Stereoselective Total Synthesis of Mangiferaelactone using D -Mannose as a Chiral Pool

Article abstract of DOI:10.1002/hlca.201500103

A convergent total synthesis of mangiferaelactone has been accomplished in a highly stereoselective manner from readily available D-mannose. The following methods like organocatalytic enantioselective epoxidation, ring-closing metathesis, and Steglich est

Full text of DOI:10.1002/hlca.201500103

Helvetica Chimica Acta – Vol. 98 (2015)
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Stereoselective Total Synthesis of Mangiferaelactone using d-Mannose as a
Chiral Pool
by Basi V. Subba Reddy*, Pathuri Sivaramakrishna Reddy, Kummari Vijaya Babu,
Bhemavarapu Phaneendra Reddy, and Jhillu Singh Yadav
Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India
(fax: þ 914027160512; e-mail: basireddy@iict.res.in)
A convergent total synthesis of mangiferaelactone has been accomplished in a highly stereoselective
manner from readily available d-mannose. The following methods like organocatalytic enantioselective
epoxidation, ring-closing metathesis, and Steglich esterification have been employed as key steps, which
make this approach more attractive.
Introduction. – The polyketide natural products were isolated from fungal sources
and are known to possess potent biological activities such as antibacterial, antifungal,
cytotoxic, and phytotoxic behavior, which make them attractive synthetic targets. In
particular, 10-membered macrolides such as cytospolides [1], decarestrictines [2][3],
seimatopolides [3], and stagonolides [4] have received significant attention due to their
interesting biological properties.
Mangiferaelactone (1) (Fig.), a 10-membered macrolide, was isolated from the
solid culture of the endophytic fungus, Pestatotriopsis mangiferae. The structure of 1
was established by 1D- and 2D-NMR spectroscopy, and the absolute configuration
was determined by vibrational circular dichroism (VCD). The minimum inhibitory
concentration (MIC) of mangiferaelactone against Listeria monocytogenes and
Bacillus cereus was 1.68 mg/ml and 0.55 mg/ml, respectively [5]. Due to inherent
biological properties, mangiferaelactone has become an important synthetic target for
medicinal chemistry, and to date, only two approaches have been reported for its
synthesis [6].
As part of our interest in the total synthesis of biologically active natural products
[7], we herein report a novel strategy for the synthesis of mangiferaelactone (1)
employing d-mannose (2) as a cost-effective and readily available precursor.
Figure. Structure of mangiferaelactone
ꢀ 2015 Verlag Helvetica Chimica Acta AG, Zürich

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Results and Discussion. – Our retrosynthetic analysis of mangiferaelactone (1)
reveals that it could be synthesized through a ring-closing metathesis of 3 [6], which in
turn could be prepared by the esterification of acid 4 with alcohol 5. The intermediates
4 and 5 could easily be accessed from commercially available pentane-1,5-diol 6 and d-
mannose 2, respectively (Scheme 1).
Scheme 1. Retrosynthetic Analysis of Mangiferaelactone (1)
Accordingly, the synthesis of mangiferaelactone (1) began from d-mannose (2).
Treatment of 2 with I2 in dry acetone at room temperature over 24 h furnished the
corresponding diisopropylidene derivative, which was then subjected to a one-carbon
Wittig homologation with MePh3PþBr– in the presence of BuLi to give the alkenol 7 in
82% yield [8]. Protection of 7 as its tosylate 8 using TsCl and DABCO in CH2Cl2 [9],
followed by the selective hydrolysis of 8 using I2 in MeOH at 08 to 408 afforded the diol
in 75% yield [10]. The diol was then subjected to oxidative cleavage using NaIO4 to
generate an aldehyde [11], which was subsequently reduced with NaBH4 to provide the
alcohol 9 in 80% yield. The alcohol 9 was further treated with K2CO3 in MeOH to
furnish the epoxide 10 in 75% yield. Regioselective ring-opening of epoxide 10 with
Grignard reagent C6H13MgBr in the presence of a catalytic amount of copper cyanide
gave the corresponding alkenol 5 in quantitative yield [12] (Scheme 2).
Next, we focused on the synthesis of the other key intermediate 4, which was started
from pentane-1,5-diol 6. Mono-protection of the diol 6 with BnBr in the presence of
NaH in THF afforded the benzyl ether in 88% yield, which was then subjected to IBX
oxidation to give the aldehyde 11 in 87% yield. The crude aldehyde 11 was further
subjected to organo-catalyzed asymmetric epoxidation with catalyst A to give the
terminal epoxide 12 (90% ee; by HPLC analysis) in 86% yield [13]. Ring opening of 12
with trimethylsulfonium iodide in the presence of BuLi in THFat À 208 gave the allylic
alcohol in 88% yield [14], which was then protected as its TBS ether 13 using TBSCl

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Scheme 2. Synthesis of the Alcohol Fragment from d-Mannose
a) 1. I2, acetone, r.t., 24 h. 2. MePh3PþBr–, BuLi, THF, À 258 – r.t.; 82%. b) TsCl, DABCO, CH2Cl2, 15 h;
80%. c) 1. I2, MeOH, 408, 5 h; 75%. 2. NaIO4, THF/H2O 4 :1, r.t., 2 h. 3. NaBH4, MeOH, 0.5 h; 80%.
d) K2CO3, MeOH, 08 – r.t., 2 h; 75%. e) C6H13MgBr, CuCN, THF, À 408 – r.t., 1 h; 90%.
and imidazole. Compound 13 was further treated with Li/naphthalene to afford the
alcohol 14 in 90% yield. Oxidation of the alcohol 14 with TEMPO-BAIB followed by
Pinnick oxidation afforded the acid 4 in 82% yield (Scheme 3).
Finally, we attempted the coupling of alcohol 5 with carboxylic acid 4 so as to
construct a 10-membered ring via RCM reaction [6]. Under Steglich conditions (DCC/
DMAP), the coupling of alcohol 5 with acid 4 gave the corresponding ester 3 in 85%
yield [15]. Removal of the TBS ether using pyridine · HF followed by a ring-closing
metathesis of 3 using Grubbsꢁ second generation catalyst [16] in CH2Cl2 under reflux
conditions for 6 h gave the 10-membered macrolide 15 in 80% yield. Esterification of
Scheme 3. Synthesis of the Acid Fragment from Diol
a) 1. BnBr, NaH, THF, 08 – r.t., 6 h; 88%. 2. IBX, DMSO, CH2Cl2, 08 – r.t., 4 h; 87%. b) 50 mol-%
(CF3COO)2Cu · H2O, 20 mol-% cat. A, LiCl, Na2S2O8, MeCN, NaBH4, 08, 15 min, KOH, r.t., 30 min;
86% c) 1. Me3SI, BuLi, THF, À 208 – r.t., 10 h; 88%. 2. TBSCl, imidazole, CH2Cl2, 4 h; 85%. d) Li,
naphthalene, À 208, 70 min; 90%. e) 1. TEMPO-BAIB, CH2Cl2, 08 – r.t., 2 h. 2. NaClO2, NaH2PO4 · 2
H2O, 2-methylbut-2-ene, MeCN, 30 min; 82%.

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the macrolide 15 with succinic anhydride (75% yield) [17] followed by the removal of
acetonide using CeCl3 · 7 H2O under reflux conditions [18] furnished the desired
molecule, mangiferaelactone (1) in 73% yield. The spectroscopic data (1H- and
13C-NMR, IR, [a]2D5 ) of mangiferaelactone (1) were identical in all respects with the
data reported in the literature [6] (Scheme 4).
Scheme 4. Synthesis of Mangiferaelactone
a) DCC, DMAP, CH2Cl2, r.t., 6 h; 85%. b) 1. Pyridine · HF, THF, 08 – r.t., 8 h; 80%. 2. 5 mol-% Grubbsꢁ
catalyst-II, CH2Cl2, reflux, 6 h; 80%. c) C4H4O3, DMAP, CH2Cl2, r.t., 8 h; 75%. d) CeCl3 · 7 H2O, MeCN,
808, 5 h; 73%.
In summary, we have developed a concise and convergent approach for the total
synthesis of mangiferaelactone (1) in a highly stereoselective manner. Our approach
involves MacMillan asymmetric epoxidation, Steglich esterification, and ring-closing
metathesis as the key steps.
P. S. R. and B. P. R. thank CSIR, and K. V. B. thanks UGC New Delhi for the award of fellowship.
Experimental Part
General. All reagents were reagent grade and used without further purification unless specified
otherwise. Solvents were distilled prior to use: THF, toluene, and Et2O were distilled from Na and
benzophenone ketyl; MeOH from Mg and I2; CH2Cl2 from CaH2. All air- or moisture-sensitive reactions
were conducted under N2 or Ar in flame-dried or oven-dried glassware with magnetic stirring. Column
chromatography (CC): silica gel (SiO2, 60 – 120 mesh or 100 – 200 mesh) packed in glass columns.
Technical grade AcOEt and petroleum ether used for CC were distilled prior to use. Optical rotations:
JASCO DIP 300 digital polarimeter using a 1 ml cell with a 1 dm path length. IR Spectra: PerkinElmer
1
IR-683 spectrophotometer; KBr pellets and CHCl3; neat (as mentioned); n˜ in cmÀ1. H- and 13C-NMR
spectra: Varian Gemini FT-200, Bruker Avance 300, and Bruker Avance 500 spectrometers at 200, 300 or
500 MHz, in CDCl3 or C6D6; d in ppm rel. to Me4Si as internal standard, J in Hz. ESI-MS and HR-ESI-
MS: CEC-21-11013 or Finnigan Mat 1210 double-focusing mass spectrometers operating at a direct inlet
system or LC/MSD Trap SL (Agilent Technologies); in m/z.

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(R)-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl][(4S,5R)-5-ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]me-
thanol (7). For synthetic procedure and spectroscopic data, see [8].
(R)-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl][(4R,5R)-5-ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]-
methyl 4-Methylbenzenesulfonate (8). For synthetic procedure and spectroscopic data, see [9].
(1R)-1-[(4R,5R)-5-Ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethyl 4-Methylbenzenesulfo-
nate (9) [10][11]. To a stirred soln. of 8 (10 g, 24.27 mmol) in MeOH (80 ml) at 08, I2 was added, the
mixture was warmed to 408 and then stirred at the same temp. for 5 h. After completion of the reaction as
indicated by TLC, a sat. aq. Na2S2O3 soln. (50 ml), was added. The org. phase was separated, and the aq.
layer was extracted with AcOEt (3 Â 70 ml). Purification by CC over SiO2 provided the diol. Then, the
resulting diol was treated with NaIO4 in the mixture of THF/H2O 4 :1 at r.t. for 2 h. After completion of
the reaction as indicated by TLC, filtration of the mixture gave the crude aldehyde (5.6 g, 16.47 mmol).
This crude aldehyde was treated with NaBH4 (1.25 g, 32.94 mmol) in MeOH for 30 min, and the mixture
was concentrated in vacuo. Purification by CC over SiO2 provided the alcohol 9 (4.5 g, 80%) as a colorless
oil. Rf (AcOEt/hexane 1:4) 0.45. [a]2D5 ¼ þ34.6 (c ¼ 1.0, CHCl3). IR (KBr): 3234, 2928, 2848, 1545, 1452,
1363, 1258, 926, 768. 1H-NMR (300 MHz, CDCl3): 1.26 (s, 3 H); 1.35 (s, 3 H); 2.45 (s, 3 H); 3.82 – 3.95 (m,
2 H); 4.37 (t, J ¼ 6.5, 1 H); 4.62 – 4.68 (m, 2 H); 5.22 – 5.39 (m, 2 H); 5.76 – 5.84 (m, 1 H); 7.35 (d, J ¼ 8.0,
2 H); 7.80 (d, J ¼ 8.3, 2 H). 13C-NMR (75 MHz, CDCl3): 21.6; 29.6; 30.9; 61.7; 76.1; 82.9; 86.0; 117.7;
119.8; 127.8; 129.9; 130.1; 131.1; 137.0; 145.5. ESI-MS: 365 ([M þ Na]þ).
(4R,5R)-4-Ethenyl-2,2-dimethyl-5-[(2S)-oxiran-2-yl]-1,3-dioxolane (10) [19]. To a stirred soln. of 9
(4.5 g, 13.1 mmol) in MeOH (50 ml), K2CO3 (3.63 g, 26.2 mmol) was added slowly at 08portion wise. The
resulting mixture was stirred for 2 h at r.t. After completion of the reaction (monitored by TLC), the
mixture was diluted with MeOH (20 ml) and filtered through a small pad of Celite, evaporated in vacuo,
and concentrated under reduced pressure. The crude residue was purified by CC over SiO2 to give 10
(1.67 g, 75%) as colorless oil. Rf (AcOEt/hexane 1:5) 0.3. [a]2D5 ¼ þ54.31 (c ¼ 1.0, CHCl3). IR (KBr):
1
2958, 2856, 1566, 1361, 1253, 1096, 836, 775. H-NMR (300 MHz, CDCl3): 1.26 (s, 3 H); 1.40 (s, 3 H);
2.67 – 2.70 (m, 1 H); 2.84 (t, J ¼ 3.9, 1 H); 2.94 – 3.00 (m, 1 H); 3.77 (t, J ¼ 6.9, 1 H); 4.75 (t, J ¼ 6.6, 1 H);
5.33 – 5.53 (m, 2 H); 5.94 – 6.06 (m, 1 H).13C-NMR (75 MHz, CDCl3): 24.5; 25.6; 46.8; 56.8; 79.2; 82.0;
117.8; 119.8; 130.3. HR-ESI-MS: 193.2051 ([M þ Na]þ, C9H14NaO3þ ; calc. 193.2057).
(1S)-1-[(4S,5R)-5-Ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]octan-1-ol (5) [6a]. To a stirred soln. of
epoxide 10 (1.67 g, 9.8 mmol) and CuCN (120 mg, 0.98 mmol) in THF (50 ml) at À 408 was added
C6H13MgBr (Mg: 930 mg, 39.20 mmol, C6H13Br: 39.20 mmol); the resulting mixture was stirred at this
temp. for 30 min before being allowed to warm to r.t. over a period of 1 h. The reaction was quenched
with a sat. aq. NH4Cl soln. (30 ml). The org. phase was separated, and the aq. layer was extracted with
AcOEt (3 Â 50 ml). The combined org. phases were dried (Na2SO4), filtered, and concentrated in vacuo.
Purification by CC over SiO2 provided 5 (2.26 g, 90%) as light-yellow oil. Rf (AcOEt/hexane 1:4) 0.50.
For spectroscopic data, see [6].
(2R)-2-[3-(Benzyloxy)propyl]oxirane (12) [13]. To a stirred soln. of cat. A (20 mol-%, 1.39 g,
5.2 mmol), LiCl (3.28 g, 78.12 mmol), (CF3COO)2Cu · H2O (3.76 mg, 13.02 mmol), Na2S2O8 (6.19 g,
26.04 mmol) in MeCN (120 ml) and H2O (1.03 ml, 57.29 mmol) was added aldehyde 11 (5 g, 26.04 mmol)
at 208, and the mixture was stirred vigorously for 2 h at the same temp. The mixture was then cooled to 08,
before NaBH4 (2.51 g, 66.14 mmol) was added. After 10 min, the mixture was warmed to r.t., and then a
freshly prepared aq. soln. of KOH (40 ml) in EtOH (20 ml, 20 g KOH dissolved in 40 ml dist. H2O) was
added. The resulting mixture was stirred vigorously for 30 min. After completion, the reaction was
quenched with 50 ml of dist. H2O. The mixture was extracted with AcOEt (3 Â 50 ml), washed with brine
(1 Â 50 ml), dried (Na2SO4), filtered, and concentrated in vacuo maintaining the bath temp. at 308. The
resulting oil was purified by CC over SiO2 to afford the epoxide 12 (4.3 g, 86%) as a colorless oil. Rf
(AcOEt/hexane 1:4) 0.70. [a]2D5 ¼ þ16.50 (c ¼ 1.0, CHCl3). IR (KBr): 3033, 2860, 1603, 1495, 1258, 1100,
1
1013, 911. H-NMR (300 MHz, CDCl3): 1.55 – 1.84 (m, 4 H); 2.46 – 2.48 (m, 1 H); 2.74 (t, J ¼ 4.8, 1 H);
2.91 – 2.96 (m, 1 H); 3.48 – 3.56 (m, 2 H); 4.51 (s, 2 H); 7.25 – 7.36 (m, 5 H). 13C-NMR (75 MHz, CDCl3):
26.1; 29.2; 47.0; 52.0; 69.6; 72.8; 127.4; 127.5; 127.6; 128.3; 138.3. HR-ESI-MS: 215.1042 ([M þ Na]þ,
C12H16NaOþ2 ; calc. 215. 1040).
{[(3R)-6-(Benzyloxy)hex-1-en-3-yl]oxy}(tert-butyl)dimethylsilane (13) [14]. To a stirred soln. of
trimethylsulfonium iodide (13.7 g, 67.18 mmol) in dry THF (100 ml) was added BuLi in hexane (2.5m,

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26.8 ml, 67.18 mmol) at À 208, and the mixture was stirred at r.t. for 3 h. Then, the mixture was cooled to
À 208 again, and epoxide 12 (4.3 g, 22.39 mmol) in dry THF (40 ml) was slowly added drop wise, and the
mixture was stirred at r.t. for 10 h. After completion of the reaction, a sat. aq. NH4Cl soln. (50 ml) was
added. The org. phase was separated, and the aq. layer was extracted with AcOEt (3 Â 60 ml). The
combined org. phases were dried (Na2SO4), filtered, and concentrated in vacuo. Purification by CC over
SiO2 provided the alcohol (4.05 g, 88%). To a cooled soln. of the alcohol (4.05 g, 19.66 mmol) and 1H-
imidazole (2.67 g, 39.32 mmol) in dry CH2Cl2 (50 ml) was added TBSCl (3.25 g, 21.62 mmol), and the
mixture was stirred at r.t. for 4 h. After completion of the reaction (TLC), the mixture was diluted with
H2O (10 ml) and extracted with CH2Cl2 (3 Â 40 ml). The combined extracts were washed with brine,
dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by CC to afford the pure
product 13 as a colorless liquid (5.34 g, 85%). Rf (AcOEt/hexane 1:9) 0.8. [a]2D5 ¼ À19.56 (c ¼ 1.0,
CHCl3). IR (KBr): 2958, 2929, 2856, 1496, 1454, 1275, 1204, 1098, 738. 1H-NMR (300 MHz, CDCl3): 0.03
(s, 6 H); 0.90 (s, 9 H); 1.52 – 1.72 (m, 4 H); 3.47 (t, J ¼ 6.4, 2 H); 4.08 – 4.14 (m, 1 H); 4.50 (s, 2 H); 5.01 –
5.16 (m, 2 H); 5.75 – 5.83 (m, 1 H); 7.31 – 7.36 (m, 5 H). 13C-NMR (75 MHz, CDCl3): À 4.9; À 4.4; 18.2;
25.4; 25.8; 34.5; 70.4; 72.7; 73.5; 113.6; 127.4; 127.6; 128.2; 138.5; 141.5. HR-ESI-MS: 343.2175 ([M þ
Na]þ, C19H32NaO2Siþ; calc. 343.2172).
(R)-[(6-(Benzyloxy)hex-1-en-3-yl)oxy](tert-butyl)dimethylsilane (14) [20]. To a soln. of naphtha-
lene (3.60 g, 37.5 mmol) in THF (40 ml) was added small pieces of Li metal (0.19 g, 37.5 mmol). The
mixture was stirred at r.t. under Ar atmosphere, until the Li metal was completely dissolved. The
resulting dark green soln. of lithium naphthalenide was cooled to À 208 and then, a soln. of compound 13
(3.0 g, 9.3 mmol) in THF (50 ml) was added drop wise over 5 min. The resulting mixture was stirred at
À 208 for 70 min. Upon completion, the reaction was quenched with a sat. aq. NH4Cl soln. (20 ml) and
H2O (20 ml), and then, the mixture was extracted with AcOEt (3 Â 50 ml). The combined extracts were
washed with H2O and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product
was then purified by CC over SiO2 gives the pure product 14 (1.94 g, 90% yield) as a colorless oil. Rf
(AcOEt/hexane 3 :7) 0.5. [a]2D5 ¼ À19.42 (c ¼ 1.0, CHCl3). IR (KBr): 3234, 2928, 1594, 1365, 1178, 1045,
1
863, 793. H-NMR (300 MHz, CDCl3): 0.03 (s, 6 H); 0.89 (s, 9 H); 1.53 – 1.72 (m, 4 H); 3.48 (t, J ¼ 6.4,
2 H); 4.18 – 4.24 (m, 1 H); 5.04 – 5.18 (m, 2 H); 5.78 – 5.93 (m, 1 H). 13C-NMR (75 MHz, CDCl3): À 4.9;
À 4.4; 18.2; 25.4; 25.8; 34.5; 70.4; 72.7; 73.5; 118.6; 138.4. HR-ESI-MS: 231.1769 ([M þ H]þ, C12H27SiO2þ ;
calc. 231.1774).
(4R)-4-{[tert-Butyl(dimethyl)silyl]oxy}hex-5-enoic Acid (4). To the soln. of 14 (1.9 g, 8.2 mmol) in
CH2Cl2 (30 ml) at 08 were added TEMPO (650 mg, 4.1 mmol), and BAIB (5.32 g, 16.52 mmol). After
stirring at 08 for 2 h, 20% aq. Na2S2O3 soln. was added. The products were extracted with CHCl3, and the
org. layer was washed with a 20% aq. Na2S2O3 soln. and then dried (Na2SO4). Removal of the solvent
gave a crude aldehyde. The aldehyde was dissolved in MeCN (25 ml) and H2O (2.5 ml). To this soln. were
added 2-methylbut-2-ene (0.08 ml, 22.36 mmol), NaH2PO4 · 2 H2O (2.32 g, 14.91 mmol), and NaClO2
(1.34 g, 14.91 mmol), and the mixture was stirred at r.t. for 30 min. To this mixture was added a 1m aq.
citric acid soln. at 08, and the products were extracted with CHCl3, and then dried over MgSO4, filtered,
and concentrated in vacuo. The residue was purified by CC to afford the pure product 4 as colorless liquid
(1.49 g, 82%). Rf (AcOEt/hexane 3 :7) 0.4. [a]D25 ¼ À19.20 (c ¼ 1.0, CHCl3). IR (KBr): 2955, 2928, 1710,
1467, 1179, 1035, 833, 773. 1H-NMR (CDCl3, 300 MHz): 0.03 (s, 6 H); 0.89 (s, 9 H); 1.76 – 1.92 (m, 2 H);
2.36 – 2.46 (m, 2 H); 4.18 – 4.25 (m, 1 H); 5.05 – 5.19 (m, 2 H); 5.71 – 5.86 (m, 1 H). 13C-NMR (75 MHz,
CDCl3): À 5.0; À 4.6; 25.6; 25.9; 29.4; 32.4; 72.3; 115.6; 140.6; 180.2. HR-ESI-MS: 245.1564 ([M þ H]þ,
C12H25O3Siþ; calc. 245.1567).
(1S)-1-[(4S,5R)-5-Ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]octyl (4R)-4-{[tert-Butyl(dimethyl)silyl]-
oxy}hex-5-enoate (3) [15].To a stirred soln. of 4 (1.5 g, 6.1 mmol) were added N,Nꢀ-dicyclohexylcarbo-
dimide (DCC, 2.53 g, 12.2 mmol) and 4-(dimethylamino)pyridine (DMAP, 160 mg, 1.2 mmol) in CH2Cl2
(20 ml) at 08, followed by compound 5 (1.88 g, 7.3 mmol) at 08. The resulting mixture was stirred for 6 h at
r.t.. After completion, the mixture was filtered through a Celite pad which was then extracted with
CH2Cl2. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated in
vacuo. The residue was purified by CC to afford the pure product 3 (2.51 g, 85%) as colorless oil. Rf
(AcOEt/hexane 1:9) 0.8. [a]2D5 ¼ þ12.58 (c ¼ 1.0, CHCl3). IR (KBr): 2956, 2928, 2857, 1739, 1465, 1375,
1253, 1166, 1074, 837, 777. 1H-NMR (300 MHz, CDCl3): 0.04 (s, 6 H); 0.84 – 0.90 (m, 12 H); 1.22 – 1.34 (m,

Helvetica Chimica Acta – Vol. 98 (2015)
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10 H); 1.38 (s, 3 H); 1.48 (s, 3 H); 1.57 – 1.64 (m, 2 H); 1.75 – 1.83 (m, 2 H); 2.30 (t, J ¼ 9.0, 2 H); 4.14 –
4.20 (m, 2 H); 4.58 – 4.63 (m, 1 H); 4.88 – 4.92 (m, 1 H); 5.04 – 5.08 (m, 1 H); 5.14 – 5.24 (m, 2 H); 5.30 –
5.37 (m, 1 H); 5.74 – 5.85 (m, 2 H). 13C-NMR (75 MHz, CDCl3): À 5.0; À 4.5; 14.0; 22.6; 24.5; 25.2; 25.7;
25.8; 27.6; 29.2; 29.6; 29.7; 31.1; 31.8; 32.6; 71.8; 72.4; 78.4; 78.8; 108.7; 114.4; 118.4; 128.2; 128.8; 133.2;
140.7; 172.7. HR-ESI-MS: 483.3500 ([M þ H]þ, C27H51O5Siþ; calc. 483.3486).
(3aS,4S,9R,10E,11aR)-4-Heptyl-3a,4,7,8,9,11a-hexahydro-9-hydroxy-2,2-dimethyl-6H-[1,3]dioxo-
lo[4,5-c]oxecin-6-one (15) [6]. To a stirred soln. of 3 (2.5 g, 5.1 mmol) in THF (20 ml) was added
pyridine · HF (3.8 ml, 7.5 mmol) at 08. After stirring the mixture for 8 h at ambient temp., the reaction
was quenched with a sat. aq. NaHCO3 soln. (20 ml). The aq. layer was extracted with AcOEt (2 Â 20 ml).
The combined org. phases were dried (Na2SO4), and concentrated in vacuo. The residue was purified by
CC over SiO2 to afford the alcohol (1.52 g, 80%) as colorless liquid. To a stirred soln. of alcohol (1.5 g,
4.0 mmol) in dry CH2Cl2 (150 ml) under N2, Grubbsꢁ 2nd generation catalyst (172 mg, 0.2 mmol) was
added. The resulting mixture was heated to reflux for 6 h. After completion of the reaction, the solvent
was evaporated, and the crude residue was purified by CC to afford pure product 15 as a colorless oil
(1.1 g, 80%). Rf (AcOEt/hexane 2 :8) 0.6. [a]D25 ¼ À7.65 (c ¼ 1.2, CHCl3). IR (KBr): 3447, 2926, 2858,
1728, 1376, 1232, 1144, 1045, 974, 784. 1H-NMR (300 MHz, CDCl3): 0.87 (t, J ¼ 7.0, 3 H); 1.21 – 1.34 (m,
10 H); 1.38 (s, 3 H); 1.54 (s, 3 H); 1.74 – 1.85 (m, 2 H); 2.08 – 2.00 (m, 2 H); 2.37 – 2.31 (m, 2 H); 3.98 (dd,
J ¼ 10.0, 5.0, 1 H); 4.22 – 4.13 (m, 1 H); 4.70 – 4.67 (m, 1 H); 4.96 – 4.90 (m, 1 H); 5.66 (dd, J ¼ 9.0, 1.9,
1 H); 5.82 (dd, J ¼ 16.0, 3.3, 1 H). 13C-NMR (75 MHz, CDCl3): 14.1; 22.8; 24.6; 26.2; 28.4; 29.2; 29.5;
31.3; 31.8; 31.9; 33.6; 70.2; 75.5; 75.7; 78.6; 109.4; 126.7; 128.2; 175.0. HR-ESI-MS: 363.2143 ([M þ Na]þ,
C19H32NaOþ5 ; calc. 363.2145).
4-{[(3aS,4S,9R,10E,11aR)-4-Heptyl-3a,6,7,8,9,11a-hexahydro-2,2-dimethyl-6-oxo-4H-[1,3]dioxo-
lo[4,5-c]oxecin-9-yl]oxy}-4-oxobutanoic Acid (16) [17]. To a stirred soln. of 15 (0.5 g, 1.47 mmol),
succinic anhydride (294 mg, 2.94 mmol) and DMAP (179 mg, 1.47 mmol) in CH2Cl2 (20 ml) were added.
The resulting mixture was stirred for 8 h at r.t. and diluted with a sat. aq. NaHCO3 soln., and then
extracted with CH2Cl2. The org. layer was washed with brine, dried (Na2SO4), and concentrated under
reduced pressure. The crude residue was purified by CC over SiO2 to give the 16 (485 mg, 75%) as
yellowish oil. Rf (AcOEt/hexane 1:4) 0.7. Spectroscopic data: see [6].
Mangiferaelactone (¼4-{[(5R,6E,8R,9R,10S)-10-Heptyl-3,4,5,8,9,10-hexahydro-8,9-dihydroxy-2-
oxo-2H-oxecin-5-yl]oxy}-4-oxobutanoic Acid; 1) [18]. A mixture of compound 16 (100 mg, 0.22 mmol)
and CeCl3 · 7 H2O (170 mg, 0.45 mmol) in MeCN (5 ml) was stirred at 808 for 5 h as required to complete
the reaction. After completion of the reaction as indicated by TLC, the mixture was extracted with
AcOEt, and the combined org. layers were washed with H2O and brine, dried (Na2SO4), and
concentrated under reduced pressure to remove the solvent. The crude product was purified by CC to
afford the pure product 1 as yellowish-cream solid. (70 mg, 73%). Rf (AcOEt/hexane 4 :6) 0.5.
Spectroscopic data: see [6].
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Received April 25, 2015