Stereoselective total synthesis of ophiocerin C through two different approaches

Article abstract of DOI:10.1002/hlca.201400086

Stereoselective total synthesis of ophiocerin C has been accomplished through two different approaches starting separately from acetaldehyde and from (R)-propylene oxide, and Sharpless asymmetric dihydroxylation has been employed as the key step in both a

Full text of DOI:10.1002/hlca.201400086

Helvetica Chimica Acta – Vol. 97 (2014)
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Stereoselective Total Synthesis of Ophiocerin C through Two Different
Approaches1)
by Malampati Srilatha and Biswanath Das*
Natural Products Chemistry Division, CSIR – Indian Institute of Chemical Technology, Hyderabad-
500007, India (phone: þ 91-40-7193434; fax: þ 91-40-7160512; e-mail: biswanathdas@yahoo.com)
Stereoselective total synthesis of ophiocerin C has been accomplished through two different
approaches starting separately from acetaldehyde and from (R)-propylene oxide, and Sharpless
asymmetric dihydroxylation has been employed as the key step in both approaches.
Introduction. – The tetrahydropyran moiety is found in various natural products
that possess valuable biological properties [1]. Four tetrahydropyran derivatives,
ophiocerins A – D (1 – 4, resp.), have been isolated from the fresh water aquatic fungus
Ophiocerus unezuelense (Magnaporthaceae) [2]. The substitution patterns of these
compounds are interesting, and their synthesis is an important topic in current organic
chemisty [3]. In continuation of our work [4] on the stereoselective syntheses of natural
products, herein we describe the total synthesis of ophiocerin C (3) through two
different approaches.
Results and Discussion. – The retrosynthetic analysis (Scheme 1) indicates that
ophiocerin C (3) can be synthesized from the p-toluenesulfonate 5 [3g], which, in turn,
can be prepared from the allylic alcohol 6. The latter can be obtained either from the
homoallylic alcohol 7, derived from acetaldehyde (8) or from the homopropargyl
alcohol 9, generated from (R)-propylene oxide (¼(R)-2-methyloxirane; 10).
Acetaldehyde (8) was converted to the chiral homoallylic alcohol 7 as described in
t
[5], and the OH group of the latter was protected as BuPh2Si (TBDPS) ether (!11)
[6] by treatment with TBDPSCl and 1H-imidazole (Scheme 2). Compound 11 was
subjected to Sharpless asymmetric dihydroxylation [7] using AD-mix a in tBuOH/H2O
1:1 to produce the diol 12. The diastereoisomers were not separated. The diol 12 was
subsequently treated with NaIO4, and the corresponding aldehyde underwent Wittig
olefination with Ph3PCHCOOEt to form the unsaturated ester 13 [8]. Reduction of 13
1
)
Part 76 in the series ꢂSynthetic Studies on Natural Productsꢃ.
ꢀ 2014 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 97 (2014)
Scheme 1. Retrosynthetic Analysis
with DIBAL afforded the common intermediate, the allylic alcohol 6, in good yield.
The reaction sequences involving 11 to 13, and 13 to 6 have been described in [6].
However, we used AD-mix a for dihydroxylation of the C¼C bond of 11, though in
the next step the chirality has been destroyed. The reason for using AD-mix a was
that the reaction is pretty easy, and potassium osmate (a constituent of AD-mix a) is
far less volatile and less unpleasant compared to OsO4. The yield of the reaction was
also high.
The allylic alcohol 6 was also prepared from (R)-propylene oxide (¼(R)-2-
methyloxirane; 10; Scheme 2). The latter was treated with the alkyne
HCꢀCCH2OPMB in the presence of BuLi and BF3 · OEt2 to furnish the homopro-
pargyl alcohol 9. The free OH group of 9 was protected as TBDPS ether 14, and the
PMB group of 14 was removed with DDQ to generate the propargyl alcohol 15 [9].
Subsequent reduction of 15 with Red-Al afforded the intermediate allylic alcohol 6
required for further steps. A reaction analogous to 10 ! 6 has been reported earlier
using a different protecting group [9]. The OH group of 6 was protected as the PMB
ether 16 by treatment with PMBCl and NaH. To generate the diol with required
configuration, 16 was again subjected to Sharpless asymmetric dihydroxylation using
t
AD-mix a in BuOH/H2O 1:1 to furnish the diol 17 along with its one minor
diastereoisomer. The required major diol 17 was separated from its diastereoisomer
(diastereomer ratio (dr) 93 :7) and used for further steps. The two OH groups of 17
were protected by preparing the acetonide 18 by treatment with 2,2-dimethoxypropane
and TsOH, and the PMB group of 18 was removed by reaction with DDQ to form the
alcohol 19. Tosylation of 19 with TsCl gave compound 20, which, on treatment with
Bu4NF yielded the desired p-toluenesulfonate 5. Finally, cyclization of 5 with tBuOK,
followed by removal of the acetonide group with TsOH, afforded ophiocerin C (3). It
should be mentioned here that the analogous reaction steps for the conversion of 6 to 5
and for the cyclization of 5 to 3 were used earlier for the synthesis of ophiocerin B (2)
[3g]. The physical and spectroscopic properties of the synthesized ophiocerin C (3)
were found to be identical to those reported for the naturally occurring compound [2].
In conclusion, we have described the total stereoselective synthesis of ophiocerin C
(3) through two different approaches starting separately from a nonchiral compound,
acetaldehyde (8) and a chiral compound, (R)-propylene oxide (10).
The authors thank UGC and CSIR, New Delhi, for financial support.

Helvetica Chimica Acta – Vol. 97 (2014)
Scheme 2. Synthesis of Ophiocerin C (3)
1579
a) tBuPh2SiCl (TBDPSCl), 1H-imidazole, cat. 4-(dimethylamino)pyridine (DMAP), CH2Cl2, 08 to r.t.,
3 h; 90%. b) AD-mix a, MeSO2NH2, tBuOH/H2O 1:1, 08, 8 h; 82%. c) 1. NaIO4, Et2O/H2O 3 :1, r.t., 2 h;
2. Ph3P¼CHCOOEt, CH2Cl2, r.t., 8 h; overall yield 84%. d) Diisobutylaluminium hydride (DIBAL),
CH2Cl2, ꢁ 788, 1 h; 92%. e) 4-Methoxybenzyl (PMB)-protected propargyl alcohol (prop-2-yn-1-ol),
BuLi, BF3 · Et2O, dry THF, ꢁ 788, 3 h; 85%. f) TBDPSCl, 1H-imidazole, cat. DMAP, CH2Cl2, 08 to r.t.,
4 h; 91%. g) 2,2-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), CH2Cl2/H2O 9 :1, 08 to r.t., 30 min;
86%. h) Red-Al, dry THF, 08 to r.t., 2 h; 72%. i) NaH, 4-Methoxybenzyl chloride (PMBCl), dry THF, 08
to r.t., 6 h; 86%. j) AD-mix a, MeSO2NH2, tBuOH/H2O 1:1, 08, 24 h; 81%. k) 2,2-Dimethoxypropane,
TsOH (cat.), CH2Cl2, r.t., 2 h; 92%. l) DDQ, CH2Cl2/H2O 9 :1, 08 to r.t., 30 min; 84%. m) TsCl, Et3N, cat.
DMAP, CH2Cl2, r.t., 3 h; 89%. n) Bu4NF (TBAF), THF, 08 to r.t., 2 h; 85%. o) 1. tBuOK, Et2O, 08, 2 h; 2.
TsOH (cat.), MeOH, r.t., 2 h; 79% (two steps).
Experimental Part
General. All commercially available reagents were used directly without further purification unless
otherwise stated. The solvents used were all of AR (anal. reagent) grade and were distilled under dry N2
where necessary. All reactions were performed in pre-dried apparatus unless otherwise stated. The
progress of the reactions was monitored by anal. TLC performed on Merck silica-gel 60 F254 plates. Yields
were of purified compounds unless otherwise stated. Column chromatography (CC): silica gel 60 – 120
mesh (Qingdao Marine Chemical, P. R. China). Optical rotations: JASCO DIP 300 digital polarimeter.
NMR Spectra: VARIAN Gemini 200 MHz spectrometer with TMS as internal standard in CDCl3; d in
ppm and J in Hz. ESI-MS: WATERS/MICROMASS VG-Autospec apparatus. HR-MS: QSTAR XL,
hybrid LC/MS/MS system (Applied Biosystems).
(tert-Butyl)[(2R)-pent-4-en-2-yloxy]diphenylsilane (11). To a stirred soln. of 7 (500 mg, 5.81 mmol)
in dry CH2Cl2 (15 ml), 1H-imidazole (593 mg, 8.72 mmol) and cat. amount of DMAP were added at 08,
and the mixture was stirred for 20 min. Then, TBDPSCl (1.51 ml, 5.813 mmol) was added at 08. The
mixture was warmed to r.t., stirred for 3 h, and then diluted with CH2Cl2 (40 ml). The org. layer was

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Helvetica Chimica Acta – Vol. 97 (2014)
washed with brine (10 ml), dried (Na2SO4), and concentrated, and the residue was subjected to CC to
give 11 (1.69 g, 90%). Spectroscopic data: see [6].
(2S,4R)-4-[(tert-Butyl)diphenylsilyloxy]pentane-1,2-diol (¼2-O-[(tert-Butyl)(diphenyl)silyl]-1,3-di-
t
deoxy-d-threo-pentitol; 12). To a stirred soln. of 11 (1.6 g, 4.94 mmol) in BuOH/H2O 1:1 (30 ml),
MeSO2NH2 (50 mg, 0.51 mmol), and AD-mix a (6.91 g) were added at 08, and the mixture was stirred for
8 h at the same temp. After completion, the reaction was quenched with Na2SO3, the mixture was stirred
for another 20 min, and filtered over a Celite pad. The residue was extracted with AcOEt (2 ꢂ 20 ml). The
combined org. layers were washed with brine (5 ml), dried (Na2SO4), and concentrated. The residue was
1
purified by CC to obtain 12 (1.44 g, 82%). IR: 3407, 2960, 2931, 2858, 1108, 704. H-NMR (200 MHz,
CDCl3): 7.88 – 7.64 (m, 4 H); 7.49 – 7.32 (m, 6 H); 4.22 – 4.01 (m, 2 H); 3.93 (br. s, 1 H); 3.59 – 3.33 (m,
2 H); 3.22 (br. s, 1 H); 1.81 – 1.63 (m, 2 H); 1.02 (s, 9 H); 1.00 (d, J ¼ 7.0, 3 H). 13C-NMR (50 MHz,
CDCl3): 135.9; 134.0; 129.9; 127.8; 68.7; 68.0; 64.5; 42.1; 27.0; 22.2; 18.8. ESI-MS: 381 ([M þ Na]þ). Anal.
calc. for C21H30O3Si (358.55): C 70.35, H 8.43; found: C 70.29, H 8.41.
Ethyl (2E,5R)-5-{[(tert-Butyl)(diphenyl)silyl]oxy}hex-2-enoate (13). To a stirred soln. of 12 (1.3 g,
3.63 mmol) in Et2O/H2O 3 :1 (10 ml) at 08, NaIO4 (1.55 g, 7.26 mmol) was added slowly in portions. The
mixture was warmed to r.t., stirred for 2 h, and then the reaction was quenched with NaHCO3 (10 ml)
slowly. The org. layer was separated, washed with brine (5 ml), dried (Na2SO4), and concentrated. The
aldehyde was used immediately for the next step. To a stirred soln. of aldehyde (1.10 g, 3.37 mmol) in dry
CH2Cl2 (12 ml), ethyl (triphenyl-l5-phosphanylidene)acetate (1.40 g, 4.04 mmol) was added, and the
mixture was stirred at r.t. for 8 h. It was then concentrated, and the residue was purified by CC to yield 13
(1.2 g, 84%). Spectroscopic data: see [6].
(2E,5R)-5-{[(tert-Butyl)(diphenyl)silyl]oxy}hex-2-en-1-ol (6). For synthetic procedure and spectro-
scopic data, see [6].
(2R)-6-[(4-Methoxybenzyl)oxy]hex-4-yn-2-ol (9). To a stirred soln. of PMB-protected propargyl
alcohol (¼ prop-2-yn-1-ol; 3.33 g, 18.96 mmol) in dry THF (2 ꢂ 20 ml), BuLi (1.6m in hexane, 16.16 ml,
25.86 mmol) was added under N2 at ꢁ 788, and the mixture was stirred for 30 min. The mixture was
sequentially treated with BF3 · OEt2 (2.55 ml, 20.68 mmol) and a soln. of (R)-2-methyloxirane 10 (1.2 ml,
17.24 mmol) in dry THF at 10-min intervals and stirred for 3 h at the same temp. The reaction was
quenched with sat. aq. NH4Cl (30 ml). The resulting mixture was diluted with AcOEt (2 ꢂ 20 ml),
washed with H2O (20 ml) and brine (10 ml), dried (Na2SO4), and concentrated. The residue was purified
by CC to obtain 9 (3.43 g, 85%). [a]2D7 ¼ ꢁ5.8 (c ¼ 1.0, CHCl3). IR: 3446, 2931, 2859, 1513, 1248, 1073.
1H-NMR (200 MHz, CDCl3): 7.30 (d, J ¼ 8.0, 2 H); 6.88 (d, J ¼ 8.0, 2 H); 4.52 (s, 2 H); 4.12 (s, 2 H); 3.93
(m, 1 H); 3.80 (s, 3 H); 2.49 – 2.23 (m, 3 H); 1.24 (d, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 159.4;
129.6; 129.5; 113.2; 83.0; 78.1; 71.0; 65.9; 57.1; 55.2; 29.2; 22.1. ESI-MS: 257 ([M þ Na]þ). Anal. calc. for
C14H18O3 (234.29): C 71.77, H 7.74; found: C 71.70, H 7.69.
(tert-Butyl)({(2R)-6-[(4-methoxybenzyl)oxy]hex-4-yn-2-yl}oxy)diphenylsilane (14). Compound 14
was prepared as described for 11. Yield: 6.27 g (91%). [a]2D7 ¼ þ12.1 (c ¼ 2.0, CHCl3). IR: 3447, 2958,
2931, 2857, 1108, 703. 1H-NMR (200 MHz, CDCl3): 7.74 – 7.65 (m, 4 H); 7.48 – 7.32 (m, 6 H); 7.26 (d, J ¼
8.0, 2 H); 6.89 (d, J ¼ 8.0, 2 H); 4.49 (s, 2 H); 4.09 (s, 2 H); 3. 98 (m, 1 H); 3.80 (s, 3 H); 2.45 – 2.24 (m,
2 H); 1.21 (d, J ¼ 7.0, 3 H); 1.05 (s, 9 H). 13C-NMR (50 MHz, CDCl3): 159.2; 136.1; 136.0; 134.2; 129.8;
128.7; 113.4; 84.0; 77.9; 71.2; 68.8; 57.2; 55.0; 29.4; 27.3; 23.2; 19.1. ESI-MS: 495 ([M þ Na]þ). Anal. calc.
for C30H36O3Si (472.69): C 76.23, H 7.68; found: C 76.20, H 7.64.
(5R)-5-{[(tert-Butyl)(diphenyl)silyl]oxy}hex-2-yn-1-ol (15). To a stirred soln. of 14 (6.0 g,
12.71 mmol) in CH2Cl2/H2O 9 :1 (40 ml), DDQ (3.46 g, 15.25 mmol) was added at 08, and the soln.
was stirred for 20 min at r.t. The reaction was quenched with sat. NaHCO3 soln. (20 ml), and the mixture
was extracted with CH2Cl2 (2 ꢂ 20 ml), and washed with H2O (20 ml) and brine (10 ml). The combined
org. layers were dried (Na2SO4), concentrated, and purified by CC to obtain 15 (3.84 g, 86%).
Spectroscopic data: see [9].
(2E,5R)-5-{[(tert-Butyl)(diphenyl)silyl]oxy}hex-2-en-1-ol (6). For synthetic procedure and spectro-
scopic data see ref. [9].
(tert-Butyl)({(2R,4E)-6-[(4-methoxybenzyl)oxy]hex-4-en-2-yl}oxy)diphenylsilane (16). Compound
6 (2.5 g, 7.06 mmol) in dry THF (5 ml) was added to a suspension of NaH (310 mg, 7.76 mmol) in THF
(20 ml) under N2 at 08, and the mixture was stirred for 30 min. Then, a soln. of PMBCl (1.14 g, 8.47 mmol)

Helvetica Chimica Acta – Vol. 97 (2014)
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was added, and the mixture was stirred for 6 h at r.t. The reaction was quenched with sat. aq. NH4Cl
(10 ml) soln., and the mixture was extracted with AcOEt (2 ꢂ 20 ml). The org. layer was washed with
H2O (10 ml) and brine (5 ml), dried (Na2SO4), evaporated, and purified by CC to obtain 16 (2.88 g,
1
86%). [a]2D7 ¼ ꢁ10.2 (c ¼ 0.5, CHCl3). IR: 3450, 2931, 2856, 1512, 1246, 1106, 703. H-NMR (200 MHz,
CDCl3): 7.73 – 7.65 (m, 4 H); 7.48 – 7.32 (m, 6 H); 7.31 – 7.23 (m, 2 H); 6.92 – 6.82 (m, 2 H); 5.70 – 5.49 (m,
2 H); 4.51 – 4.38 (m, 4 H); 3.90 (m, 1 H); 3.81 (s, 3 H); 2.28 – 2.14 (m, 2 H); 1.09 (d, J ¼ 7.0, 3 H); 1.03 (s,
9 H). 13C-NMR (50 MHz, CDCl3): 159.4; 136.1; 134.8; 129.2; 129.0; 128.8; 127.3; 127.1; 113.3; 71.2; 70.3;
68.4; 55.2; 42.1; 27.2; 22.2; 19.0. ESI-MS: 497 ([M þ Na]þ). Anal. calc. for C30H38O3Si (474.71): C 75.90, H
8.07; found: C 75.88, H 8.02.
5-O-[(tert-Butyl)(diphenyl)silyl]-4,6-dideoxy-1-O-(4-methoxybenzyl)-d-xylo-hexitol (17). Com-
pound 17 was prepared as described for 12. Yield: 2.34 g, 81%. [a]2D7 ¼ ꢁ1.4 (c ¼ 0.4, CHCl3). IR:
3448, 2929, 2857, 1632, 1108, 766. 1H-NMR (200 MHz, CDCl3): 7.75 – 7.68 (m, 4 H); 7.47 – 7.33 (m, 6 H);
7.22 (d, J ¼ 8.0, 2 H); 6.88 (d, J ¼ 8.0, 2 H); 4.50 – 4.44 (m, 2 H); 4.23 – 4.01 (m, 2 H); 3.80 (s, 3 H); 3.58 –
3.46 (m, 3 H); 1.84 – 1.78 (m, 2 H); 1.08 (s, 9 H); 1.02 (d, J ¼ 7.0, 3 H). 13C-NMR (50 MHz, CDCl3): 136.2;
134.9; 130.0; 129.8; 129.6; 127.5; 114.2; 73.1; 71.7; 70.2; 69.1; 68.8; 54.8; 40.7; 26.3; 19.6. ESI-MS: 531
([M þ Na]þ). Anal. calc. for C30H40O5Si (508.72): C 70.83, H 7.93; found: C 70.76, H 7.90.
5-O-[(tert-Butyl)(diphenyl)silyl]-4,6-dideoxy-1-O-(4-methoxybenzyl)-2,3-O-(1-methylethylidene)-
d-xylo-hexitol (18). To a stirred soln. of 17 (2.2 g, 4.33 mmol) in CH2Cl2 (20 ml), Me2C(OMe)2 (0.63 ml,
5.19 mmol) and TsOH (cat.) were added, and the mixture was stirred at r.t. for 2 h. The reaction was then
quenched with sat. aq. NaHCO3 (20 ml). The aq. layer was extracted with CH2Cl2 (30 ml), and the
combined org. layers were dried (Na2SO4) and concentrated. The residue was purified by CC to furnish
18 (2.18 g, 92%). [a]2D7 ¼ þ2.9 (c ¼ 0.5, CHCl3). IR: 3449, 2929, 2855, 1246, 1105, 768, 702. 1H-NMR
(200 MHz, CDCl3): 7.72 – 7.63 (m, 4 H); 7.44 – 7.21 (m, 8 H); 6.89 (d, J ¼ 8.0, 2 H); 4.54 – 4.42 (m, 2 H);
4.14 – 3.98 (m, 2 H); 3.82 (s, 3 H); 3.71 (m, 1 H); 3.51 – 3.44 (m, 2 H); 1.81 – 1.70 (m, 2 H); 1.38 (s, 3 H);
1.22 (s, 3 H); 1.08 (d, J ¼ 8.0, 3 H); 1.05 (s, 9 H). 13C-NMR (50 MHz, CDCl3): 136.0; 129.5; 129.3; 129.0;
127.6; 127.2; 113.8; 108.3; 80.4; 75.8; 73.3; 70.4; 67.5; 55.2; 43.5; 27.6; 24.7; 23.0; 19.2. ESI-MS: 571 ([M þ
Na]þ). Anal. calc. for C33H44O5Si (548.78): C 72.22, H 8.08; found: C 72.19, H 8.05.
5-O-[(tert-Butyl)(diphenyl)silyl]-4,6-dideoxy-2,3-O-(1-methylethylidene)-d-xylo-hexitol (19). Com-
pound 19 was prepared as described for 15. Yield: 1.31 g (84%). [a]2D7 ¼ ꢁ6.2 (c ¼ 1.0, CHCl3). IR: 3448,
1
2932, 2858, 1107, 703. H-NMR (200 MHz, CDCl3): 7.86 – 7.63 (m, 4 H); 7.46 – 7.38 (m, 6 H); 4.10 (m,
1 H); 3.82 (m, 1 H); 3.72 (m, 1 H); 3.58 (m, 1 H); 1.71 – 1.52 (m, 2 H); 1.38 (s, 3 H); 1.30 (s, 3 H); 1.09 (d,
J ¼ 7.0, 3 H); 1.02 (s, 9 H). 13C-NMR (50 MHz, CDCl3): 136.2; 134.9; 129.9; 127.8; 108.8; 81.9; 73.8; 67.2;
61.6; 42.9; 27.1; 24.3; 22.5; 19.1. ESI-MS: 451 ([M þ Na]þ). Anal. calc. for C25H36O4Si (428.64): C 70.05, H
8.47; found: C 70.03, H 8.41.
5-O-[(tert-Butyl)(diphenyl)silyl]-4,6-dideoxy-2,3-O-(1-methylethylidene)-1-O-[(4-methylphenyl)-
sulfonyl]-d-xylo-hexitol (20). To a stirred soln. of 19 (1.2 g, 2.80 mmol) in CH2Cl2 (15 ml), Et3N (0.58 ml,
4.20 mmol) and DMAP (34 mg, 0.28 mmol) were added at r.t., and the mixture was stirred for 10 min.
TsCl (639 mg, 3.36 mmol) was then added, and stirring was continued at r.t. for 3 h. The reaction was
quenched with sat. aq. NH4Cl (3 ml), and the mixture was extracted with CH2Cl2 (30 ml). The combined
org. layers were washed with H2O (10 ml) and brine (5 ml), then dried (Na2SO4), and concentrated. The
residue was purified by CC to obtain 20 (1.45 g, 89%). [a]2D7 ¼ ꢁ6.5 (c ¼ 0.4, CHCl3). IR: 3449, 2928,
1
2856, 1369, 1178, 1106, 770, 703. H-NMR (200 MHz, CDCl3): 7.84 – 7.62 (m, 6 H); 7.48 – 7.30 (m, 8 H);
4.11 – 3.95 (m, 4 H); 3.67 (m, 1 H); 2.45 (s, 3 H); 1.61 – 1.50 (m, 2 H); 1.28 (s, 3 H); 1.22 (s, 3 H); 1.07 (d,
J ¼ 7.0, 3 H); 1.02 (s, 9 H). 13C-NMR (50 MHz, CDCl3): 145.2; 136.4; 135.0; 133.2; 129.4; 129.1; 128.0;
127.8; 127.7; 109.9; 78.5; 74.1; 43.9; 29.6; 27.0; 24.2; 22.8; 18.9. ESI-MS: 605 ([M þ Na]þ). Anal. calc. for
C32H42O6SSi (582.82): C 65.94, H 7.26; found: C 65.89, H 7.22.
4,6-Dideoxy-2,3-O-(1-methylethylidene)-1-O-[(4-methylphenyl)sulfonyl]-d-xylo-hexitol (5). To a
stirred soln. of 20 (1.0 g, 1.71 mmol) in dry THF (10 ml), 1m soln. of Bu4NF (5.15 ml, 5.15 mmol) in
THF was added at 08, and the mixture was stirred for 2 h at r.t. The reaction was quenched with sat. aq.
NH4Cl (15 ml), and the mixture was extracted with CH2Cl2 (30 ml). The combined org. layers were
washed with H2O (10 ml) and brine (5 ml), dried (Na2SO4), and concentrated. The residue was purified
by CC to obtain 5 (0.5 g, 85%). [a]2D7 ¼ þ2.0 (c ¼ 0.2, CHCl3). IR: 3443, 2926, 1456, 1178, 780. 1H-NMR
(200 MHz, CDCl3): 7.80 (d, J ¼ 8.0, 2 H); 7.38 (d, J ¼ 8.0, 2 H); 4.18 – 4.03 (m, 4 H); 4.00 (m, 1 H); 3.85

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Helvetica Chimica Acta – Vol. 97 (2014)
(m, 1 H); 2.42 (s, 3 H); 1.74 – 1.62 (m, 2 H); 1.39 (s, 3 H); 1.32 (s, 3 H); 1.23 (d, J ¼ 7.0, 3 H). 13C-NMR
(50 MHz, CDCl3): 143.3; 130.7; 128.1; 126.0; 107.6; 76.5; 73.6; 67.2; 63.3; 39.2; 25.2; 24.4; 22.1; 21.6; 19.9.
ESI-MS: 367 ([M þ Na]þ). Anal. calc. for C16H24O6S (344.42): C 55.80, H 7.02; found: C 55.78, H 7.0.
Ophiocerin C (¼1,5-Anhydro-4,6-dideoxy-d-xylo-hexitol; 3). To a soln. of 5 (100 mg, 0.3 mmol) in
dry Et2O (2 ml) was added to a stirred suspension of tBuOK (71.6 mg, 0.63 mmol) in dry Et2O (5 ml) at
08, and the mixture was stirred for 2 h at 08. The reaction was quenched with sat. aq. NH4Cl (5 ml), and
the mixture was extracted with Et2O (10 ml). The combined org. layers were washed with H2O and brine
and then treated with TsOH (10 mg) and MeOH (5 ml) with stirring at r.t. for 2 h. The reaction was
quenched with sat. aq. NaHCO3 soln., and the solvents (MeOH and Et2O) were evaporated under
reduced pressure. The residue was extracted with CH2Cl2 (2 ꢂ 20 ml), and the combined org. layers were
washed with H2O and brine, then dried (Na2SO4), and concentrated. The residue was purified by CC to
obtain 3 (30 mg, 79% over two steps). White solid. M.p. 82 – 838. Spectroscopic data: see [3f].
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Received March 11, 2014