chiral Building Blocks Derived from D-Mannose and Synthesis of Dubiusamine C

sis (Scheme 5). Unfortunately, the reaction gave exclusively the cyclization product 32; no 27 could be detected at all.

Scheme 3
MeO
(1)

O
O

NH . HCl
Me
AlMe3, THF

(2) NaH, BnBr, DMF

70% over 2 steps

OBn
21

Me

(1) 60% aq. AcOH, 24 h 77%

(2) NaIO4, THF-H2O over
(3) NaBH4, MeOH 3 steps
TESO

O
N
OBn
23

Me TESCl, Et N, DMAP
3

OH

O Grubbs II, CH2Cl2

OBn

15

29

91%

N
H

Bn

Me

OMe

22

p-TsO

TsO(CH2)2C=CH2

O
N

CH2Cl2, 100%

OMe

Scheme 5

OMe

30
(traces)

BnNH2
O

K2CO3
MeCN
reflux

Scheme 4
H
O

Grubbs II, CH2Cl2

HO
H

3-buten-1-ol
79%

H
15

O
Grubbs II

15

24
CH2Cl2

OH
O

NsNH2 r.t.
DIAD 12 h
Ph3P 84%

p-TsNHNH2, air

H
25

NaHCO3, 100%

O
H

89%
O
N

27

Ns

p-TsNHNH2

reflux, 80%

28

H
N

O
H

O
H

NaHCO3, air
MeO(CH2)2OH

NHNs
26

O2N

Ns
PhSH (ref. 3c)
K2CO3 95%
O

Ns =

O
S
O

over Pd/C to saturate the C-C double bond was not successful (leading to only 33% of 25 along with
ring-opening side products), reduction with diimide[15,16]
(generated in situ from p-TsNHNH2) afforded 25, an
intermediate in Togos[3c] synthesis of ()-dubiusamine
C, as expected.
Alternatively, 24 could also be converted to 26 under
the Mitsunobu conditions, which could further combine
with another molecule of 24 in the presence of Ph3P/
DIAD at elevated temperature to give 27 in 89% yield.
The C-C double bonds were then reduced using diimide,
providing 28, the immediate precursor to natural dubiusamine-C in Togos synthesis.
We also tried cross metathesis reaction between 15
and 29 in hope to improve the efficiency of the syntheChin. J. Chem. 2016, 34, 669677

N
31
CBz

90%

N
(no 27 at all)
CBz
32

Conclusions

24, Ph3P
DIAD, 60 oC

Several useful chiral building blocks with two

pre-installed stereogenic centers taken from inexpensive
D-mannose were developed. All these bi-/multi-functional small molecules contain 1-hydroxy-3-methyl
structural motif and may be conveniently used in synthesis to introduce 1-hydroxy-3-methyl partial structure(s). A formal synthesis of natural dubiusamine-C
was also achieved. These enantiopure chiral building
blocks, if made commercially available, may allow for
quick starts of many syntheses.

Experimental
The NMR spectra were recorded on either an Agilent 500/54 NMR spectrometer (operating at 500 MHz
for 1H) or an Agilent 400/54 instrument (operating at
400 MHz for 1H). IR spectra were measured on a Nicolet 380 Infrared spectrophotometer. ESI-MS data
were acquired on a Shimadzu LCMS-2010EV mass
spectrometer. ESI-HRMS data were obtained with a
Thermo Fisher Scientific LTQ FT Ultra spectrometer.
Optical rotations were measured on a Jasco P-1030 polarimeter. Melting points were uncorrected (measured
on a hot stage melting point apparatus equipped with a
microscope). Toluene and CH2Cl2 were dried with activated 4 MS (molecular sieves). All chemicals were
reagent grade and used as purchased. Column chromatography was performed on silica gel (300400 mesh)
under slightly positive pressure. Petroleum ether (chromatography eluent) refers to the fraction boiling between 60 and 90 .

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LiAlH4 (83 mg, 2.18 mmol) was added slowly to a

solution of 8 (218 mg, 1.09 mmol) in dry THF (20 mL)
stirred in an ice-water bath. The mixture was then
stirred at ambient temperature for 1.5 h (TLC showed
completion of the reaction). Water (5 mL) was added,
followed by 10% NaOH (5 mL) and more water (15
mL). The mixture was stirred for 30 min before being
filtered through Celite and gave diol 9 as a colorless oil
(233 mg, 1.14 mmol, crude yield: 100%), which was
pure enough to be used directly in the next step: []D25
0.95 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3) :
4.02 (dd, J7.2, 5.7 Hz, 1H), 4.003.84 (m, 4H), 3.72
(ddd, J10.4, 5.2, 1.7 Hz, 1H), 3.57 (dd, J10.7, 4.6
Hz, 1 H), 3.35 (dd, J10.6, 8.0 Hz, 1H), 1.891.80 (m,
1H), 1.53 (ddd, J14.3, 6.2, 1.8 Hz, 1 H), 1.42 (s, 3H),
1.381.32 (m, 1H), 1.36 (s, 3H), 0.92 (d, J6.9 Hz,
3H); 13C NMR (125 MHz, CDCl3) : 109.0, 79.0, 70.4,
68.3, 65.5, 38.3, 33.9, 26.4, 25.2, 17.5; IR (film) v: 3377,
2988, 2985, 2933, 2875, 1457, 1372, 853, 794 cm1;

ESI-MS m/z: 227.9 ([MNa] ). ESI-HRMS calcd for

C10H20NaO4 ([MNa] ): 227.1254, found 227.1248.

L, 0.22 mmol) in dry CH2Cl2 (2 mL) stirred in an

ice-water bath. The mixture was then stirred at ambient
for 48 h. Water (1 mL) was added. The mixture was
extracted with EtOAc (10 mL3). The combined organic layers were washed with water and brine, and
dried over anhydrous Na2SO4. Removal of the drying
agent by filtration and rotary evaporation gave a crude
oil, which was purified by column chromatography
(151 petroleum ether/EtOAc) on silica gel to afford
11 as a colorless oil (20 mg, 0.047 mmol, 49%) along
with recovered 10 (17 mg, 0.054 mmol, 47%). Data for
11: []D236.13 (c 1.0, CHCl3). 1H NMR (500 MHz,
CDCl3) : 4.013.92 (m, 2H), 3.823.75 (m, 2H),
3.25 (dd, J4.5, 9.6 Hz, 1H), 3.20 (dd, J5.8, 9.6 Hz,
1H), 1.761.69 (m, 1H), 1.56 (ddd, J5.3, 7.3, 12.8
Hz, 1H), 1.40 (s, 3 H), 1.38 (ddd, J4.7, 8.2, 12.8 Hz,
1H), 1.33 (s, 3H), 1.00 (d, J6.5 Hz, 3H), 0.88 (s, 9H),
0.1 (s, 3H), 0.09 (s, 3H); 13C NMR (125 MHz, CDCl3) :
109.1, 79.1, 70.7, 66.5, 42.1, 30.6, 26.6, 25.9, 25.7, 25.4,
20.9, 18.4, 18.1, 3.9, 4.1; IR (film) v: 2959, 2931,
2886, 2858, 1462, 1370, 733, 686 cm1; ESI-MS m/z:

451.4 ([MNa] ). ESI-HRMS calcd for C16H34IO3Si

([MH] ): 429.1316, found 429.1324.

(1S,3R)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-4iodo-3-methylbutan-1-ol (10)

(2R,3S,5S)-1-Pivaloyloxy-5-methyl-6-iodo-hexan-2,3diol (12)

To a solution of diol 9 (233 mg, 1.14 mmol) in THF

(7 mL) stirred at ambient temperature were added in
turn Ph3P (330 mg, 1.26 mmol), imidazole (160 mg,
2.28 mmol) and I2 (350 mg, 1.37 mmol). Stirring was
continued for 2 h (with the flask wrapped with aluminum foil to avoid any direct light irradiation). When
TLC showed completion of the reaction, 10% aq.
Na2S2O3 (3 mL) was added to decompose the excess I2.
The mixture was extracted with CH2Cl2 (30 mL3).
The combined organic layers were washed with water
and brine, and dried over anhydrous Na2SO4. Removal
of the drying agent by filtration and rotary evaporation
gave a crude oil, which was purified by column chromatography (11 petroleum ether/EtOAc) on silica gel
to afford iodide 10 as a colorless oil (213 mg, 0.68
mmol, 60%). []D245.4 (c 1.0, CHCl3). 1H NMR (400
MHz, CDCl3) : 4.033.96 (m, 2H), 3.943.89 (m,
1H), 3.85 (dt, J5.6, 2.7 Hz, 1H), 3.29 (dd, J5.0, 9.7
Hz, 1H), 3.25 (dd, J5.7, 9.7 Hz, 1H), 2.03 (br s, 1H,
OH), 1.841.77 (m, 1H), 1.43 (s, 3H), 1.421.38 (m,
1H), 1.37 (s, 3 H), 1.30 (ddd, J2.6, 9.2, 11.8 Hz, 1H),
1.02 (d, J6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) :
109.1, 78.9, 68.6, 64.4, 39.3, 31.4, 26.5, 25.2, 20.0, 18.4;
IR (film) v: 3459, 2984, 2959, 2930, 1456, 1372, 855

cm1; ESI-MS m/z: 337.1 ([M Na] ). ESI-HRMS

calcd for C10H19INaO3 ([MNa] ): 337.0271, found

337.0262.

A solution of 10 (58 mg, 0.18 mL) was dissolved in

aq. AcOH (60% w/v, 1.5 mL). The mixture was stirred
at ambient temperature for 10 h (TLC showed completion of the reaction). Toluene (2 mL) was added. The
mixture was evaporated on a rotary evaporator to dryness. The colorless oily residue (crude triol, 51 mg, 0.18
mmol, 100%) was dissolved in CH2Cl2 (1 mL). To this
solution were added pyvalic acid (5 mg, 0.051 mmol),
DCC (14 mg, 0.069 mmol) and DMAP (2 mg, 0.016
mmol). The mixture was stirred at ambient temperature
for 12 h (TLC showed completion of the reaction). Direct chromatography of the mixture on silica gel (21
petroleum ether/EtOAc) gave diol 12 as a white solid
(12 mg, 0.033 mmol, 75% from 10), from which the
following data were collected: m.p. 6970 . []D23
21.2 (c 0.7, CHCl3); 1H NMR (500 MHz, CDCl3) :
4.29 (dd, J6.2, 11.8 Hz, 1H), 4.23 (dd, J3.4, 11.8
Hz, 1H), 3.763.68 (m, 2 H), 3.29 (dd, J5.1, 9.7 Hz,
1H), 3.26 (dd, J6.0, 10.1 Hz, 1H), 1.851.76 (m,
1H), 1.60 (ddd, J4.2, 10.4, 14.2 Hz, 1H), 1.40 (ddd,
J2.4, 9.4, 11.8 Hz, 1H), 1.23 (s, 9H), 1.02 (d, J6.5
Hz, 3H); 13C NMR (125 MHz, CDCl3) : 179.4, 73.5,
70.2, 65.4, 39.0, 38.9, 31.5, 27.2, 20.0, 18.4; IR (film) v:
3452, 2961, 2932, 2873, 1711, 1480, 1460, 1398, 990,

938 cm1; ESI-MS m/z: 381.1 ([MNa] ). ESI-HRMS

calcd for C12H24O4I ([M H] ): 359.0714, found

359.0713.

tert-Butyl((1S,3S)-1-((R)-2,2-dimethyl-1,3-dioxolan4-yl)-4-iodo-3-methylbutoxy)dimethylsilane (11)

((4R,5S)-5-((S)-3-Iodo-2-methylpropyl)-2,2-dimethyl1,3-dioxolan-4-yl)methyl pivalate (13)

TBSOTf (28 L, 0.12 mmol) was added to a solution

of alcohol 10 (36 mg, 0.11 mmol) and 2,6-lutidine (25

A mixture of 12 (12 mg, 0.033 mmol) and p-TsOH

(monohydrate, 1 mg, 0.0033 mmol) in Me2C(OMe)2 (1

(1S,3R)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-3methylbutan-1,4-diol (9)

672

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Chin. J. Chem. 2016, 34, 669677

Enantiopure Chiral Building Blocks Derived from D-Mannose and Synthesis of Dubiusamine C

mL) was stirred at ambient temperature for 3 h (TLC

showed completion of the reaction). Et3N (0.5 mL) was
added. The mixture was concentrated on a rotary evaporator to dryness. The residue was purified by column
chromatography (15 1 petroleum ether/EtOAc) on
silica gel to give 13 as a white solid (10 mg, 0.025
mmol, 77% from 12). Data for 13: m.p. 3941 .
[]D192.5 (c 0.5, CHCl3). 1H NMR (500 MHz, CDCl3)
: 4.264.21 (m, 2H), 4.124.06 (m, 2H), 3.30 (dd,
J4.8, 9.7 Hz, 1H), 3.23 (dd, J5.6, 9.7 Hz, 1H),
1.781.72 (m, 1H), 1.66 (ddd, J4.3, 10.6, 13.9 Hz,
1H), 1.45 (s, 3H), 1.35 (s, 3H), 1.31 (ddd, J2.9, 4.5,
12.0 Hz, 1H), 1.22 (s, 9H), 1.04 (d, J6.5 Hz, 3H); 13C
NMR (125 MHz, CDCl3) : 178.1, 108.5, 75.2, 74.8,
62.6, 38.8, 35.9, 31.8, 28.2, 27.2, 25.6, 19.9, 18.3; IR
(film) v: 2961, 2933, 2873, 1732, 1480, 1459, 1380, 892,

867 cm1; ESI-MS m/z: 421.2 ([MNa] ). ESI-HRMS

calcd for C15H28O4I ([M H] ): 399.1027, found

399.1025.
(3S,5S)-5-((R)-1,2-Dihydroxyethyl)-3-methyldihydrofuran-2(3H)-one (14)
A solution of 8 (181 mg, 0.91 mL) was dissolved in
aq. AcOH (60% w/v, 2.5 mL). The mixture was stirred
at ambient temperature for 24 h (TLC showed completion of the reaction). Toluene (3 mL) was added. The
mixture was evaporated on a rotary evaporator to dryness to give 14 as a white solid (117 mg, 0.73 mmol,
81%). m.p. 3738 . []D24 5.8 (c 1.0, CHCl3). 1H
NMR (500 MHz, CDCl3) : 4.42 (dt, J10.4, 5.3 Hz,
1H), 3.91 (br q, J5.6 Hz, 1H), 3.82 (br s, 2H, OH),
3.72 (dd, J3.7, 11.6 Hz, 1H), 3.61 (dd, J6.6, 11.5
Hz, 1H), 2.762.68 (m, 1H), 2.44 (ddd, J6.0, 8.9,
12.7 Hz, 1H), 1.89 (br dq, J1.8, 12.1 Hz, 1H), 1.27 (d,
J7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) : 180.2,
78.1, 72.1, 62.8, 35.3, 31.6, 14.9; IR (film) v: 3412,
2977, 2938, 2883, 1755, 1647, 1457, 1380, 930, 900

cm1; ESI-MS m/z: 183.0 ([M Na] ). ESI-HRMS

calcd for C7H12NaO4 ([MNa] ): 183.0628, found

183.0624.
(3S,5S)-3-Methyl-5-vinyldihydrofuran-2(3H)-one
(15)
To a solution of diol 14 (31 mg, 0.2 mmol) in THF
(2 mL) stirred at ambient temperature were added in
turn Ph3P (157 mg, 0.6 mmol), imidazole (82 mg, 1.2
mmol) and I2 (152 mg, 0.6 mmol). The mixture was
then refluxed under argon (balloon) for 3 h (TLC
showed completion of the reaction). To the mixture (already cooled to ambient temperature) was added aq.
NaS2O3 (10% v/v) until the color of I2 faded. The mixture was extracted with EtOAc (10 mL3). The combined organic layers were washed with water and brine,
and dried over anhydrous Na2SO4. Removal of the drying agent by filtration and rotary evaporation gave a
crude oil, which was purified by column chromatography (101 petroleum ether/EtOAc) on silica gel to afford the known[7] alkene 15 as a colorless oil (20 mg,
Chin. J. Chem. 2016, 34, 669677

0.16 mmol, 82% from 14). []D2211.0 (c 1.0, CHCl3)

(lit.[7] []D0.8 (CH2Cl2)). 1H NMR (400 MHz, CDCl3)
: 5.88 (ddd, J6.6, 10.5, 17.1 Hz, 1H), 5.39 (dt, J
17.2, 1.1 Hz, 1H), 5.27 (dt, J10.5, 1.0 Hz, 1H), 4.81
4.75 (m, 1H), 2.762.65 (m, 1H), 2.57 (ddd, J12.5,
8.4, 6.7 Hz, 1H), 1.67 (br dq, J1.7, 12.1 Hz, 1H), 1.29
(d, J7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) :
179.2, 135.7, 118.0, 78.7, 37.5, 35.8, 15.1; IR (film) v:
2953, 2930, 2857, 1782, 1718, 1462 cm1.
(3S,5S)-5-(Hydroxymethyl)-3-methyldihydrofuran2(3H)-one (16)
A solution of 14 (90 mg, 0.56 mmol) in CH2Cl2 (3
mL) was added to a mixture of NaIO4/silica gel[8] (2.88
g) in CH2Cl2 (3 mL) stirred at ambient temperature. The
mixture was stirred at the same temperature for 2 h
(TLC showed completion of the reaction). Solids were
filtered off. The filtrate was concentrated on a rotary
evaporator to dryness to give an oil (the crude intermediate aldehyde, 40 mg, 0.31 mmol), which was directly
dissolved in MeOH (1 mL). NaBH4 (14 mg, 0.37 mmol)
was added. The mixture was stirred at ambient temperature for 2 h. Water (0.2 mL) was then added. The
mixture was extracted with CH2Cl2 (15 mL3). The
combined organic layers were washed with brine and
dried over anhydrous Na2SO4. Removal of the drying
agent by filtration and the solvent by rotary evaporation
gave alcohol 16 (30 mg, 0.23 mmol, 41% from 14),
which was rather pure as shown by 1H NMR. []D24
12.1 (c 0.88, EtOH) (lit.[17] []D2417.2 (c 0.9, EtOH)).
1
H NMR (500 MHz, CDCl3) : 4.504.46 (m, 1H),
3.88 (dd, J2.5, 12.6 Hz, 1H), 3.61 (dd, J4.9, 12.6
Hz, 1H), 2.762.67 (m, 1H), 2.37 (ddd, J6.1, 9.0,
12.6 Hz, 1H), 1.77 (br dq, J1.7, 11.9 Hz, 1H), 1.27 (d,
J7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) : 179.6,
78.7, 63.5, 35.6, 31.6, 15.1 (both the 1H and 13C NMR
were fully consistent with those in the literature[18]).
(3S,5S)-3-Methyl-5-((R)-oxiran-2-yl)dihydrofuran2(3H)-one (17)
A solution of diol 14 (118 mg, 0.74 mmol), Ph3P
(291 mg, 1.11 mmol) and DIAD (220 L, 1.11 mmol)
in CHCl3 (7 mL) was stirred at refluxing temperature
for 36 h (TLC showed completion of the reaction). Solvent was removed by rotary evaporation. The residue
was purified by column chromatography (31 petroleum ether/EtOAc) on silica gel to give 17 as a colorless
oil (85 mg, 0.60 mmol, 81%). []D25 2.8 (c 1.0, CHCl3).
1
H NMR (500 MHz, CDCl3) : 4.40 (ddd, J3.9, 6.1,
10.1 Hz, 1H), 3.24 (dt, J4.0, 2.7 Hz, 1H), 2.88 (t, J
4.6 Hz, 1H), 2.752.68 (m, 1H), 2.66 (dd, J2.6, 4.7
Hz, 1H), 2.42 (ddd, J6.1, 8.8, 12.5 Hz, 1H), 1.72 (br
dq, J2.1, 12.2 Hz, 1H), 1.30 (d, J7.1 Hz, 3H); 13C
NMR (125 MHz, CDCl3) : 178.6, 77.0, 51.3, 44.2, 34.9,
31.4, 15.1; IR (film) v: 2979, 2937, 2880, 1774, 1456,
1403, 1379, 897, 853 cm1; ESI-MS m/z: 143.1 ([M

H] ). ESI-HRMS calcd for C7H10NaO3 ([MNa] ):

165.0522, found 165.0520.

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(1S,3S)-1-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-3methylpent-4-en-1-ol (19)
DIBAL-H (1.0 mol/L, in cyclohexane, 0.94 mL, 0.94
mmol) was added to a solution of 8 (144 mg, 0.72 mmol)
in dry CH2Cl2 (2 mL) stirred at 72 under argon
(balloon). After completion of the addition, the mixture
was stirred at the same temperature for 1 h (TLC
showed completion of the reduction). MeOH (1 mL)
was added, followed by aq. saturated potassium sodium
tartrate. The mixture was stirred at ambient temperature
for 3 h. Solids were removed by filtration with suction
through Celite. The filtrate was concentrated on a rotary
evaporator to give the crude 18 as a colorless oil (154
mg, 0.76 mmol, 100%), which was directly dissolved in
THF (5 mL).
To a solution of Ph3PMeBr (2.27 g, 6.34 mmol) in
dry THF (5 mL) stirred in an ice-water bath under argon
(balloon) was added n-BuLi (2.0 mol/L, in hexanes, 3.0
mL, 6.0 mmol). The orange mixture was stirred at ambient temperature for 4 h. The above mentioned solution
of crude hemiacetal was then added. The mixture was
then stirred at ambient temperature for 12 h. Aq. saturated NH4Cl was added to quench the excess Wittig reagent. The resulting colorless mixture was extracted
with EtOAc (30 mL3). The combined organic phases
were washed with water and brine, and dried over anhydrous Na2SO4. Removal of the solvent by rotary
evaporation and purification by column chromatography
(41 petroleum ether/EtOAc) afforded 19 as a colorless oil (100 mg, 0.50 mmol, 63% overall from 8).
[]D26 13.2 (c 0.9, CHCl3). 1H NMR (400 MHz,
CDCl3) : 5.80 (ddd, J7.6, 10.3, 17.5 Hz, 1H), 5.05
(dt, J17.2, 1.5 Hz, 1H), 4.97 (dq, J10.3, 0.9 Hz,
1H), 4.033.96 (m, 2H), 3.953.90 (m, 1H), 3.89
3.84 (m, 1H), 2.442.34 (m, 1H), 2.06 (br s, 1H, OH),
1.461.40 (m, 2H), 1.43 (s, 3H), 1.37 (s, 3H), 1.04 (d,
J6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) : 144.7,
113.0, 109.0, 78.7, 69.2, 64.7, 39.4, 34.8, 26.5, 25.3,
19.7; IR (film) v: 3455, 3079, 2986, 2932, 1640, 1657,

1372, 913, 855 cm1. ESI-MS m/z: 223.1 ([MNa] ).

ESI-HRMS calcd for C11H20NaO3 ([M Na] ):

223.1305; found 223.1302.
(1S,3S)-3-Methyl-1-((R)-oxiran-2-yl)pent-4-en-1-ol
(20)
A solution of 19 (60 mg, 0.3 mmol) in aq. AcOH
(60%, 1 mL) was stirred at ambient temperature for 12 h
(TLC showed completion of the hydrolysis). Toluene (1
mL) was added. The mixture was concentrated on a rotary evaporator to dryness and further evacuated under
oil pump vacuum to give a residue (crude triol, 54 mg,
0.34 mmol). A portion of the crude triol (20 mg, 0.125
mmol) was dissolved in THF (1 mL), to which were
added n-Bu2SnO (4 mg, 0.013 mmol), Et3N (30 L,
0.22 mmol) and p-TsCl (24 mg, 0.125 mmol). The mixture was stirred at ambient temperature for 2 h. Another
portion of Et3N (15 L, 0.11 mmol) and p-TsCl (12 mg,
0.063 mmol) were added. Stirring was continued for
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another 2 h when TLC showed completion of the reaction. The mixture was diluted with Et2O. Solids were
filtered off. The filtrate was concentrated on a rotary
evaporator to afford the intermediate tosylate (32 mg,
0.103 mmol, 82% from 19), which was dissolved in
MeOH (2 mL) and stirred with K2CO3 (27 mg, 0.2
mmol) in an ice-water bath for 3 h (TLC showed completion of the reaction). The mixture was diluted with
EtOAc. Solids were filtered off. The filtrate was concentrated on a rotary evaporator to furnish epoxide 20 as
a colorless oil (14 mg, 0.098 mmol, 96% from the intermediate tosylate, 79% overall from 19). []D23 27.9
(c 0.73, CHCl3). 1H NMR (500 MHz, CDCl3) : 5.80
(ddd, J7.6, 10.3, 17.5 Hz, 1H), 5.05 (dt, J17.2, 1.3
Hz, 1H), 4.97 (dq, J10.3, 0.9 Hz, 1H), 3.913.88 (m,
1H), 3.033.01 (m, 1H), 2.81 (dd, J2.8, 5.1 Hz, 1H),
2.74 (dd, J4.1, 5.0 Hz, 1H), 2.462.41 (m, 1H), 1.83
(br s, 1H, OH), 1.62 (ddd, J6.9, 8.5, 13.9 Hz, 1H),
1.51 (ddd, J4.4, 7.5, 13.8 Hz, 1H), 1.06 (d, J6.7 Hz,
3 H); 13C NMR (125 MHz, CDCl3) : 144.6, 113.1, 67.0,
54.7, 43.7, 40.4, 34.5, 20.0; IR (film) v: 2958, 2923,
2855, 1260, 801, 690 cm1. ESI-MS m/z: 143.1 ([M

H] ). EI-HRMS calcd for C8H14O2 (M ): 142.1000,

found 142.0994.
(2S,4S)-4-(Benzyloxy)-4-((R)-2,2-dimethyl-1,3dioxolan-4-yl)-N-methoxy-N,2-dimethylbutanamide
(21)
AlMe3 (1.0 mol/L, in heptane, 1.4 mL, 1.4 mmol)
was slowly added to a mixture of Me(MeO)NHHCl
(134 mg, 1.37 mmol) and dry THF (2 mL) stirred in an
ice-water bath under argon (balloon) to give a clear solution, stirring was continued for another 45 min. A solution of 8 (77 mg, 0.39 mmol) in dry THF (2 mL) was
added dropwise. The mixture was then stirred in the
ice-water bath for 4 h (TLC showed completion of the
reaction). Aq. saturated potassium sodium tartrate (3
mL) was added. The mixture was stirred at ambient
temperature for 4 h (giving a two-phase clear solution).
The phases were separated. The aqueous layer was extracted with EtOAc (10 mL3). The combined organic
layers were washed with brine and dried over anhydrous
Na2SO4. Removal of the solvent left an oil (96 mg, 0.37
mmol, 96%), which was dissolved in DMF (2 mL) and
stirred with NaH (80% w/w in mineral oil, 33 mg, 1.11
mmol) in an ice-water bath for 30 min. BnBr (0.14 mL,
1.18 mmol) was introduced. Stirring was then continued
at ambient temperature for 4 h. Water (2 mL) was added
to quench the excess hydride. The mixture was extracted with EtOAc (10 mL3). The combined organic
layers were washed with brine and dried over anhydrous
Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography (21 petroleum ether/
EtOAc) on silica gel gave 21 as a colorless oil (110 mg,
0.28 mmol, 73% overall from 8). []D22 13.5 (c 2.1,
CHCl3). 1H NMR (500 MHz, CDCl3) : 7.357.25 (m,
5H), 4.76 (d, J11.6 Hz, 1H), 4.61 (d, J11.6 Hz, 1H),
4.134.10 (m, 1H), 4.03 (dd, J6.6, 8.0 Hz, 1H), 3.88

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Enantiopure Chiral Building Blocks Derived from D-Mannose and Synthesis of Dubiusamine C

(t, J7.7 Hz, 1H), 3.653.63 (m, 1H), 3.62 (br s, 3H),
3.12 (br s, 3H), 3.113.10 (m, 1H), 1.88 (ddd, J6.0,
8.4, 14.3 Hz, 1H), 1.56 (ddd, J4.3, 8.0, 12.3 Hz, 1H),
1.41 (s, 3H), 1.35 (s, 3H), 1.07 (d, J6.9 Hz, 3H); 13C
NMR (100 MHz, CDCl3) : 177.6, 138.6, 128.2, 127.8,
127.5, 109.0, 78.8, 76.4, 72.7, 65.8, 61.3, 35.5, 32.1,
31.4, 26.3, 25.3, 16.9. IR (film) v: 3064, 3030, 2984,
2936, 2881, 1661, 1497, 1416, 1381, 857, 739, 699 cm1;

ESI-MS m/z: 374.3 ([MNa] ). ESI-HRMS calcd for

C19H29NNaO5 ([MNa] ): 374.1938, found 374.1934.

(2S,4S)-4-(Benzyloxy)-5-hydroxy-N-methoxy-N,2dimethylpentanamide (22)
A solution of 21 (50 mg, 0.13 mmol) in aq. AcOH
(60%, 1.5 mL) was stirred at ambient temperature for 12
h (TLC showed completion of the hydrolysis). Toluene
(2 mL) was added. The mixture was concentrated on a
rotary evaporator to dryness and further evacuated under oil pump vacuum to give a residue (crude diol, 39
mg, 0.125 mmol), which was directly dissolved in
THF-H2O (11 v/v, 2 mL). NaIO4 (41 mg, 0.19 mmol)
was added. The mixture was stirred in an ice-water bath
for 30 min (TLC showed completion of the reaction)
and extracted with EtOAc (10 mL3). The combined
organic layers were washed with water and brine and
dried over anhydrous Na2SO4. Removal of the solvent
by rotary evaporation gave a residue, which was directly
dissolved in MeOH (1 mL) and stirred in an ice-water
bath. NaBH4 (8 mg, 0.19 mmol) was then added. Stirring was continued at the same temperature for 4 h before water (0.5 mL) was added. The mixture was extracted with EtOAc (10 mL3). The combined organic
layers were washed with water and brine and dried over
anhydrous Na2SO4. Removal of the solvent by rotary
evaporation and chromatography (1 1 petroleum
ether/EtOAc) on silica gel afforded the intermediate
alcohol 22 as a colorless oil (21 mg, 0.19 mmol, 77%
over 3 steps from 21). []D2332.5 (c 1.0, CHCl3). 1H
NMR (500 MHz, CDCl3) : 7.367.26 (m, 5H), 4.61 (d,
J11.7 Hz, 1H), 4.56 (d, J11.7 Hz, 1H), 3.66 (br s,
3H), 3.633.52 (m, 3H), 3.16 (br s, 3H), 3.06 (br s, 1H,
OH), 2.262.24 (m, 1H), 2.17 (ddd, J5.3, 8.8, 14.2
Hz, 1H), 1.57 (dt, J14.2, 5.5 Hz, 1H), 1.12 (d, J6.9
Hz, 3H); 13C NMR (100 MHz, CDCl3): : 177.8, 138.5,
128.4, 127.7, 127.7, 77.4, 71.2, 63.7, 61.4, 33.9, 32.3,
31.0, 18.1; IR (film) v: 3431, 3030, 2934, 2872, 1655,
1496, 1455, 1388, 740, 699 cm1; ESI-MS m/z: 304.2

([MNa] ). ESI-HRMS calcd for C15H24O4N ([M

H] ): 282.1700, found 282.1698.

(2S,4S)-4-(Benzyloxy)-5-triethylsilyloxy-N-methoxyN,2-dimethylpentanamide (23)
TESCl (13 L, 0.08 mmol) was added to a solution
of alcohol 22 (21 mg, 0.07 mmol), Et3N (14 L, 0.098
mmol) and DMAP (1 mg, 0.005 mmol) in dry CH2Cl2
(1 mL) stirred in an ice-water bath. The mixture was
then stirred at ambient for 30 min. Aq. saturated NH4Cl
(1 mL) was added. The mixture was concentrated on a
Chin. J. Chem. 2016, 34, 669677

rotary evaporator. The residue was purified by column

chromatography (11 petroleum ether/EtOAc) on silica gel to give 23 as a colorless oil (30 mg, 0.08 mmol,
100%). []D26 10.5 (c 1.0, CHCl3). 1H NMR (500 MHz,
CDCl3) : 7.367.24 (m, 5H), 4.76 (d, J11.8 Hz, 1H),
4.56 (d, J11.8 Hz, 1H), 3.72 (dd, J5.9, 10.5 Hz,
1H), 3.62 (br s, 3H), 3.60 (dd, J4.9, 10.7 Hz, 1H),
3.543.47 (m, 1H), 3.12 (br s, 3H), 3.133.04 (m,
1H), 1.85 (ddd, J5.8, 8.9, 14.3 Hz, 1H), 1.59 (ddd,
J4.0, 8.1, 12.1 Hz, 1H), 1.05 (d, J6.9 Hz, 3H), 0.96
(t, J8.0 Hz, 9H), 0.61 (q, J7.9 Hz, 6H); 13C NMR
(125 MHz, CDCl3) : 139.3, 128.2, 127.8, 127.4, 78.1,
72.1, 66.1, 61.4, 35.9, 32.6, 31.7, 17.1, 6.8, 4.6; IR (film)
v: 3030, 2955, 2912, 2876, 1665, 1498, 1456, 1385, 805,

742 cm1; ESI-MS m/z: 418.3 ([MNa] ). ESI-HRMS

calcd for C21H38O4NSi ([MH] ): 396.2565, found

396.2563.
(3S,5S)-5-((E)-4-Hydroxybut-1-en-1-yl)-3-methyldihydrofuran-2(3H)-one (24)
A solution of 3-butenol (79 mg, 1.1 mmol) and 15
(90 mg, 0.71 mmol) in dry CH2Cl2 (4 mL) was added to
a sealed flask equipped with a reflux condenser containing Grubbs II catalyst (31 mg, 0.036 mmol) stirred
under argon (balloon). The stirring was continued at
refluxing temperature under argon for 2.5 h (TLC
showed completion of the reaction). The mixture was
separated on silica gel (eluting with EtOAc) to give 24
as a colorless oil (containing traces of the cis isomer, 95
mg, 0.56 mmol, 79% from 15). []D2414.1 (c 2.0,
CHCl3). 1H NMR (400 MHz, CDCl3) : 5.86 (dt, J
15.4, 6.9 Hz, 1H), 5.59 (dd, J7.3, 15.5 Hz, 1H),
4.814.75 (m, 1H), 3.68 (t, J6.5 Hz, 2 H), 2.76
2.65 (m, 2H), 2.55 (ddd, J5.7, 8.4, 12.6 Hz, 1H), 2.34
(q, J6.4 Hz, 2 H), 1.67 (dt, J1.8, 12.2 Hz, 1H), 1.27
(d, J7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) :
179.5 (179.7), 132.0 (131.7), 129.7 (129.5), 78.7 (74.0),
61.2 (61.3), 37.5 (37.7), 35.7, 35.2, (31.0), 14.8 (14.7),
with the corresponding signals for the cis isomer in
parentheses; IR (film) v: 3418, 2973, 2935, 2878, 1767,
1674, 1455, 1377, 971, 928 cm1; ESI-MS m/z: 193.1

([MNa] ). ESI-HRMS calcd for C9H15O3 ([MH] ):

171.1016, found 171.1015.
(3S,5R)-5-(4-Hydroxybutyl)-3-methyldihydrofuran2(3H)-one (25)
A solution of 24 (13 mg, 0.067 mmol), p-TsNHNH2
(114 mg, 0.61 mmol) and NaHCO3 (51 mg, 0.61 mmol)
in EtO(CH2)2OH (2 mL) was refluxed (in a 135
bath) under air (balloon) for 1 h. TLC showed completion of the reaction. The mixture was separated (eluting
with EtOAc) on silica gel and gave 25 as a white solid
(13 mg, 0.075 mmol, 98%): m.p. 6263 (lit.[3c]
m.p. 65.566 ). []D2522.6 (c 1.0, CHCl3) (lit.[3c]
[]D23 20.0 (c 1.0, CHCl3)); 1H NMR (500 MHz,
CDCl3) : 4.35 (ddt, J10.5, 7.4, 5.3 Hz, 1H), 3.66 (t,
J6.2 Hz, 2H), 2.722.63 (m, 1H), 2.50 (ddd, J5.4,
8.6, 12.6 Hz, 1H), 1.811.73 (m, 1H), 1.691.44 (m,

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6H), 1.27 (d, J7.1 Hz, 3H); 13C NMR (125 MHz,
CDCl3) : 179.6, 78.5, 62.5, 37.3, 35.9, 35.2, 32.3, 21.6,
15.1; IR (film) v: 3320, 2973, 2947, 2904, 2871, 1751,
1469, 1363, 952, 929 cm1.
4-(((E)-4-((2S,4S)-4-Methyl-5-oxotetrahydrofuran-2yl)but-3-en-1-yl)amino)-3-nitrobenzenesulfonic acid
(26)
DIAD (32 L, 0.16 mmol) was added dropwise to a
solution of 24 (20 mg, 0.12 mmol), NsNH2 (61 mg, 0.3
mmol), and Ph3P (42 mg, 0.16 mmol) in 1 1
THF-toluene (v/v, 2 mL) stirred in an ice-water bath
under argon (balloon). After completion of the addition,
the mixture was stirred at ambient temperature for 12 h.
The solvent was removed on a rotary evaporator. The
residue was purified by column chromatography (15
petroleum ether/EtOAc) on silica gel to give 26 as a
colorless oil (35 mg, 0.099 mmol, 84%). []D24 0.5 (c
1.0, CHCl3). 1H NMR (400 MHz, CDCl3) : 8.158.13
(m, 1H), 7.907.87 (m, 1H), 7.797.74 (m, 2H), 5.70
(dt, J15.5, 6.8 Hz, 1H), 5.52 (dd, J6.7, 15.5 Hz,
1H), 5.40 (t, J5.9 Hz, 1 H), 4.744.68 (m, 1H),
3.253.14 (m, 2H), 2.732.62 (m, 1H), 2.54 (ddd, J
5.7, 8.4, 12.6 Hz, 1H), 2.33 (q, J6.7 Hz, 2H), 1.67
1.58 (m, 1H), 1.27 (d, J7.0 Hz, 3H); 13C NMR (100
MHz, CDCl3) : 179.1, 148.0, 133.7, 133.5, 132.9,
131.3, 130.9, 130.0, 125.5, 78.0, 42.7, 37.6, 35.7, 32.1,
14.9. IR (film) v: 3329, 3095, 2975, 2935, 2875, 1766,
1675, 1592, 1541, 1440, 1365, 741, 729 cm1; ESI-MS

m/z: 377.0 ([M Na] ). ESI-HRMS calcd for

C15H19O6N2S ([MH] ): 355.0958, found 355.0958.

N,N-Bis((3E)-4-((2S,4S)-4-methyl-5-oxooxolan-2yl)but-3-en-1-yl)-2-nitrobenzene-1-sulfonamide (27)
DIAD (16 L, 0.081 mmol) was added dropwise to a
solution of 26 (22 mg, 0.062 mmol), 24 (16 mg, 0.093
mmol), and Ph3P (21 mg, 0.081 mmol) in toluene (1 mL)
stirred in an ice-water bath under argon (balloon). After
completion of the addition, the mixture was stirred at
60 for 3 h. The solvent was removed on a rotary
evaporator. The residue was purified by column chromatography (15 petroleum ether/EtOAc) on silica gel
to give 26 as a colorless oil (28 mg, 0.056 mmol, 89%
from 26). []D26 0.8 (c 1.0, CHCl3). 1H NMR (400
MHz, CDCl3) : 8.037.99 (m, 1H), 7.757.69 (m,
2H), 7.687.63 (m, 1H), 5.70 (dt, J15.4, 6.8 Hz, 2H),
5.55 (dd, J6.9, 15.5 Hz, 2H), 4.69 (dt, J10.6, 6.2
Hz, 2H), 3.453.32 (m, 4H), 2.722.62 (m, 2H), 2.52
(ddd, J5.7, 8.4, 13.9 Hz, 2H), 2.34 (q, J7.0 Hz, 4H),
1.671.58 (m, 2H), 1.27 (d, J7.0 Hz, 6H); 13C NMR
(100 MHz, CDCl3) : 179.2, 147.9, 133.8, 133.4, 131.8,
130.8, 130.7, 130.6, 124.3, 78.3, 46.6, 37.7, 35.8, 31.0,
15.0; IR (film) v: 3095, 2975, 2935, 2878, 1769, 1675,
1544, 1455, 1373, 1344, 778, 733 cm1; ESI-MS m/z:

529.2 ([MNa] ). ESI-HRMS calcd for C24H31O8N2S

([MH] ): 507.1796, found 507.1794.

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N,N-Bis((3E)-4-((2S,4S)-4-methyl-5-oxooxolane-2yl)butyl)-2-nitrobenzene-1-sulfonamide (28)
A solution of 27 (20 mg, 0.039 mmol), p-TsNHNH2
(82 mg, 0.44 mmol) and NaHCO3 (37 mg, 0.44 mmol)
in EtO(CH2)2OH (2 mL) was refluxed (in a 135
bath) under air (balloon) for 1.5 h. TLC showed completion of the reaction. The mixture was separated
(eluting with 15 petroleum ether/EtOAc) on silica gel
and gave 28 as a colorless oil (16 mg, 0.031 mmol,
80%). []D2720.3 (c 1.0, CHCl3) (lit.[3c] []D19 22.5
(c 0.9, CHCl3)); 1H NMR (400 MHz, CDCl3) : 8.01
7.99 (m, 1H), 7.717.69 (m, 2H), 7.637.61 (m, 1H),
4.30 (ddt, J10.5, 7.3, 5.4 Hz, 2H), 3.413.17 (m,
4H), 2.712.61 (m, 2H), 2.48 (ddd, J5.4, 8.5, 13.0
Hz, 2H), 1.721.34 (m, 14H), 1.26 (d, J7.0 Hz, 3H);
13
C NMR (100 MHz, CDCl3) : 179.5, 148.0, 133.5,
133.4, 131.7, 130.7, 124.2, 78.3, 47.2, 37.3, 35.9, 34.9,
27.9, 22.5, 15.1.
4-(((2S,4S)-4-Methyl-5-oxooxolan-2-yl)butyl)but-3en-1-yl 4-methylbenzene-1-sulfonate (29)
A solution of p-TsO(CH2)2CHCH2 (82 mg, 0.36
mmol) and 15 (30 mg, 0.24 mmol) in dry CH2Cl2 (4 mL)
was added to a sealed flask equipped with a reflux condenser containing Grubbs II catalyst (10 mg, 0.012
mmol) stirred under argon (balloon). The stirring was
continued at refluxing temperature under argon for 12 h
(TLC showed completion of the reaction). The mixture
was separated on silica gel (eluting with 31 petroleum
ether/EtOAc) to give 29 as a colorless oil (70 mg, 0.22
mmol, 91% from 15). []D278.6 (c 2.0, CHCl3). 1H
NMR (500 MHz, CDCl3) : 7.76 (d, J8.3 Hz, 2H),
7.34 (d, J8.0 Hz, 2H), 5.715.65 (m, 1H), 5.55
5.50 (m, 1H), 4.704.65 (m, 1H), 4.04 (t, J6.5 Hz,
2H), 2.692.61 (m, 1H), 2.49 (ddd, J5.7, 8.4, 12.6
Hz, 1H), 2.43 (s, 3H), 2.432.39 (m, 2H), 1.57 (br dq,
J1.7, 12.2 Hz, 1H), 1.25 (d, J7.1 Hz, 3H); 13C
NMR (125 MHz, CDCl3) : 179.0, 144.9, 132.8, 131.1,
129.8, 128.9, 127.8, 78.0, 68.9, 37.6, 35.7, 31.5, 21.6,
15.0; IR (film) v: 2970, 2932, 1770, 1676, 1598, 1494,

1358, 816, 773 cm1. ESI-MS m/z: 347.3 ([MNa] ).

ESI-HRMS calcd for C16H20NaO5S ([M Na] ):

347.0924, found 347.0926.

Acknowledgement
This work was supported by the National Natural
Science Foundation of China (Nos. 21532002,
21372248) and the Chinese Academy of Sciences.

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