Highly selective approach for the total synthesis of (+)-heliconol A

Article abstract of DOI:10.1016/j.tetasy.2008.05.031

The total synthesis of heliconol A, a representative of a new class of polyketide-derived hemiketals containing a reduced furanocyclopentane unit, has been achieved via the stereoselective reduction of a ketone, the face selective dihydroxylation, a Sonogashira coupling reaction, and a cis-selective reduction as the key steps.

Full text of DOI:10.1016/j.tetasy.2008.05.031

Tetrahedron: Asymmetry 19 (2008) 1568–1571
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Tetrahedron: Asymmetry
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Highly selective approach for the total synthesis of (+)-heliconol A
*
Debendra K. Mohapatra , Bhaskar Chatterjee, Mukund K. Gurjar
Organic Chemistry Division, National Chemical Laboratory, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The total synthesis of heliconol A, a representative of a new class of polyketide-derived hemiketals con-
taining a reduced furanocyclopentane unit, has been achieved via the stereoselective reduction of a
ketone, the face selective dihydroxylation, a Sonogashira coupling reaction, and a cis-selective reduction
as the key steps.
Received 24 April 2008
Accepted 29 May 2008
Available online 14 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
HO
OH
OH
OH
In 2006, Gloer et al. reported the isolation, structure elucidation,
and biological activity of three new compounds, heliconol A–C 1–3
(Fig. 1), all containing a reduced furanocyclopentane unit from the
fresh water aquatic fungus Helicodendron giganteum Glen-Bott
(Helotiaceae) collected from a sample of submerged wood in Alas-
ka.1 Heliconols A–C 1–3 were tested against Candida albicans (ATCC
14053), Staphylococcus aureus (ATCC 29213), Bacillus subtilis (ATCC
6051), Escherichia coli (ATCC 25922),2 Aspergillus flarus (NRRL
6541), and Fusarium verticillioides (NRRL 25457). Heliconol A 1
was found to inhibit the growth of F. verticilloides and exhibit pro-
found activity against C. albicans, S. aureus, and B. subtilis.3 The rel-
ative and absolute stereochemistry of heliconol A 1 was prima facie
established by NOESY and single-crystal X-ray crystallographic
analysis of its dibromobenzoate derivative.
O
1
OTBDPS
OTBS
OTBDPS
OH
( )
6
( )
7
O
2
3
OH
O
OTBDPS
( )
6
HO
OH
OH
OH
5
4
R
Scheme 1. Retrosynthetic analysis of (+)-heliconol A.
O
Heliconol A -C
via a stereoselective reduction using the Corey–Bakshi–Shibata
reagent.
1. R = Me
2. R = CH2OH
3. R = CO2H
2. Results and discussion
Figure 1. Heliconol A–C.
The synthesis began with the commercially available cyclo-
pentenone 5, which was converted to its 2-iodo-2-cyclopentenone
6 derivative following a literature method.5 Compound 6 was
reduced, from the desired enantioface (here, b), with BH3ꢁTHF
A total synthesis of enantiomeric (ꢀ)-heliconol A was recently
reported by She et al.4 Our retrosynthetic analysis reveals that
the furan ring could be obtained by highly selective dihydroxyla-
tion (Scheme 1). The cis-double bond should be accessible by
alkyne reduction. The alkyne functionality could be introduced
utilizing a Sonogashira coupling reaction and a hydroxyl group
and
a
catalytic amount of (R)-2-methyl-CBS-oxazaborolidine6
leading to the allylic alcohol 7 on a 4 g scale in 85% yield (92%
ee) (Scheme 2). Further enhancement of the enantiomeric purity
>96% (HPLC analysis) was achieved by recrystallization.
The spectroscopic and analytical data {½a D25
¼ ꢀ25:5 (c 1.0,
ꢂ
* Corresponding author. Tel.: +91 20 25902586; fax: +91 20 25902629.
E-mail address: dk.mohapatra@ncl.res.in (D.K. Mohapatra).
CHCl3); lit.7
½
a 2D5
ꢂ
¼ ꢀ28:3 (c 1.0, CHCl3)} were in good agreement
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.05.031

D. K. Mohapatra et al. / Tetrahedron: Asymmetry 19 (2008) 1568–1571
1569
with those reported in the literature, which confirmed the absolute
stereochemistry of alcohol 7.7 The acetylenic side chain was then
introduced by (Ph3P)2PdCl2–CuI-catalyzed8 coupling of the (1S)-
2-iodocyclopenten-1-ol 7 with 1-undecyne (Scheme 2). Protection
onol A 1. Osmylation of 2 proceeded entirely from the
a
-face of the
double bond, as expected, leading to 10 as the only product with
the requisite stereocenters in 84% yield. Finally, treatment of com-
pound 10 with TBAF in THF at room temperature furnished the tar-
9
of the hydroxyl group as its tert-butyldiphenylsilyl ether 4 pro-
get natural product (+)-heliconol A 1 in 96% yield. The
vided sufficient steric bulk on the
a
-face such that osmylation of
spectroscopic and analytical data (1H and 13C NMR) of synthetic
4 proceeded entirely from the opposite side. The resulting diol 3
was selectively oxidized under Swern conditions10 to a ketone;
protection of the tertiary hydroxyl group as its tert-butyl-dimeth-
ylsilyl ether using TBSOTf and 2,6-lutidine in CH2Cl2 at 0 °C pro-
heliconol A {½a 2D5
¼ þ19:6 (c 0.9, acetone)} were identical to those
ꢂ
of natural heliconol A {lit.1
½
a 2D5
ꢂ
¼ þ21:0 (c 1.6, acetone)}.
3. Conclusion
vided
a bulky group on the b-cyclopentane face: enough
conformational freedom was thereby allowed to secure the desired
stereocenter during second osmylation.
In conclusion, we have achieved the total synthesis of (+)-helic-
onol A starting from commercially available cyclopentenone and
employing stereoselective reduction of a ketone, face selective
dihydroxylation, Sonogashira coupling reaction, and a cis-selective
reduction as the key reactions in part of a 10 steps linear sequence
proceeding in 26% overall yield. Following the same strategy one
can achieve the total synthesis of (ꢀ)-heliconol A as a single
isomer.
Ph
N
O
O
Ph
B
Me
O
I
I2, Py, CCl4
0 oC-rt, 78%
BH3.THF, THF
THF, 0-5oC, 85%
5
6
4. Experimental
4.1. General
OH
OH
Pd(Ph3P)2Cl2
( )
6
I
CuI, Et3N
TBDPSCl
All chemicals used in this study were purchased from Aldrich,
Fluka, or Lancaster and used as received. All the moisture-sensitive
reactions were performed under an inert atmosphere of either N2
or Ar using dry solvents. Elemental analyses were recorded on
Elmentar-Vario-EL (Heraeus Company Ltd Germany). The NMR
spectra were obtained on a Bruker 200, 400, or 500 Fourier trans-
form spectrometer. Optical rotations were measured with a JASCO
DIP 370 digital polarimeter. All reactions are monitored by Thin
Layer Chromatography (TLC) carried out on 0.25 mm E-Merck sil-
ica gel plates (60F-254) with UV, I2 or anisaldehyde in ethanol as
development reagents.
1-undecyne, rt
95%
imidazole, DMF
rt, 98%
7
8
OTBDPS
OTBDPS
OH
( )
( )
6
6
OsO4, NMO
acetone, H2O
rt, 90%
3
4
OH
Scheme 2. Synthesis of intermediate 3.
4.1.1. (S)-2-Iodocyclopent-2-enol 7
Our next task was to reduce the alkyne functionality in a cis-
selective manner. Toward this end, Lindlar-catalyzed11 partial
hydrogenation of 9 afforded the Z-olefin in only 10% yield (by 1H
NMR analysis). Extensive optimization was conducted to effect
conversion to Z-olefin 2 by treatment with Pd/C in ethyl acetate
under a hydrogen atmosphere in 95% yield (Scheme 3). With the
intermediate 2 in hand, the stage was set for the synthesis of helic-
To
a solution of (R)-2-methyl-CBS-oxazaborolidine (0.61 g,
2.19 mmol) in THF (15 mL) at 0 °C were added sequentially solu-
tions of 6 (4.55 g, 21.9 mmol) in THF (20 mL) and BH3ꢁTHF
(13.13 mL, 13.13 mmol, 1.0 M in THF) dropwise. The reaction mix-
ture was then stirred at 5 °C for 30 min, then quenched by the
addition of aqueous buffer (pH 7, 10 mL), followed by 30% H2O2
1. Oxaloyl chloride
DMSO, Et3N
-78 oC-rt, 80%
OTBDPS
OH
( )
OTBDPS
OTBS
6
( )
6
2. TBSOTf
2,6-lutidine,
CH2Cl2, 0 oC
72%
O
OH
9
3
OTBS
OTBDPS
OTBS
OH
TBDPSO
OsO4, NMO
acetone, H2O
rt, 84%
H2, Pd/C
( )
( )
7
7
EtOAc, rt
95%
O
O
2
10
OH
HO
OH
OH
OH
TBAF, THF
rt, 96%
O
1 heliconol A
Scheme 3. Synthesis of (+)-heliconol A.

1570
D. K. Mohapatra et al. / Tetrahedron: Asymmetry 19 (2008) 1568–1571
(5 mL). After stirring for 30 min, ethyl acetate (30 mL) was added.
The layers were separated; the organic layer was washed succes-
sively with 1M HCL (10 mL), H2O (10 mL), saturated NaHCO3 solu-
tion (10 mL), and brine (10 mL); then finally dried over Na2SO4,
concentrated in vacuo to leave a residue, which on silica gel col-
umn chromatography (EtOAc/light petroleum, 1:19) yielded 7
(3.9 g, 85%) as a white solid. Recrystallization from ether–pentane
afforded 7 as colorless crystals, mp 61.2–61.6 °C; the enantiomeric
purity was determined to be 96% [HPLC, Column: Kromacil 5-Cel-
arated, and the aqueous layer was extracted with ethyl acetate
(3 ꢃ 20 mL). The combined organic layers were dried over Na2SO4,
and concentrated under reduced pressure to leave a residue, which
on silica gel column purification (EtOAc/light petroleum, 1:6) fur-
nished 3 as a colorless liquid (1.15 g, 90%). ½a D25
¼ ꢀ9:2 (c 1.5,
ꢂ
CHCl3); IR (CHCl3): 3484, 2401, 1600, 1427, 1215, 929, 758 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 0.89 (t, J = 6.8 Hz, 3H), 1.10 (s, 9H),
1.28 (m, 9H), 1.37–1.40 (m, 2H), 1.47–1.54 (m, 4H), 1.82–1.91
(m, 2H), 2.08 (m, 1H), 2.23 (t, J = 7.2 Hz, 2H), 4.23 (dd, J = 4.9,
7.0 Hz, 2H), 7.36–7.43 (m, 6H), 7.68 (dd, J = 1.3, 7.9 Hz, 2H), 7.77
(dd, J = 1.4, 7.9 Hz, 2H); 13C NMR (50 MHz, CDCl3): d 14.2, 19.0,
19.3, 22.7, 26.9, 27.0, 27.8, 28.7, 29.0, 29.2, 29.3, 29.5, 31.9, 77.6,
78.5, 79.3, 79.8, 87.5, 127.6, 129.6, 133.8, 134.3, 135.8, 136.0;
ESI-MS m/z 529.587 (M+Na)+. Anal. Calcd for C32H46O3Si: C,
75.84; H, 9.15. Found: C, 75.71; H, 9.26.
luCoat (250 ꢃ 4.6 mm, 5
l
); Eluent: IPA: PE 01:99; Flow Rate:
¼ ꢀ25:5 (c 1.0, CHCl3); IR (CHCl3): 3583, 2851,
1H NMR (200 MHz, CDCl3): d 1.89 (m, 1H),
0.5 mL/min]. ½a 2D5
ꢂ
1604, 1215, 756 cmꢀ1
;
2.26–2.38 (m, 2H), 2.50 (m, 1H), 4.70 (m, 1H), 6.28 (t, J = 2.41 Hz,
1H); 13C NMR (50 MHz, CDCl3): d 31.4, 32.8, 82.2, 100.4, 142.5;
ESI-MS m/z 227.2 (M+Na)+. Anal. Calcd for C5H7IO: C, 28.60; H,
3.36. Found: C, 28.48; H, 3.20.
4.1.5. (2R,3S)-3-(tert-Butyldiphenylsilyloxy)-2-hydroxy-2-
(undec-1-ynyl)cyclopentanone
4.1.2. (S)-2-(Undec-1-ynyl)cyclopent-2-enol 8
To a solution of 7 (0.9 g, 4.3 mmol) in Et3N (15 mL), were simul-
taneously added Pd(Ph3P)2Cl2 (0.3 g, 0.43 mmol) and CuI (0.163 g,
0.86 mmol) at room temperature, and the reaction mixture was de-
gassed with argon. 1-Undecyne (0.98 g, 6.43 mmol) in Et3N
(10 mL) was then added dropwise, and the reaction mixture was
again degassed under a stream of argon. After stirring for 1 h, the
reaction mixture was filtered; the filtrate was concentrated and
residue was purified by silica gel column chromatography
(EtOAc/light petroleum, 1:19) to give 8 as a colorless liquid
To a solution of oxalyl chloride (0.96 mL, 1.9 mmol, 2 M in
CH2Cl2) in dry CH2Cl2 (10 mL) at ꢀ78 °C was added a solution of
dry DMSO (0.3 mL, 3.85 mmol) in CH2Cl2 (2 mL). After stirring for
30 min at that temperature, diol 3 (0.65 g, 1.3 mmol) in CH2Cl2
(5 mL) was added dropwise. Stirring was continued for 24 h after
which Et3N (0.8 mL, 5.8 mmol) was added slowly and stirred for
30 min before warming it to room temperature. The reaction mix-
ture was then diluted with water (10 mL) and the aqueous layer
was extracted with CH2Cl2 (3 ꢃ 30 mL). The combined organic lay-
ers were dried over Na2SO4 and concentrated. Purification by silica
gel column chromatography (EtOAc/light petroleum, 1:9) afforded
(0.93 g, 95%). ½a D25
ꢂ
¼ ꢀ23:0 (c 1.4, CHCl3); IR (CHCl3): 3492, 2223,
1669, 1557, 1214, 1051, 861 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d
0.88 (t, J = 6.5 Hz, 3H), 1.27 (m, 10H), 1.52–1.59 (m, 3H), 1.68–
1.86 (m, 2H), 2.25–2.39 (m, 4H), 2.51 (m, 1H), 4.74 (m, 1H), 6.08
(t, J = 2.5 Hz, 1H); 13C NMR (50 MHz, CDCl3): d 14.0, 19.5, 22.6,
28.7, 28.9, 29.1, 29.2, 29.4, 30.5, 31.8, 32.6, 75.7, 78.9, 93.2,
128.7, 137.8; ESI-MS m/z 257.28 (M+Na)+. Anal. Calcd for
the keto-derivative (0.52 g, 80%) as a colorless oil. ½a D25
ꢂ
¼ ꢀ2:0 (c
1.3, CHCl3); IR (CHCl3): 3458, 2409, 1758, 1471, 757 cmꢀ1
;
1H
NMR (200 MHz, CDCl3): d 0.87 (t, J = 6.5 Hz, 3H), 1.10 (s, 9H),
1.25 (m, 10H), 1.47–1.58 (m, 2H), 1.83–2.11 (m, 5H), 2.27 (t,
J = 7.03 Hz, 2H), 2.55 (m, 1H), 4.10 (dd, J = 6.9, 8.73 Hz, 1H), 7.33–
7.44 (m, 6H), 7.69–7.79 (m, 4H); 13C NMR (100 MHz, CDCl3): d
14.1, 19.0, 19.4, 22.6, 26.5, 26.8, 28.5, 28.7, 29.1, 29.3, 29.5, 31.9,
32.6, 74.2, 78.1, 78.3, 91.5, 127.6, 129.8, 133.1, 134.0, 135.8,
136.0, 210.3; ESI-MS m/z 527.98 (M+Na)+. Anal. Calcd for
C16H26O: C, 81.99; H, 11.18. Found: C, 81.83; H, 10.96.
4.1.3. (S)-tert-Butyldiphenyl(2-(undec-1-ynyl)cyclopent-2-
enyloxy)silane 4
Imidazole (0.44 g, 6.4 mmol) was added to a solution of 8
(0.75 g, 3.2 mmol) in DMF (10 mL) at room temperature. The reac-
tion flask was cooled to 0 °C and then TBDPSCl (1.3 mL, 4.8 mmol)
was added dropwise. The reaction mixture was stirred overnight at
room temperature. After completion of the reaction, (monitored by
TLC), it was quenched with water (30 mL) and extracted with ether
(2 ꢃ 20 mL). The combined organic layers were dried over Na2SO4
and concentrated to give a residue, which was purified on silica gel
column chromatography eluting with EtOAc/light petroleum
C32H44O3Si: C, 76.14; H, 8.79. Found: C, 75.98; H, 8.84.
4.1.6. (2R,3S)-2-(tert-Butyldimethylsilyloxy)-3-(tert-
butyldiphenylsilyloxy)-2-(undec-1-ynyl)cyclopentanone 9
To a solution of the keto-derivative (0.38 g, 0.76 mmol) in
CH2Cl2 (10 mL) at 0 °C was added 2,6-lutidine (0.2 mL, 1.53 mmol)
followed by TBSOTf (0.3 mL, 1.14 mmol). The reaction mixture was
stirred for 30 min and then quenched with water (5 mL). The layers
were separated and the aqueous layer was extracted with CH2Cl2
(3 ꢃ 20 mL). The combined layers were dried over Na2SO4, concen-
trated and purified on silica gel column chromatography (EtOAc/
light petroleum, 1:19) to yield 9 as a colorless liquid (0.34 g,
(1:19) to provide
¼ ꢀ45:6 (c 1.9, CHCl3); IR (CHCl3): 2856, 2211, 1716, 1464,
1217, 757 cmꢀ1 1H NMR (200 MHz, CDCl3): d 0.88 (t, J = 6.4 Hz,
4 as a colorless liquid (1.49 g, 98%).
½ ꢂ
a 2D5
;
3H), 1.09 (s, 9H), 1.26 (m, 11H), 1.40–1.49 (m, 3H), 1.68 (m, 1H),
1.86 (m, 1H), 2.08–2.41 (m, 4H), 4.81 (t, J = 6.3 Hz, 1H), 6.03 (t,
J = 2.6 Hz, 1H), 7.31–7.40 (m, 6H), 7.68–7.80 (m, 4H); 13C NMR
(50 MHz, CDCl3): d 14.2, 19.3, 19.6, 22.7, 27.0, 28.8, 29.1, 29.3,
29.4, 29.5, 30.3, 31.9, 33.9, 76.9, 80.0, 93.0, 127.3, 127.5, 129.1,
129.4, 129.5, 134.1, 134.7, 136.0, 136.2, 137.6; ESI-MS m/z 495.17
(M+Na)+. Anal. Calcd for C32H44OSi: C, 81.29; H, 9.38. Found: C,
81.25; H, 9.32.
72%). ½a 2D5
ꢂ
¼ þ6:6 (c 1.5, CHCl3); IR (CHCl3): 2930, 2401, 1760,
1428, 1215 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d 0.07 (s, 3H), 0.10
(s, 3H), 0.73 (s, 9H), 0.77 (t, J = 5.0 Hz, 3H), 0.96 (s, 9H), 1.15 (m,
10H), 1.34–1.44 (m, 3H), 1.57–1.67 (m, 2H), 1.88–2.32 (m, 5H),
4.04 (t, J = 5.5 Hz, 1H), 7.21–7.33 (m, 6H), 7.59–7.65 (m, 4H); 13C
NMR (50 MHz, CDCl3): d ꢀ3.1, ꢀ2.8, 14.2, 18.2, 19.1, 19.4, 22.7,
25.8, 26.8, 26.9, 28.4, 29.1, 29.2, 29.3, 29.5, 29.7, 31.9, 75.7, 77.3,
78.9, 91.7, 127.6, 127.7, 129.7, 129.8, 133.4, 134.4, 135.9, 136.0,
209.3; ESI-MS m/z 636.57 (M+NH4)+. Anal. Calcd for C38H58O3Si2:
C, 73.73; H, 9.44. Found: C, 73.48; H, 9.32.
4.1.4. (1S,2S,5S)-5-(tert-Butyldiphenylsilyloxy)-1-(undec-1-
ynyl)-cyclopentane-1,2-diol 3
OsO4 (0.4 mL, 0.008 mmol, 0.02 M in toluene) was added to a
solution of 4 (1.2 g, 2.54 mmol) and NMO (1.2 mL, 5.0 mmol, 50%
aqueous solution) in acetone/water (4:1, 20 mL) at room tempera-
ture. The mixture was stirred overnight and then quenched with a
saturated solution of sodium sulfite (10 mL). The layers were sep-
4.1.7. (2R,3S,Z)-2-(tert-Butyldimethylsilyloxy)-3-(tert-
butyldiphenylsilyloxy)-2-(undec-1-enyl)cyclopenta-none 2
Compound 9 (0.21 g, 0.34 mmol) was hydrogenated in ethyl
acetate (7 mL) with 10% Pd/C (50 mg) at atmospheric pressure.
After stirring for 1 h, (completion of reaction was monitored by

D. K. Mohapatra et al. / Tetrahedron: Asymmetry 19 (2008) 1568–1571
1571
TLC), the reaction mixture was filtered over a pad of Celite, concen-
trated and purified on silica gel column chromatography eluting
with EtOAc/light petroleum (1:19) yielding olefin 2 as a colorless
mixture was stirred for 30 min at room temperature. After comple-
tion (monitored by TLC), the reaction was quenched with a satu-
rated solution of NH4Cl (1 mL) and ethyl acetate (2 mL). The
layers were separated and the aqueous layer was extracted with
ethyl acetate (3 ꢃ 10 mL). The combined organic layers were dried
over Na2SO4, concentrated in vacuo and purified by flash silica gel
chromatography eluting with ethyl acetate/light petroleum (7:3)
liquid (0.2 g, 95%). ½a D25
ꢂ
¼ þ2:4 (c 0.9, CHCl3); IR (CHCl3): 2925,
1758, 1635, 1451, 1086 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d 0.12
(s, 3H), 0.21 (s, 3H), 0.95 (s, 9H), 1.01 (t, J = 6.0 Hz, 3H), 1.16 (s,
9H), 1.38 (m, 13H), 1.81–1.96 (m, 2H), 2.08–2.24 (m, 3H), 2.29–
2.54 (m, 2H), 4.32 (t, J = 5.7 Hz, 1H), 5.74 (dt, J = 5.8, 12.0 Hz, 1H),
5.82 (d, J = 12.0 Hz, 1H), 7.49–7.56 (m, 6H), 7.75–7.84 (m, 4H);
13C NMR (50 MHz, CDCl3): d ꢀ3.4, ꢀ2.6, 14.1, 18.4, 19.3, 22.7,
25.9, 26.8, 26.9, 27.1, 29.2, 29.3, 29.5, 29.5, 29.6, 31.9, 32.9, 79.5,
82.8, 125.1, 127.5, 129.7, 133.1, 135.4, 135.8, 136.0, 136.0, 215.2;
ESI-MS m/z 643.44 (M+Na)+. Anal. Calcd for C38H60O3Si2: C,
73.49; H, 9.74. Found: C, 73.26; H, 9.45.
to afford 1 (heliconol A) as a liquid (0.036 g, 96%). ½a D25
¼ þ19:6
ꢂ
(c 0.9, acetone); IR (CHCl3): 3369, 2925, 2854, 1653, 1464, 1309,
1016 cmꢀ1 1H NMR (400 MHz, DMSO): d 0.84 (t, J = 7.0 Hz, 3H),
;
1.23 (m, 13H), 1.34–1.41 (m, 2H), 1.49–1.59 (m, 3H), 1.77–1.87
(m, 2H), 3.56 (dt, J = 4.4, 7.5 Hz, 1H), 3.72 (t, J = 7.2 Hz, 1H), 4.04
(m, 1H), 4.59 (s, 1H), 5.51 (d, J = 4.0 Hz, 1H), 5.58 (d, J = 6.7 Hz,
1H), 5.85 (s, 1H); 13C NMR (100 MHz, DMSO): d 14.0, 22.2, 25.4,
28.8, 29.0, 29.1, 29.2, 30.6, 31.4, 34.1, 35.1, 80.1, 81.5, 83.3, 84.0,
108.6; ESI-MS m/z 325.16 (M+Na)+. Anal. Calcd for C16H30O5: C,
63.55; H, 10.00. Found: C, 63.46; H, 9.86.
4.1.8. (2R,3R,3aR,4S,6aR)-3a-(tert-Butyldimethylsilyloxy)-4-
(tert-butyldiphenylsilyloxy)-2-nonyl-hexahydro-2H-
cyclopenta[b]furan-3,6a-diol 10
To a solution of 2 (0.12 g, 0.2 mmol) and NMO (0.1 mL,
0.4 mmol, 50% aqueous solution) in acetone/water (4:1, 5 mL)
was added OsO4 (1 mL, 0.02 mmol, 0.02 M in toluene). The reaction
mixture was stirred for 96 h, (completion being monitored by TLC),
then quenched with a saturated solution of sodium sulfite (5 mL).
Ethyl acetate (10 mL) was added and the layers were separated.
The aqueous layer was back extracted with ethyl acetate
(3 ꢃ 20 mL), the combined organic layers were dried over Na2SO4,
concentrated in vacuum and the residue was purified by flash silica
gel column chromatography (EtOAc/light petroleum, 1:19) to
Acknowledgments
B.C. thank UGC, New Delhi, for a research grant. We thank Dr.
Ganesh Pandey for his support and encouragement. We are grate-
ful to Dr. P. R. Rajmohanan for NMR data.
References
1. Mudur, S. V.; Swenson, D. C.; Gloer, J. B.; Campbell, J.; Shearer, C. A. Org. Lett.
2006, 8, 3191–3194.
2. (a) Bauer, A. W.; Kirby, W. M.; Sherris, J. C.; Turck, M. Am. J. Clin. Pathol. 1996,
45, 493–496; (b) Wagenaur, M. M.; Clardy, J. J. Nat. Prod. 2001, 64, 1006–1009.
3. Wicklow, D. T.; Joshi, B. K.; Gamble, W. R.; Gloer, J. B.; Dowd, P. F. Appl. Environ.
Microbiol. 1998, 64, 4482–4484.
afford 10 as a colorless liquid (0.11 g, 84%). ½a D25
¼ þ5:0 (c 1.2,
ꢂ
CHCl3); IR (CHCl3): 3494, 2929, 1662, 1590, 1428, 1113,
970 cmꢀ1 1H NMR (200 MHz, CDCl3): d 0.08 (s, 3H), 0.13 (s, 3H),
;
4. Quan, W.; Yu, B.; Zhang, J.; Liang, Q.; She, X.; Pan, X. Tetrahedron 2007, 63,
9991–9996.
0.83 (s, 9H), 0.87 (t, J = 5.9 Hz, 3H), 1.09 (s, 9H), 1.26 (m, 15H),
1.56–1.73 (m, 4H), 1.89 (m, 1H), 3.09 (br s, 1H), 3.88 (dd, J = 5.96,
12.8 Hz, 1H), 4.03 (t, J = 5.8 Hz, 1H), 4.31 (m, 1H), 4.92 (d,
J = 5.8 Hz, 1H), 7.33–7.45 (m, 6H), 7.66–7.81 (m, 4H); 13C NMR
(50 MHz, CDCl3): d ꢀ3.2, ꢀ2.9, 14.1, 17.7, 19.0, 22.7, 25.7, 26.2,
27.0, 29.3, 29.5, 30.2, 31.9, 34.7, 35.1, 84.0, 84.5, 84.7, 85.7,
109.4, 127.8, 127.8, 130.1, 130.2, 131.7, 133.1, 135.9, 135.9; ESI-
MS m/z 677.15 (M+Na)+. Anal. Calcd for C38H62O5Si2: C, 69.67; H,
9.54. Found: C, 69.73; H, 9.41.
5. Johnson, C. R.; Adams, J. P.; Braun, M. P.; Senanayake, C. B. W.; Wovkulich, P.
M.; Uskokovic´, M. R. Tetrahedron Lett. 1992, 33, 917–918.
6. (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109, 5551–5553;
(b) Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C. P.; Singh, V. K. J. Am. Chem. Soc.
1987, 109, 7925–7926; (c) Deloux, L.; Srebnik, M. Chem. Rev. 1993, 93, 763–
784; (d) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1986–
2012.
7. Johnson, K. R.; Sakaguchi, H. Synlett 1992, 813–816.
8. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467–
4470.
9. Smith, A. B.; Branca, S. J.; Pilla, N. N.; Guaciaro, M. A. J. Org. Chem. 1982, 47,
1855–1869.
10. Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651–1660.
11. Lindlar, H.; Dubuis, R. Organic Syntheses; Wiley: New York, 1973. Collect. Vol. V,
p 880.
4.1.9. (+)-Heliconol A 1
To a solution of 10 (0.082 g, 0.13 mmol) in THF (2 mL) at 0 °C,
TBAF (0.3 mL, 0.3 mmol, 1 M in THF) was added and the reaction