Stereoselective total synthesis of (+)-Varitriol, (-)Varitriol, 5'-epi-(+)-Varitrioiol, and 4'-epi-(-)Varitriol from D-Mannitol

Article abstract of DOI:10.1021/jo100001p

Chemical Equation Presented Stereoselective total syntheses of natural (+)-varitriol (1), (-)-varitriol (2), 5'-epi-(+)-varitriol (3), and 4'-epi-(-)varitriol (4) have been accomplished with use of D-mannitol as a chiral pool material. The Heck reaction was used to assemble the olefinic sugar moiety and the aromatic triflate moiety.

Full text of DOI:10.1021/jo100001p

pubs.acs.org/joc
total syntheses of (þ)- and (-)-varitriol appeared in the
Stereoselective Total Synthesis of (þ)-Varitriol, (-)-
Varitriol, 50-epi-(þ)-Varitriol, and 40-epi-(-)-
Varitriol from D-Mannitol
literature.4 The first total synthesis of (-)-varitriol was
reported by Jennings et al. using cross metathesis to stitch
together the carbohydrate and aromatic moieties.2 Subse-
quently Taylor et al. reported the total synthesis of (-)-
Subhash Ghosh* and Tapan Kumar Pradhan
varitriol, where they used Horner-Wadsworth-Emmons//
4a
€
Ramberg-Backlund sequences. Shaw et al. reported the
Indian Institute of Chemical Technology, Hyderabad 500607,
India
first total synthesis of naturally occurring (þ)-varitriol by
applying a cross metathesis approach.4b In this strategy
D-mannose was used as a chiral pool material for the synth-
esis of the required olefinic sugar moiety. Very recently
subhash@iict.res.in
Received January 1, 2010
Gracza et al. reported another synthetic approach to natural
4c
ꢀ
(þ)-varitriol by applying Kocienski-Julia olefination.
Some simplified analogues of (þ)-varitriol were also re-
ported in the literature.5 In this paper we wish to report
our strategy for the synthesis of (þ)-varitriol, (-)-varitriol,
and their analogues starting from a single chiral pool ma-
terial D-mannitol. The Heck reaction6 was used to introduce
the E-olefinic moiety in the molecule (Scheme 1).
Thus our synthesis commenced from the known diol com-
pound 8, which was prepared from D-mannitol (7) according to
the reported procedures.7 The diol compound 8was converted to
compound 9 in two steps: chemoselective tosylation of the pri-
mary alcohol gave a tosyl intermediate, which on treatment with
LAH in THF at 0 °C furnished secondary alcohol 9in 95% yield
over two steps. Mesylation of 9 with MsCl gave an intermediate
mesyl compound, which on treatment with CSA in MeOH:
CH2Cl2 (1:1) underwent cycloetherification to give tetrahydro-
furan compound 108 in 95% yield. The primary hydroxyl group
of 10 was then protected as its TBS ether to give compound 11,
which on hydrogenation furnished diol compound 12. Introduc-
tion of the double bond between C40 and C50,9 followed by
OsO4-mediated dihydroxylation furnished compound 13 (dr
10:1 in favor of the required isomer) in 55% yield over two
steps. TBS protection of the secondary hydroxyl groups of 13
with TBSOTf followed by selective deprotection of the primary
TBS with HF:Py gave primary alcohol 15, which on DMP10
oxidation followed by Wittig olefination with Ph3PdCH2 gave
olefinic fragment 6. The crucial Heck coupling6d between the
olefinic compound and the aromatic triflate11 was achieved with
Stereoselective total syntheses of natural (þ)-varitriol (1),
(-)-varitriol (2), 50-epi-(þ)-varitriol (3), and 40-epi-(-)-
varitriol (4) have been accomplished with use of D-man-
nitol as a chiral pool material. The Heck reaction was
used to assemble the olefinic sugar moiety and the aro-
matic triflate moiety.
Marine fungi are an important source of a wide range of
biologically active compounds. In 2002 Rosales et al. iso-
lated a low molecular weight cytotoxic compound called
varitriol from the marine-derived strain of the fungus Emeri-
cella variecolor.1 The chemical structure and relative stereo-
chemistry of varitriol was determined by means of detailed
NMR studies. Later the absolute stereochemistry was estab-
lished via total synthesis.2 The cytotoxic activity of this
compound was tested against NCI’s 60-cell panel and it
showed increased potency toward renal, CNS, and breast
cancer cell lines.1,3 Significant cytotoxic activity and un-
known mode of action attracted considerable attention from
synthetic organic chemists worldwide, and as a result several
(4) (a) McAllister, G. D.; Robinson, J. E.; Taylor, R. J. K. Tetrahedron
2007, 63, 12123–12130. (b) Kumar, V.; Shaw, A. K. J. Org. Chem. 2008, 73,
ꢀ
ꢀ
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7526–7531. (c) Palık, M.; Karlubıkova, O.; Lasikova, A.; Kozısek, J.;
Gracza, T. Eur. J. Org. Chem. 2009, 709–715.
(5) (a) Nagarapu, L.; Paparaju, V.; Satyender, A. Bioorg. Med. Chem.
Lett. 2008, 18, 2351–2354. (b) Senthilmurugan, A.; Aidhen, I. S. Eur. J. Org.
Chem. 2010, 555–564.
(6) (a) Heck, R. F. J. Am. Chem. Soc. 1968, 90, 5518–5526. (b) Mizoroki,
T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971, 44, 581–581. (c) Heck,
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R. F.; Nolley, J. P. J. Org. Chem. 1972, 37, 2320–2322. (d) Furstner, A.; Thiel,
O. R.; Kindler, N.; Bartkowska, B. J. Org. Chem. 2000, 65, 7990–7995.
(7) (a) Chakraborty, T. K.; Ghosh, S.; Rao, M. H. V. R.; Kunwar, A. C.;
Cho, H.; Ghosh, A. K. Tetrahedron Lett. 2000, 41, 10121–10125. (b) Ghosh,
S.; Rao, R. V.; Sashidhar, J. Tetrahedron Lett. 2005, 46, 5479–5481.
(8) Chakraborty, T. K.; Das, S.; Raju, T. V. J. Org. Chem. 2001, 66, 4091–
4093.
(9) Garegg, P. G.; Samuclson, B. Synthesis 1979, 813–814.
(10) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277–7287.
(11) (a) Hadfield, A.; Schweitzer, H.; Trova, M. P.; Green, K. Synth.
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Commun. 1994, 24, 1025–1028. (b) Furstner, A.; Thiel, O. R.; Blanda, G. Org.
(1) Malmstrøm, J.; Christophersen, C.; Barrero, A. F.; Oltra, J. E.;
Justica, J.; Rosales, A. J. Nat. Prod. 2002, 65, 364–367.
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Lett. 2000, 2, 3731–3734. (c) Furstner, A.; Konetzki, I. Tetrahedron 1996, 52,
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15071–15078. (d) Furstner, A.; Konetzki, I. J. Org. Chem. 1998, 63, 3072–
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3080. (e) Furstner, A.; Nikolakis, K. Liebigs Ann. 1996, 2107–2113.
(2) Clemens, R. T.; Jennings, M. P. Chem. Commun. 2006, 2720–2721.
(3) Mayer, A. M. S.; Gustafson, K. R. Eur. J. Cancer 2004, 40, 2676–2704.
DOI: 10.1021/jo100001p
r
Published on Web 02/24/2010
J. Org. Chem. 2010, 75, 2107–2110 2107
2010 American Chemical Society

Ghosh and Pradhan
JOCNote
SCHEME 1. Retrosynthetic Analysis
O-methylation followed by reduction of the ester functionality
with DIBAL-H and TBS deprotection furnished (þ)-varitriol,
whose analytical data were in good agreement with the reported
value.4c
For the synthesis of 50-epi-(þ)-varitriol we started from
compound 12. TBS protection of the secondary hydroxyl
groups followed by selective deprotection of the primary
TBS furnished primary alcohol 20. Oxidation of the primary
alcohol with DMP10 gave an aldehyde, which on Wittig
olefination with Ph3PdCH2 in ether gave olefinic compound
21. Heck coupling6d between aromatic triflate 511 and ole-
finic sugar following similar reaction conditions of Scheme 2
afforded compound 22, which was converted to 50-epi-(þ)-
varitriol following the same sort of reactions as used for the
conversion of 16 to (þ)-varitriol (Scheme 3).
SCHEME 2. Synthesis of (þ)-Varitriola
For the synthesis of (-)-varitriol, we started from com-
pound 9, which on benzoylation followed by acetonide
deprotection furnished diol compound 26 (Scheme 4). Selec-
tive tosylation of the primary hydroxyl group gave tosyl
intermediate, which on treatment with K2CO3 in methanol
gave tetrahydrofuran compound 27 in 86% yield over two
steps.12 TBS protection of the primary alcohol followed by
benzyl deprotection via hydrogenation gave diol compound
29, which was converted to ent-13 in two steps. Finally
compound ent-13 was converted to (-)-varitriol (2) follow-
ing the same sort of reactions as were used for the conversion
of 13 to (þ)-varitriol (1).
The synthesis of 40-epi-(-)-varitriol started from com-
pound 29. Global protection of the secondary hydroxyl
groups with TBSOTf gave compound 30. Selective deprotec-
tion of the primary TBS followed by oxidation of the
resulting primary alcohol gave an aldehyde, which was
reacted with Ph3PdCH2 in ether to afford olefinic com-
pound 32. Heck coupling6d between 32 and 5 afforded
compound 33, which was converted to 40-epi-(-)-varitriol
following the same sort of reactions as used earlier for the
synthesis of (þ)-varitriol (Scheme 5).
In conclusion we have developed a strategy for the stereo-
selective total synthesis of (+)-varitriol and its stereochem-
ical analogues. Using this strategy currently we are making
structural analogues for structure activity relationship stu-
dies, which will be reported separately somewhere else.
Experimental Section
Synthesis of Compound 16. To a solution of olefinic com-
pound 6 (86 mg, 0.23 mmol) in dry degassed DMF (5 mL) were
added LiCl (29 mg, 0.69 mmol) and Et3N (0.1 mL, 0.69 mmol)
sequentially under argon atmosphere. Then aromatic triflate 5
(150 mg, 0.46 mmol) followed by Pd(PPh3)2Cl2 (32 mg, 0.046
mmol) were added very quickly and once again the solution was
degassed for 10 min. The reaction mixture was heated to 120 °C
and heating was continued for 10 h. Meanwhile the color of the
reaction mixture became dark brown. After completion of the
reaction, it was quenched with H2O (5 mL). The organic layer
was extracted with EtOAc (50 mL), washed with brine (5 mL),
dried over (Na2SO4), and concentrated in vacuo. The crude
product was purified by column chromatography (4-5% ethyl
acetate in petroleum ether was eluant) to afford compound 16
aReagents and conditions: (i) ref 7; (ii) (a) TsCl, Et3N, CH2Cl2, DMAP
(cat), 0 °C-rt, 2 h; (b) LAH, THF, 0 °C-rt, 10 min, 95% over two steps;
(iii) (a) MsCl, Et3N, CH2Cl2, DMAP (cat), 0 °C-rt, 15 min; (b) CSA,
MeOH:CH2Cl2 (1:1), 0 °C-rt, 2 h, 95%; (iv) TBSCl, Et3N, DMAP (cat),
CH2Cl2, 0 °C-rt, 1 h, 94%; (v) H2, Pd-C, EtOAc, 10 h, 96%; (vi) (a)
TPP, I2 imidazole, toluene, reflux, 30 min; (b) OsO4, NMO, methane
sulfonamide, acetone:H2O (1:1), 40 °C, 3-4 h, dr (10:1), 55% over two
steps; (vii) TBSOTf, CH2Cl2, 2,6-lutidine, 0 °C-rt, 10 min, 87%; (viii)
HF:Py, THF, 10 h, 70%; (ix) (a) DMP, CH2Cl2, NaHCO3, 0 °C-rt, 10
min; (b) Ph3PdCH2, Et2O, (CH3)3COK, 0 °C, 80%; (x) Ar-OTf (5),
PdCl2(PPh3)2, DMF, LiCl, Et3N, 120 °C, 10 h, 80%; (xi) LiOH, THF:
MeOH:H2O (3:1:1), 0 °C-rt, 30 min, 97%; (xii) (a) MeI, acetone,
K2CO3, reflux, 2.5 h; (b) DIBAL-H, CH2Cl2, -78 °C-rt, 10 min, 90%,
over two steps; (xiii) 6 N HCl, THF, 0 °C-rt, 5 h, 88% yield.
(101 mg, 80%) as a colorless liquid. [R]32 +44.69 (c 0.91
D
in CHCl3); IR (neat) 2929, 2857, 2361, 2334, 1737, 1578,
1472, 1382, 1371, 1264, 1211, 1080, 1042, 837 cm-1; 1H NMR
use of Pd(PPh3)2Cl2, LiCl, and Et3N in DMF at 120 °C to give
the compound 16,6b which on treatment with LiOH in MeOH:
THF:H2O (3:1:1) afforded compound 17 in good yield. Finally
(12) Ghosh, S.; Rao, C. N.; Dutta, S. K. Synlett 2007, 1464–1466.
2108 J. Org. Chem. Vol. 75, No. 6, 2010

Ghosh and Pradhan
JOCNote
SCHEME 3. Synthesis of 50-epi-(þ)-Varitriola
SCHEME 5. Synthesis of 40-epi-(-)-Varitriola
aReagent and conditions: (i) TBSOTf, 2,6-lutidine, CH2Cl2, 0 °C, 30
min, 85%; (ii) HF:Py, THF, 7 h, 75%; (iii) (a) DMP, CH2Cl2, NaHCO3,
0 °C-rt, 20 min; (b) Ph3PdCH2, Et2O, (CH3)3COK, 0 °C, 80%; (iv) 5,
PdCl2(PPh3)2, DMF, LiCl, Et3N, 120 °C, 16 h, 87%; (v) LiOH, THF:
MeOH:H2O (3:1:1), 0 °C-rt, 30 min, 92%; (vi) (a) MeI, acetone,
K2CO3, reflux, 1 h; (b) DIBAL-H, CH2Cl2, -78 °C-rt, 10 min, 85%,
over two steps; (vii) 6 N HCl, THF, 3 h, 83% yield.
aReagent and conditions: (i) TBSOTf, 2,6-lutidine, CH2Cl2, 0 °C, 30
min, 98%; (ii) HF:Py, THF, 10 h, 72%; (iii) (a) DMP, CH2Cl2, NaHCO3,
0 °C-rt, 10 min; (b) Ph3PdCH2, Et2O, (CH3)3COK, 0 °C, 80%; (iv) 5,
PdCl2(PPh3)2, DMF, LiCl, Et3N, 120 °C, 10 h, 85%; (v) LiOH, THF:
MeOH:H2O (3:1:1), 0 °C-rt, 1 h, 97%; (vi) (a) MeI, acetone, K2CO3,
reflux, 6-7 h; (b) DIBAL-H, CH2Cl2, -78 °C-rt, 10 min, 88%; over
two steps (vii) 6 N HCl, THF, 10 h, 75% yield.
-4.6; MS (ESI) m/z (%) 549 (20) [M + H]+, 566 (80) [M +
NH4]+, 571 (65) [M + Na]+; HRMS (ESI) calcd for
C29H48O6NaSi2 [M + Na]+ 571.2887, found 571.2892.
Synthesis of Compound 22. 22 was prepared following the same
procedure as used earlier for the synthesis of 16: [R]27D +45.23 (c
0.21 in CHCl3); IR (neat)2929, 2857, 2361, 2334, 1737, 1578, 1472,
1382, 1371, 1264, 1211, 1157, 1103, 1080, 1042, 837, 778 cm-1; 1H
NMR (600 MHz, CDCl3) δ 7.60 (d, J = 16.0 Hz, 1H), 7.39 (t, J =
8.0 Hz, 1H), 7.23 (d, J = 8.1 Hz, 1H), 6.82 (dd, J = 8.1, 1.0 Hz,
1H), 6.27 (dd, J = 16.0, 8.6 Hz, 1H), 4.36 (d, J = 8.6 Hz, 1H), 4.22
(dq, J = 2.5, 6.3 Hz, 1H), 3.96 (br s, 1H), 3.76 (dd, J = 2.7, 1.3 Hz,
1H), 1.69 (s, 3H), 1.66 (s, 3H), 1.25 (d, J = 6.3 Hz, 3H), 0.88 (s,
9H), 0.87 (s, 9H), 0.12 (s, 3H), 0.08 (s, 3H), 0.06 (s, 3H), 0.05 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 160.1, 156.7, 141.5, 134.9,
134.2, 129.0, 121.4, 116.1, 110.8, 105.1, 88.0, 84.2, 80.1, 77.6, 26.2,
25.7, 25.0, 18.0, 17.8, 14.5, -4.4, -4.5, -4.7, -4.9; MS (ESI) m/z
(%) 549 (10) [M + H]+, 566 (90) [M + NH4]+, 571 (75) [M +
Na]+; HRMS (ESI) calcd for C29H48O6NaSi2 [M + Na]+
571.2883, found 571.2890.
SCHEME 4. Synthesis of (-)-Varitriola
Synthesis of Compound 33. 33 was prepared following the
same procedure as used earlier for the synthesis of 16: [R]27
D
aReagent and conditions: (i) (a) BzCl, Et3N, CH2Cl2, DMAP (cat),
0 °C-rt, 8 h,70%, starting material recovered; (ii) CSA, MeOH:CH2Cl2
(1:1), 0 °C-rt, 10 h, 90%; (iii) (a) TsCl, Et3N, CH2Cl2, DMAP (cat),
0 °C-rt, 2 h ; (b) K2CO3, MeOH, 30 min, 86%; (iv) TBSCl, Et3N,
CH2Cl2, DMAP, 0 °C-rt, 4 h, 93%; (v) H2, Pd-C, EtOAc, 3 h, 92%; (vi)
(a) TPP, I2 imidazole, toluene, reflux, 30 min; (b) OsO4, NMO, methane
sulfonamide, acetone:H2O (1:1), 40 °C, 3-4 h, dr (9:1), 56% over two
steps.
+23.65 (c 1.23 in CHCl3); IR (neat) 2930, 2893, 2857, 1737,
1577, 1471, 1383, 1316, 1265, 1209, 1113, 1083, 1050, 933, 836,
776 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.77 (d, J = 16.2 Hz,
1H), 7.43 (t, J = 8.0 Hz, 1H), 7.32 (dd, J = 8.0, 1.0 Hz, 1H), 6.85
(dd, J = 8.0, 1.0 Hz, 1H), 6.33 (dd, J = 16.2, 8.1 Hz, 1H), 4.64
(dd, J = 8.1, 3.0 Hz, 1H), 3.95 (dd, J = 3.0, 1.4 Hz, 1H), 3.91
(dq, J = 1.4, 6.6 Hz, 1H), 3.80 (t, J = 1.4 Hz, 1H), 1.70 (s, 3H),
1.69 (s, 3H), 1.35 (d, J = 6.6 Hz, 3H), 0.91 (s, 9H), 0.87 (s, 9H),
0.09 (s, 3H), 0.08 (s, 3H), 0.06 (s, 3H), -0.03 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 160.2, 156.7, 141.4, 135.0, 131.3, 130.8,
121.4, 116.2, 110.9, 105.1, 84.1, 83.1, 82.8, 81.7, 25.8, 25.7 (2C),
25.3, 19.8, 18.0, 17.9, -4.5, -4.7, -4.8; MS (ESI) m/z (%)
549 (40) [M + H]+, 566 (90) [M + NH4]+, 571 (65) [M + Na]+;
HRMS (ESI) calcd for C29H48O6NaSi2 [M + Na]+ 571.2880,
found 571.2885.
(500 MHz, CDCl3) δ 7.69 (d, J = 15.8 Hz, 1H), 7.44 (t, J = 8.0
Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H),
6.09 (dd, J = 15.8, 6.3 Hz, 1H), 4.49 (ddd, J = 6.3, 3.9, 1.5 Hz,
1H), 4.04 (dq, J = 6.3, 6.1 Hz, 1H), 3.90 (t, J = 3.9 Hz, 1H),
3.73 (dd, J = 6.1, 4.1 Hz, 1H), 1.71 (s, 3H), 1.69 (s, 3H), 1.31
(d, J = 6.3 Hz, 3H), 0.91 (s, 9H), 0.90 (s, 9H), 0.09 (s, 3H), 0.09
(s, 3H), 0.07 (br s, 6H); 13C NMR (150 MHz, CDCl3) δ 159.9,
156.7, 141.5, 135.1, 132.8, 129.9, 121.5, 116.3, 110.9, 105.2, 84.1,
78.2, 77.5, 77.3, 25.8 (2C), 25.3, 19.1, 18.1, -4.2, -4.3, -4.4,
Synthesis of (+)-Varitriol (1). To a stirred solution of com-
pound 18 (14 mg, 0.02 mmol) in THF (2 mL) was added 6 N HCl
J. Org. Chem. Vol. 75, No. 6, 2010 2109

Ghosh and Pradhan
JOCNote
(2 mL) in a dropwise manner at 0 °C. After being stirred for 7 h
at room temperature the reaction was quenched slowly with
saturated NaHCO3 solution (3-4 mL) at 0 °C and the organic
layer was extracted with CHCl3 (4 ꢀ 50 mL), washed with H2O
(2 ꢀ 5 mL) and brine (5 mL), dried over (Na2SO4), and filtered.
After concentration in vacuum, it was subjected to chromato-
graphic purification (preparative TLC, 20% acetone in CH2Cl2
(2 times)) to afford compound 1 (6.7 mg, 88%) as a white solid.
1H), 3.82 (ddd, J = 5.4, 3.8, 2.0 Hz, 1H), 3.80 (s, 3H), 3.48 (d,
J = 4.3 Hz, 1H), 3.01 (d, J = 5.4 Hz, 1H), 2.91 (t, J = 5.8 Hz,
1H), 1.19 (d, J = 6.4 Hz, 1H); 13C NMR (150 MHz, CD3CN) δ
158.8, 138.7, 132.8, 129.7, 128.8, 127.5, 119.2, 110.7, 86.6, 84.1,
80.0, 77.8, 56.2, 55.4, 14.5; MS (ESI) m/z (%) 303 (100) [M þ
Na]þ; HRMS (ESI) calcd for C15H20O5Na [M þ Na]þ 303.1210,
found 303.1202.
Analytical data of compound 40-epi-(-)-varitriol: [R]26D -35.9
(c 0.22 in MeOH); 1H NMR (300 MHz, CD3CN) δ 7.26 (t, J =
8.0 Hz, 1H), 7.16 (dd, J = 7.9, 1.1 Hz, 1H), 7.05 (dd, J = 15.9,
1.1 Hz, 1H), 6.91 (dd, J = 8.0, 1.1 Hz, 1H), 6.22 (dd, J = 15.9,
6.9 Hz, 1H), 4.68 (s, 2H), 4.52 (ddd, J = 6.9, 4.3, 1.2 Hz, 1H),
3.97 (dd, J = 4.3, 2.0 Hz, 1H), 3.84 (s, 3H), 3.78-3.69 (m, 2H),
1.31 (d, J = 6.2 Hz, 3H); 13C NMR (150 MHz, CD3CN) δ 158.4,
138.4, 130.0, 129.4, 129.3, 127.0, 118.9, 110.4, 83.9, 82.4, 81.2,
80.6, 55.8, 55.0, 19.3; MS (ESI) m/z (%) 303 (100) [M þ Na]þ;
HRMS (ESI) calcd for C15H20O5Na [M þ Na]þ 303.1220, found
303.1225.
[R]28 +40.00 (c 0.21 in MeOH); IR (neat) 3375, 2960, 2922,
D
1587, 1575, 1469, 1456, 1439, 1255, 1089, 1004, 974, 799, 748
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.23 (t, J = 8.1 Hz, 1H),
7.09 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 16.1 Hz, 1H), 6.68 (d, J =
8.1 Hz, 1H), 6.09 (dd, J = 16.1, 7.3 Hz, 1H), 4.82 (d, J = 11.7
Hz, 1H), 4.72 (d, J = 11.7 Hz, 1H), 4.29 (t, J = 6.6 Hz, 1H),
3.95-3.81 (m, 5H), 3.69 (t, J = 5.5 Hz, 1H), 3.62 (br s, 1H), 3.08
(br s, 1H), 2.81 (br s, 1H), 1.32 (d, J = 6.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 157.7, 137.3, 131.0, 129.4, 128.9, 125.8,
119.0, 109.7, 84.0, 79.9, 76.1, 75.3, 56.4, 55.6, 19.2; MS (ESI) m/z
(%) 281 (10) [M + H]+, 303 (100) [M + Na]+; HRMS
(ESI) calcd for C15H20O5Na [M + Na]+ 303.1208, found
303.1198.
Acknowledgment. We are thankful to DST, New Delhi,
India for financial support (S.G.) and UGC, New Delhi,
India, (T.K.P.) for research fellowships. We are also thank-
ful to Dr. J. S. Yadav, Director of IICT, Dr. A. C. Kunwar,
and Dr. T. K. Chakraborty Director of CDRI, for their
support and encouragement.
Analytical data of (-)-varitriol (2): [R]30 -42.2 (c 0.135 in
D
MeOH) in good agreement with the value reported by Taylor4a
and Gracza et al.,4c not with the value reported by others;1,2
HRMS (ESI) calcd for C15H20O5Na [M þ Na]þ 303.1210, found
303.1209.
Analytical data of compound 50-epi-(þ)-varitriol: [R]30
D
þ58.75 (c 0.08 in CHCl3); IR (neat, cm-1) 3334, 2922, 2853,
1
2363, 2333, 1740, 1708, 1576, 1464, 1260, 1081, 1044, 992; H
Supporting Information Available: Experimental proce-
dures, and spectral data for compounds 9-15, 6, 17-32, 34,
NMR (600 MHz, CD3CN) δ 7.22 (t, J = 8.0 Hz, 1H), 7.10 (d,
J = 8.0 Hz, 1H), 6.97 (d, J = 15.8 Hz, 1H), 6.87 (d, J = 8.0 Hz,
1H), 6.19 (dd, J = 15.8, 7.3 Hz, 1H), 4.63 (dd, J = 11.7, 5.8 Hz,
1H), 4.62 (dd, J = 11.7, 5.8 Hz, 1H), 4.11 (ddd, J = 7.3, 3.8, 1.1
Hz, 1H), 4.06 (dq, J = 4.0, 6.4 Hz, 1H), 3.85 (dt, J = 2.0, 4.1 Hz,
1
and 35 and the copies of H and 13C NMR spectra for com-
pounds 9-15, 6, 16-18, 1, 19-24, 3, 25-35, and 4. This
material is available free of charge via the Internet at http://
pubs.acs.org.
2110 J. Org. Chem. Vol. 75, No. 6, 2010