Stereoselective total synthesis of crassalactone A, a natural cytotoxic styryl lactone

Article abstract of DOI:10.1002/hlca.201400237

A stereoselective total synthesis of a naturally occurring cytotoxic styryl lactone, crassalactone A (1), has been accomplished. The synthesis involves (-)-diisopropyl D-tartrate as the starting material, and the stereoselective additions of Grignard reag

Full text of DOI:10.1002/hlca.201400237

Helvetica Chimica Acta – Vol. 98 (2015)
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Stereoselective Total Synthesis of Crassalactone A, a Natural Cytotoxic Styryl
Lactone1)
by Parigi Raghavendar Reddy and Biswanath Das*
Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad-
500 007, India (phone: þ 91-40-7193434; fax: þ 91-40-7160512; e-mail: biswanathdas@yahoo.com)
A stereoselective total synthesis of a naturally occurring cytotoxic styryl lactone, crassalactone A (1),
has been accomplished. The synthesis involves (À)-diisopropyl d-tartrate as the starting material, and the
stereoselective additions of Grignard reagent and MeNO2 to two chiral aldehyde intermediates as the
key steps.
Introduction. – Polyanthia species are well-known for their valuable constituents
with cytotoxic, anti-HIV, antimicrobial, and antimalarial properties [1]. From the
cytotoxic AcOEt extract of the leaves and twigs of the plant Polyanthia crassa, a styryl
lactone, crassalactone A (1; Fig.), together with several other constituents, have been
isolated [2]. The structure of 1 was established on the basis of spectroscopic data, and
the absolute configuration by chemical conversions. The cytotoxic effect of 1 was
tested, and the compound was found to exhibit broad cytotoxic activity against a panel
of mammalian and rat cancer cell lines. Due to fascinating structural features and the
impressive bioactivity of 1, we were interested in its total synthesis. Earlier two
syntheses of this compound have been reported [3]. In the first synthesis, (R)-mandelic
acid was used as the starting material, and OsO4 (which is poisonous and volatile) was
employed for cis-hydroxylation [3a]. In the second synthesis, 1,5-d-gluconolactone was
the starting material, and the overall synthetic time (95 h) was longer [3b]. Herein, we
disclose an alternative stereoselective synthesis of 1 without applying OsO4 (used in the
first synthesis) and maintaining the synthetic time shorter (59 h) (compared to the
second synthesis). We have utilized a different starting material, (À)-diisopropyl d-
tartrate, and a different reaction sequence. However, the last step, the lactonization,
was analogous to that in the earlier second synthesis [3b].
Figure. Structure of crassalactone A
1
)
Part 83 of the series, ꢁSynthetic Studies on Natural Productsꢂ.
ꢀ 2015 Verlag Helvetica Chimica Acta AG, Zürich

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Results and Discussion. – In continuation of our works on the stereoselective
construction of natural products [4], we have realized that crassalactone A (1) can be
synthesized from the protected tetrahydroxy compound 2 (Scheme 1), which can be
derived from the commercially available (À)-diisopropyl d-tartrate (3).
Our synthesis (Scheme 2) was initiated by protection of two OH groups of 3 by
treatment with 2,2-dimethoxypropane (DMP) in toluene in the presence of TsOH to
Scheme 1. Retrosynthetic Analysis of 1
Scheme 2. Synthesis of 1
a) 2,2-Dimethoxypropane (DMP), TsOH, toluene, r.t. to reflux, overnight; 92%. b) LiAlH4, dry THF, 08
to r.t., 4 h; 88%. c) (tBu)Me2SiCl (TBSCl), 1H-imidazole, CH2Cl2, 3 h; 93%. d) 1) 2-Iodoxybenzoic acid
(IBX), DMSO, CH2Cl2, 08 to r.t., 2 h; 94%. 2) PhMgBr, THF, 6 h; 70%. e) TBSCl, 1H-imidazole,
CH2Cl2, 4 h; 96%. f) Pyridine hydrofluoride (Py · HF), THF, 08, 2 h; 82%. g) 1) IBX, DMSO, CH2Cl2, 08
to r.t., 2 h; 92%. 2) MeNO2, K2CO3 (aq.), THF, r.t., overnight; 88%. h) Diethyl azodicarboxylate
(DEAD), Ph3P, THF, 08 – reflux, 5 h; 79%. i) 1) K2CO3, KMnO4 (aq.), MgSO4, 08, 1 h. 2)
(F3CCH2O)2P(O)CH2CO2Me, NaH, dry THF, À 788, 1 h; 68% (over two steps). j) 3% MeOH/HCl, 08
to r.t., 5 h; 63%.

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form the acetonide derivative 4 (Scheme 2). The two ester groups of 4 were reduced
with LiAlH4 to furnish the diol 5. One of the OH groups of 5 was protected as the TBS
ether 6 by reaction with (tBu)Me2SiCl (TBSCl) and 1H-imidazole in CH2Cl2. The free
OH group of 6 was oxidized with 2-iodoxybenzoic acid (IBX), and the corresponding
aldehyde was treated with PhMgBr to afford compound 7 (dr 95 :5). The high
selectivity of the reaction was a result of 1,2-chelation control [5]. The major
diastereoisomer was separated, and its OH group was protected as the TBS ether to
yield compound 8, which, on treatment with pyridine hydrofluoride (Py · HF), resulted
in the selective removal of the TBS group of the primary OH moiety to afford the
alcohol 9 [6]. The latter was oxidized with IBX, and the generated aldehyde was
reacted with MeNO2 to give the nitro compound 10 (dr 96 :4). The conversion was
performed in good yield and high anti-selectivity, following the reaction conditions
reported earlier [7]. The major diastereoisomer was treated with cinnamic acid under
Mitsunobu esterification conditions [8] to form the ester 2 with inversion of the
configuration of the newly generated stereogenic center in 10. The nitro alkane moiety
of 2 was oxidized with alkaline KMnO4 [7] to the corresponding aldehyde, which was
utilized for Wittig olefination with (F3CCH2O)2P(O)CH2COOMe to furnish the (Z)-
olefin 11 [9]. The structure and configuration of 11 were clearly established by its NMR
spectra. Finally, the treatment of 11 with 3% MeOH/HCl resulted in the deprotection
of both the TBS and acetonide groups, and the simultaneous cyclization, forming a
lactone ring, afforded the target molecule 1. The physical (optical rotation) and
spectroscopic (1H- and 13C-NMR, and MS) properties of 1 were identical to those
reported for the naturally occurring crassalactone A [2].
In conclusion, we have developed a simple and straightforward synthesis of
crassalactone A (1), a natural cytotoxic styryl lactone, by using (À)-diisopropyl d-
tartrate as the starting material. The stereoslective additions of a Grignard reagent and
MeNO2 to two chiral aldehyde intermediates are the key steps involved in the present
synthesis.
The authors thank CSIR and UGC, New Delhi, for financial support.
Experimental Part
General. The solvents used were all of AR-grade. TLC: Merck silica gel 60 F254 plates. Column
chromatography (CC): silica gel (SiO2, 60 – 120 mesh; Qingdao Marine Chemical, P. R. China). Optical
rotations: JASCO DIP 360 digital polarimeter. NMR Spectra: Gemini 500-MHz spectrometer; in CDCl3;
d in ppm rel. to Me4Si as internal standard, J in Hz. ESI-MS: VG-Autospec micromass instrument; in m/z.
Bis(1-methylethyl) (4S,5S)-2,2-Dimethyl-1,3-dioxolane-4,5-dicarboxylate (4). To a soln. of 3 (1.0 g,
4.27 mmol) and 2,2-dimethoxypropane (DMP; 0.627 ml, 5.12 mmol) in toluene (10 ml), TsOH (0.73 g,
4.27 mmol) was added, and the mixture was heated at reflux for overnight. The mixture was cooled and
K2CO3 was added, excess K2CO3 was removed by filtration. The solvent was removed under reduced
pressure to afford crude product. Purification of the latter by CC afforded pure 4 (1.07 g, 92%). White
1
solid. [a]2D2 ¼ þ39.6 (c ¼ 1.0, CHCl3). H-NMR (500 MHz, CDCl3): 5.16 – 5.10 (m, 2 H); 4.70 (s, 2 H);
1.50 (s, 6 H); 1.31 (d, J ¼ 7.0, 12 H). 13C-NMR (125 MHz, CDCl3): 169.2; 113.8; 77.3; 69.8; 26.2; 21.9. ESI-
MS: 275 ([M þ H]þ). Anal. calc. for C13H22O6 (274.32): C 56.92, H 8.08; found: C 56.81, H 8.04.
[(4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl]dimethanol (5). To LiAlH4 (0.416 g, 10.94 mmol) at
08, dry THF (10 ml) was added slowly, and then a soln. of 4 (1.0 g, 3.64 mmol) in dry THF (5 ml) was
added dropwise at 08 under N2. The mixture was stirred at r.t. for 4 h. After completion of the reaction

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(TLC), the mixture was cooled to 08, the reaction was quenched with aq. Na2SO4 paste, and the mixture
was allowed to stir at r.t. Then, it was filtered through a pad of Celite, and washed with hot AcOEt
(20 ml). The filtrate was washed with brine (2 Â 10 ml), dried (Na2SO4), and evaporated under reduced
pressure. The crude product, on purification by CC, afforded pure 5 (0.520 g, 88%). Viscous yellow oil.
1
[a]2D2 ¼ À2.4 (c ¼ 1.4, CHCl3). H-NMR (500 MHz, CDCl3): 4.04 – 3.97 (m, 2 H); 3.81 – 3.64 (m, 4 H);
1.42 (s, 6 H); 13C-NMR (125 MHz, CDCl3): 109.4; 78.3; 62.2; 27.0. ESI-MS: 163 ([M þ H]þ). Anal. calc.
for C7H14O4 (162.08): C 51.84, H 8.70; found: C 51.72, H 8.75.
[(4R,5R)-5-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol (6).
To a soln. of 5 (0.500 g, 3.08 mmol) in 10 ml of dry CH2Cl2, 1H-imidazole (0.209 g, 3.08 mmol) and
TBSCl (0.466 g, 3.08 mmol) were added sequentially at 08. After stirring for 5 min, 4-(dimethylamino)-
pyridine (DMAP; cat. amount) was added to the mixture, and stirring was continued for 3 h at r.t. After
completion of the reaction (TLC), the mixture was extracted with CH2Cl2 (2 Â 5 ml). The combined org.
extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo. The crude product, on
purification by CC, afforded pure 6 (0.792 g, 93%). Yellowish oil. [a]2D2 ¼ À15.6 (c ¼ 1.5, CHCl3).
1H-NMR (500 MHz, CDCl3): 4.02 – 3.94 (m, 1 H); 3.99 – 3.85 (m, 2 H); 3.78 – 3.71 (m, 2 H); 3.67 (dd, J ¼
12.0, 10.0, 1 H); 2.45 (br. s, 1 H); 1.42 (s, 3 H); 1.40 (s, 3 H); 0.89 (s, 9 H); 0.09 (s, 6 H). 13C-NMR
(125 MHz, CDCl3): 109.2; 80.2; 78.1; 63.8; 62.8; 27.0; 26.9; 26.0; 18.4; À 5.3. ESI-MS: 277 ([M þ H]þ).
Anal. calc. for C13H28O4Si (276.45): C 56.48, H 10.21; found: C 56.37, H 10.17.
(R)-[(4R,5R)-5-({(tert-Butyl)(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-yl](phenyl)-
methanol (7). To an ice-cold soln. of 2-iodoxybenzoic acid (IBX; 1.52 g, 5.43 mmol) in DMSO (3 ml) was
added a soln. of 6 (0.750 g, 2.71 mmol) in dry CH2Cl2, and the mixture was stirred at r.t. for 2 h. The
reaction was quenched with sat. NaHCO3 soln. The mixture was diluted with CH2Cl2 (5 ml), filtered
through a Celite pad, and the pad was washed with CH2Cl2. The combined filtrates were washed with H2O
(10 ml), dried (Na2SO4), and the residue was concentrated under reduced pressure to afford the
aldehyde (0.699 g, 94%), which was used directly after flash chromatography for the next reaction.
The above aldehyde in dry THF (10 ml) was added slowly over 30 min to a stirred soln. of in situ
prepared PhMgBr (2.89 ml, 2.89 mmol) in THF at 08 under N2 and stirred at the same temp. After
completion of the reaction (TLC), the reaction was quenched with aq. NH4Cl, and then the mixture was
extracted with CH2Cl2 (2 Â 10 ml). The combined org. extracts were washed with brine, dried (Na2SO4),
and concentrated in vacuo. The crude product, on purification by CC, afforded pure 7 (0.597 g, 70%).
Viscous gel. [a]2D2 ¼ þ1.8 (c ¼ 1.5, CHCl3). 1H-NMR (500 MHz, CDCl3): 7.51 – 7.40 (m, 5 H); 4.82 (br. d,
J ¼ 7.0, 1 H); 4.29 (dd, J ¼ 9.0, 7.0, 1 H); 4.01 – 3.98 (m, 1 H); 3.52 (dd, J ¼ 12.0, 6.0, 1 H); 3.34 (dd, J ¼
12.0, 5.0, 1 H); 3.19 (br. s, 1 H); 1.52 (s, 6 H); 0.97 (s, 9 H); 0.10 (s, 3 H); 0.07 (s, 3 H). 13C-NMR
(125 MHz, CDCl3): 140.0; 128.9; 128.8; 127.0; 109.9; 81.5; 78.1; 74.9; 63.1; 27.4; 27.3; 25.9; 19.2; À 5.4.
ESI-MS: 353 ([M þ H]þ). Anal. calc. for C19H32O4Si (352.55): C 64.73, H 9.15; found: C 64.88, H 9.11.
(tert-Butyl)[(R)-[(4S,5R)-5-({[(tert-butyl)(dimethyl)silyl]oxy}methyl)-2,2-dimethyl-1,3-dioxolan-4-
yl](phenyl)methoxy]dimethylsilane (8). To a soln. of 7 (0.600 g, 1.69 mmol) in 10 ml of dry CH2Cl2, 1H-
imidazole (0.138 g, 2.03 mmol) and TBSCl (0.307 g, 2.03 mmol) were added sequentially at 08. After
stirring for 5 min, DMAP (cat. amount) was added to the mixture, and stirring was continued for 4 h at
r.t. After completion of the reaction (TLC), the mixture was extracted with CH2Cl2 (2 Â 10 ml). The
combined org. extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo. The crude
product, on purification by CC, afforded pure 8 (0.762 g, 96%). Oil. [a]2D2 ¼ þ2.2 (c ¼ 2.5, CHCl3).
1H-NMR (500 MHz, CDCl3): 7.41 – 7.31 (m, 5 H); 4.88 (d, J ¼ 7.0, 1 H); 4.12 (dd, J ¼ 9.0, 7.0, 1 H); 3.88 –
3.92 (m, 1 H); 3.61(dd, J ¼ 12.0, 5.0, 1 H); 3.40 (dd, J ¼ 12.0, 6.0, 1 H); 1.45 (s, 3 H); 1.31 (s, 3 H); 0.96 (s,
9 H); 0.95 (s, 9 H); 0.11 (s, 6 H); 0.08 (s, 6 H). 13C-NMR (125 MHz, CDCl3): 140.9; 128.1; 128.0; 127.9;
109.1; 81.0; 78.1; 75.8; 64.0; 27.6; 26.1; 18.2; À 4.8. ESI-MS: 467 ([M þ H]þ). Anal. calc. for C25H46O4Si2
(466.81): C 64.32, H 9.93; found: C 64.48, H 9.90.
{(4R,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}-
methanol (9). To a soln. of 8 (0.700 g, 1.49 mmol) in dry THF was added Py · HF (0.008 ml, 0.449 mmol)
at 08, and the mixture was stirred at the same temp. for 2 h. Reaction was monitored frequently, and, after
completion, it was quenched with sat. NaHCO3. The mixture was extracted with AcOEt, and combined
org. extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo. The crude product, on
purification by CC, afforded pure 9 (0.433 g, 82%). Oil. [a]2D2 ¼ À19.2 (c ¼ 1.5, CHCl3). 1H-NMR

Helvetica Chimica Acta – Vol. 98 (2015)
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(500 MHz, CDCl3): 7.42 – 7.33 (m, 5 H); 4.88 (d, J ¼ 7.0, 1 H); 4.13 (dd, J ¼ 9.0, 7.0, 1 H); 3.94 – 3.90 (m,
1 H); 3.62 (dd, J ¼ 12.0, 4.0, 1 H); 3.40 ((dd, J ¼ 12.0, 6.0, 1 H); 1.47 (s, 3 H); 1.30 (s, 3 H); 0.94 (s, 9 H);
0.08 (s, 3 H); 0.05 (s, 3 H). 13C-NMR (125 MHz, CDCl3): 140.9; 128.0; 127.9; 127.8; 109.0; 80.9; 78.0; 75.6;
63.8; 27.8; 26.0; 18.2; À 4.9. ESI-MS: 353 ([M þ H]þ). Anal. calc. for C19H32O4Si (352.55): C 64.73, H
9.15; found: C 64.64, H 9.19.
(1R)-1-{(4R,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-1,3-dioxo-
lan-4-yl}-2-nitroethanol (10). To an ice-cold soln. of IBX (0.634 g, 2.26 mmol) in DMSO (2 ml), was
added a soln. of 9 (0.400 g, 1.13 mmol) in 4 ml of dry CH2Cl2, and the mixture was stirred at r.t. for 2 h.
Then, the reaction was quenched with sat. NaHCO3 soln., and the mixture was diluted with CH2Cl2
(5 ml), filtered through a Celite pad, and the pad was washed with CH2Cl2. The combined filtrates were
washed with H2O (5 ml), dried (Na2SO4), and the residue was concentrated under reduced pressure to
afford the aldehyde (0.365 g, 92%), which was used directly after flash chromatography for the next
reaction.
To a stirred soln. of the above aldehyde and MeNO2 (0.14 ml, 2.70 mmol) in THF (5 ml) was added
aq. K2CO3 (0.193 g, 1.40 mmol) at r.t. The mixture was stirred overnight at r.t. and then treated with H2O.
The mixture was extracted with AcOEt, and the combined org. extracts were washed with brine, dried
(Na2SO4), and concentrated in vacuo. The crude product, on purification by CC, afforded pure 10
(0.377 g, 88%). Pale-yellow liquid. [a]D22 ¼ À9.9 (c ¼ 1.0, CHCl3). 1H-NMR (500 MHz, CDCl3): 7.40 – 7.32
(m, 5 H); 5.15 (d, J ¼ 7.0, 1 H); 4.61 (br. d, J ¼ 12.0, 1 H); 4.48 – 4.40 (m, 2 H); 4.32 (br. t, J ¼ 6.0, 1 H);
4.10 (dd, J ¼ 12.0, 6.0, 1 H); 3.55 (dd, J ¼ 12.0, 10.0, 1 H); 1.40 (s, 3 H); 1.29 (s, 3 H); 0.92 (s, 9 H); 0.11 (s,
3 H); 0.04 (s, 3 H). 13C-NMR (125 MHz, CDCl3): 138.0; 128.0; 127.9; 127.8; 109.9; 83.8; 78.9; 76.1; 73.9;
70.3; 26.2; 25.9; 18.2; À 5.1. ESI-MS: 412 ([M þ H]þ). Anal. calc. for C20H33NO6Si (411.57): C 58.37, H
8.08; found: C 58.45, H 8.03.
(1S)-1-{(4R,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-1,3-dioxo-
lan-4-yl}-2-nitroethyl (2E)-3-Phenylprop-2-enoate (2). To a soln. of 10 (0.300 g, 0.728 mmol), cinnamic
acid (0.140 g, 0.946 mmol), and Ph3P (0.381 g, 1.45 mmol) in dry THF (5 ml) was added DEAD (0.20 ml,
1.31 mmol) dropwise during 5 min. The soln. was stirred at 08 for 1 h, and then at reflux for 4 h. After
completion (TLC), the reaction was quenched with sat. NaHCO3, and the reaction was extracted with
AcOEt (2 Â 10 ml). The combined extracts were dried and concentrated in vacuo. The crude product, on
purification by CC, afforded pure 2 (0.311 g, 79%). Pale-yellow liquid. [a]2D2 ¼ þ20.7 (c ¼ 1.5, CHCl3).
1H-NMR (500 MHz, CDCl3): 7.40 – 7.35 (m, 10 H); 7.34 (d, J ¼ 16.0, 1 H); 6.95 (d, J ¼ 16.0, 1 H); 5.39 –
5.35 (m, 1 H); 4.97 (d, J ¼ 7.0, 1 H); 4.37 – 4.31 (m, 2 H); 4.01 (dd, J ¼ 12.0, 8.0, 2 H); 1.28 (s, 6 H); 0.92 (s,
9 H); 0.10 (s, 3 H); 0.01 (s, 3 H). 13C-NMR (125 MHz, CDCl3): 163.9; 144.1; 139.0; 128.5; 128.4; 128.3;
127.1; 127.0; 115.9; 110.5; 84.1; 78.2; 74.9; 73.2; 68.8; 29.9; 25.9; 18.2; À 5.0. ESI-MS: 542 ([M þ H]þ).
Anal. calc. for C29H39NO7Si (541.72): C 64.30, H, 7.26; found: C 64.39, H 7.22.
Ethyl (2Z,4S)-4-{(4R,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-
1,3-dioxolan-4-yl}-4-{[(2E)-3-phenylprop-2-enoyl]oxy}but-2-enoate (11). To the soln. of 2 (0.250 g,
0.461 mmol) in MeOH (3 ml) cooled to 08 was added dropwise a freshly prepared MeOH soln. of K2CO3
(0.095 g, 0.691 mmol) under inert atmosphere. After stirring for 1 h, a freshly prepared aq. KMnO4
(0.051 g, 0.322 mmol) and MgSO4 (0.041 g, 0.345 mmol) were added dropwise, maintaining the temp. at
08. The entire mixture was stirred for 1 h at the same temp. and filtered through a pad of silica gel,
followed by washing with AcOEt. The combined org. extracts were washed with brine, dried (Na2SO4),
and concentrated in vacuo. This residue was used as such for the next step without further purification.
To NaH (0.011 g, 0.422 mmol), 2 ml of dry THF was added at 08, under N2. After 5 min, bis(2,2,2-
trifluoromethyl) [(methoxycarbonyl)methyl]phosphonate (0.161 g, 0.507 mmol) in 2 ml of dry THF was
added dropwise at 08, and the mixture was stirred for 30 min. The mixture was cooled to À 788, and the
above aldehyde in dry THF (3 ml) was added dropwise, and the resulting mixture was stirred for 1 h at
the same temp. After completion (TLC), the reaction was quenched with sat. NH4Cl (2 ml), and the
product was extracted with AcOEt (2 Â 5 ml), dried (Na2SO4), and evaporated in vacuo, and the crude
product, on purification by CC, afforded pure 11 (0.182 g, 68%). Yellow liquid. [a]2D2 ¼ þ16 (c ¼ 0.9,
CHCl3). 1H-NMR (500 MHz, CDCl3): 7.75 (d, J ¼ 16.0, 1 H); 7.54 – 7.28 (m, 10 H); 6.53 (d, J ¼ 16.0, 1 H);
6.22 (dd, J ¼ 10.0, 2.0, 1 H); 6.01 (d, J ¼ 10.0, 1 H); 5.01 (dd, J ¼ 2.5, 2.0, 1 H); 4.85 (d, J ¼ 2.5, 1 H); 4.46 –
4.41 (m, 1 H); 4.32 – 4.21 (m, 2 H); 4.18 – 4.13 (m, 1 H); 1.62 – 1.49 (m, 9 H); 1.10 (s, 9 H); 0.27 (s, 3 H);

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Helvetica Chimica Acta – Vol. 98 (2015)
0.20 (s, 3 H). 13C-NMR (125 MHz, CDCl3): 165.1; 164.2; 149.7; 145.0; 140.1; 134.9; 130.1; 129.0; 128.8;
128.6; 125.2; 121.0; 117.8; 110.1; 75.2; 74.8; 70.2; 65.7; 61.2; 29.8; 25.6; 18.4; 16.6; À 4.6; À 4.5. ESI-MS:
581 ([M þ H]þ). Anal. calc. for C33H44O7Si (580.79): C 68.24, H 7.64; found: C 68.39, H 7.68.
(2S,3S)-2-[(1R,2R)-1,2-Dihydroxy-2-phenylethyl]-6-oxo-3,6-dihydro-2H-pyran-3-yl (2E)-3-Phenyl-
prop-2-enoate (1). To compound 11 (150 mg, 0.258 mmol) at 08 was added 3% HCl in MeOH (2 ml), and
the mixture was stirred at r.t. for 5 h. After completion of the reaction (TLC), the mixture was diluted
with AcOEt and washed with H2O and brine, dried (Na2SO4), and concentrated in vacuo to give crude
product. The crude product, on purification by CC, afforded pure crassalactone A (1; 61 mg, 63%). White
solid. [a]2D2 ¼ þ320 (c ¼ 1.5, CHCl3). 1H-NMR (500 MHz, CDCl3): 7.63 (d, J ¼ 16.0, 1 H); 7.51 – 7.28 (m,
10 H); 7.01 (dd, J ¼ 10.0, 6.0, 1 H); 6.35 (d, J ¼ 16.0, 1 H); 6.20 (d, J ¼ 10.0, 1 H); 5.28 (dd, J ¼ 6.0, 2.5,
1 H); 4.90 (d, J ¼ 6.0, 1 H); 4.75 (dd, J ¼ 6.0, 2.5, 1 H); 4.25 (m, 1 H); 2.00 (br. s, 2 H). 13C-NMR
(125 MHz, CDCl3): 165.6; 162.4; 146.5; 140.5; 139.8; 133.5; 130.8; 128.8; 128.6; 128.3; 128.2; 126.4; 123.8;
116.4; 77.5; 73.5; 73.2; 62.6. ESI-MS: 381 ([M þ H]þ). Anal. calc. for C22H20O6 (380.40): C 69.46, H 5.30;
found: C 69.34, H 5.35.
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Received July 15, 2014