Total synthesis of umuravumbolide

Article abstract of DOI:10.1002/hlca.201200078

A simple and efficient stereoselective total synthesis of (+)-umuravumbolide (1b) and (-)-deacetylumuravumbolide (1a) starting from commercially available pentanal is described. The synthesis involves Sharpless asymmetric epoxidation, Jacobsen's hydrolytic kinetic resolution (HKR), and the Yamaguchi oxirane opening as key steps (Scheme2).

Full text of DOI:10.1002/hlca.201200078

Helvetica Chimica Acta – Vol. 95 (2012)
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Total Synthesis of Umuravumbolide
by Vanam Shekhar, Dorigondla Kumar Reddy, and Yenamandra Venkateswarlu*
Division of Natural Products Chemistry, Natural Products Laboratory, Indian Institute of Chemical
Technology, Hyderabad-500 007, India
(phone: þ 91-40-27193167; fax: þ 91-40-27160512; e-mail: luchem@iict.res.in)
A simple and efficient stereoselective total synthesis of (þ)-umuravumbolide (1b) and (ꢀ)-
deacetylumuravumbolide (1a) starting from commercially available pentanal is described. The synthesis
involves Sharpless asymmetric epoxidation, Jacobsenꢀs hydrolytic kinetic resolution (HKR), and the
Yamaguchi oxirane opening as key steps (Scheme 2).
Introduction. – a,b-Unsaturated d-lactones are structural elements generally found
with diverse array of biological activity in natural products [1]. The a,b-unsaturated d-
lactone structural units are excellent potential Michael acceptors for nucleophilic
amino acid residues of the natural receptors [2]. They inhibit HIV protease [3], induce
apoptosis [4], and have even been shown to be antileukemic [5] and anticancer agents
[6]. Further, they have shown a variety of biological activities, such as plant-growth
inhibitors, pheromones, and antifeedant, antifungal, and antibacterial reagents [7]. In
recent times, we have been interested in the synthesis of natural products containing
pyranone units [8]. The two 2H-pyran-2-ones deacetylumuravumbolide and umur-
avumbolide were isolated from Tetradenia riparia (Lamiaceae) from central and
southern Africa [9]. The structures of (ꢀ)-deacetylumuravumbolide (1a) and (þ)-
umuravumbolide (1b) were revised by Davies-Coleman and Rivett, and they
determined the absolute configuration on the basis of NMR and CD spectral studies
and also reported the optical rotations of these compounds [10]. Recently, we reported
the synthesis of (ꢀ)-deacetylumuravumbolide (1a) and (þ)-umuravumbolide (1b) [11].
Herein, we report another simple and practical route for the synthesis of compounds 1a
and 1b using Sharpless asymmetric epoxidation and Jacobsenꢀs hydrolytic kinetic
resolution (HKR) as chirality-introducing steps, and the Yamaguchi method for the
oxirane-opening step.
Our retrosynthesis of (þ)-umuravumbolide (1b) and (ꢀ)-deacetylumuravumbolide
(1a), is depicted in Scheme 1 starting from pentanal (2).
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 1. Retrosynthetic Analysis
Results and Discussion. – As outlined in Scheme 2, pentanal (2) was subjected to a
Wittig reaction with (ethoxycarbonylmethylene)triphenylphosphorane in dry CH2Cl2
to furnish a,b-unsaturated ester 3 with trans-configuration in 87% yield. Reduction of
Scheme 2
a) PPh3CHCO2Et, CH2Cl2, 6 h, r.t.; 87%. b) DIBAL-H, dry CH2Cl2, 08, 2 h; 90%. c) (þ)-Diethyl l-
tartrate, cumene hydroperoxide, Ti(OiPr)4, dry CH2Cl2, ꢀ 208, 12 h; 80%. d) 1. PPh3, CCl4, NaHCO3,
reflux, 6 h; 78%; 2. BuLi, dry THF, 10 min; 70%. e) 1. tBuPh2SiCl, 1H-imidazole, dry CH2Cl2, 3 h, 08 to
r.t.; 93%; 2. BuLi, DMF, dry THF, ꢀ 788, 1 h; 65%. f) Lindlarꢀs catalyst, CH2Cl2, H2, 8 h; 85%. g)
(Me3S)I, 50% aq. NaOH soln., (Bu4N)I, CH2Cl2, 408, 24 h; 84%. h) (S,S)-Jacobsen catalyst, H2O, r.t.,
72 h; 40%. i) HCꢁCCO2Et, BuLi, BF3 · Et2O, dry THF, ꢀ 788, 2 h; 79%. j) Lindlarꢀs catalyst, benzene,
H2; 88%. k) PPTS, CHCl3, reflux, 4 h, 95%. l) Et3N · 3 HF, MeCN, 12 h, 94%. m) Ac2O, pyridine, CH2Cl2,
18 h; 97%.

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the ethyl ester with diisobutylaluminum hydride (DIBAL-H) at 08 afforded the
corresponding alcohol 4 in 90%, which was subjected to Sharpless asymmetric
epoxidation [12] with (þ)-diethyl l-tartrate, cumene hydroperoxide (¼1-methyl-1-
phenylethyl hydroperoxide), and Ti(OiPr)4 in CH2Cl2 to give the desired oxiraneme-
thanol 5 in 80% yield with an enantiomer excess (e.e.) of 99.2%. Oxiranemethanol 5
was converted into the corresponding (chloromethyl)oxirane [13] with Ph3P and a
catalytic amount of NaHCO3 in refluxing CCl4; then the (chloromethyl)oxirane was
transformed to the chiral alkynol [14] 6 in 70% yield under base-induced oxirane ring
opening with BuLi in dry THF. The secondary alcohol 6 was protected with (tert-
butyl)chlorodiphenylsilane (tBuPh2SiCl) in the presence of 1H-imidazole to give the
silyl ether in 93% yield. The latter was formylated with DMF and BuLi in dry THF to
provide alkynal 7 in 65% yield. This aldehyde 7 was converted to the required (Z)-
alkenal 8 in 85% yield by hydrogenation over Lindlarꢀs catalyst in dry CH2Cl2. Then
alkenal 8 was converted into oxirane 9 by reaction with trimethylsulfonium iodide
(1.0 equiv.) and 50% aqueous NaOH in the presence of tetrabutylammonium iodide
(catalytic amount) in CH2Cl2 [15]. Oxirane 9 was a 1:1.3 mixture of the two
diastereoisomers which could not be differentiated by TLC. The resulting diaster-
1
eoselectivity was determined from H- and 13C-NMR data. The next step in the
synthesis was to produce the diastereoisomerically pure oxirane by means of Jacobsenꢀs
hydrolytic kinetic resolution (HKR). Thus, oxirane 9 was subjected to the HKR [16]
with [Co(OAc){(S,S)-salen}] complex (0.5 mol-%) and H2O (0.55 equiv.) in THF
(0.55 equiv.) at room temperature to afford (S)-oxirane 10 in 40% yield and the diol in
52% yield.
Our next concern was the construction of the key 2H-pyran-2-one moiety of the
target compounds. Hence, employing the Yamaguchi procedure [17], oxirane 10 was
treated with the lithium salt of ethyl prop-2-ynate in dry THF at ꢀ 788 to furnish 11 in
79%, which was then subjected to partial reduction over Lindlarꢀs catalyst in benzene
to afford compound 12 in 88% yield. The latter was then subjected to lactonization with
pyridinium p-toluenesulfonate (¼ pyridinium 4-methylbenzenesulfonate; PPTS) in
t
CHCl3 to afford 2H-pyran-2-one 13 in 95%. The BuPh2Si ether group of 13 was
removed with triethylamine tris(hydrofluoride) in MeCN to afford the natural product
(ꢀ)-deacetylumuravumbolide (1a) in 94% yield. The latter was acetylated with Ac2O/
pyridine to afford (þ)-umuravumbolide (1b) in 97% yield. The physical and optical
data of 1a (optical purity 98.0%) and of 1b (optical purity 99.0%) were in close
agreement with the ones reported for the natural products 1a and 1b, respectively [10]
(see Exper. Part).
Conclusions. – We accomplished the total synthesis of the umuravumbolides
starting from pentanal employing Sharpless asymmetric epoxidation, Jacobsenꢀs
hydrolytic kinetic resolution (HKR), the Yamaguchi oxirane-opening method, and
acid-catalyzed lactonization. This synthetic sequence provides an easy access to the
preparation of umuravumbolides.
The authors are thankful to CSIR, New Delhi, India, for the financial support and Dr. J. S. Yadav,
Director, Indian Institute of Chemical Technology (IICT), for his encouragement.

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Experimental Part
General. Solvents were dried over standard drying agents and freshly distilled prior to use. The
reagents were purchased from Aldrich and Acros and were used without further purification unless
otherwise stated. All moisture-sensitive reactions were carried out under N2. Org. solns. were dried
(Na2SO4) and concentrated in vacuo below 408. Column chromatography (CC): silica gel (Acmeꢀs 60 –
120 mesh). Optical rotations: Horiba high-sensitive polarimeter SEPA-300; at 258. IR Spectra: Perkin-
Elmer-IR-683 spectrophotometer with NaCl optics; ˜n in cmꢀ1 1H- and 13C-NMR Spectra: Bruker-
,
Avance-300 instrument; at 300 and 75 MHz, resp.; in CDCl3; d in ppm rel. to SiMe4 as internal standard, J
in Hz. MS: Agilent-Technologies-1100 spectrometer (Agilent Chemistation software); in m/z.
Ethyl (2E)-Hept-2-enoate (3). To a stirred soln. of pentanal (2; 1.9 g, 21.62 mmol) in CH2Cl2 (60 ml)
was added (ethoxycarbonylmethylene)triphenylphosphorane (9 g, 25.95 mmol) at r.t. and stirred for 3 h.
After completion of the reaction, the mixture was diluted with H2O and extracted with CH2Cl2 (3 ꢂ
15 ml), the extract dried (Na2SO4), and concentrated and the crude residue purified by CC (AcOEt/
hexane 1:99): pure 3 (2.5 g, 87%). Colorless liquid. IR (neat): 2925, 2854, 1724, 1655, 1465, 1366, 1127,
721. 1H-NMR: 6.93 (dt, J ¼ 15.0, 7.1, 1 H); 5.76 (dt, J ¼ 15.0, 1.3, 1 H); 4.15 (q, J ¼ 7.1, 2 H); 2.2 (q, J ¼ 7.9,
2 H); 1.33 – 1.52 (m, 4 H); 1.29 (t, J ¼ 7.1, 3 H); 0.92 (t, J ¼ 7.1, 3 H ) . 13C-NMR: 165.8; 149.0; 121.0; 59.4;
31.3; 29.7; 21.7. ESI-MS: 156 (Mþ).
(2E)-Hept-2-en-1-ol (4). To a cooled (08) soln. of 3 (1.9 g, 12.10 mmol) in dry CH2Cl2 (40 ml) was
added DIBAL-H (2.58 g, 18.16 mmol, 20% soln. in toluene) within 15 min, and the mixture was stired at
r.t. for 2 h. After completion of the reaction, the mixture was quenched with MeOH (1ml) and sodium
potassium tartrate soln. (5 ml). The mixture was passed through a short pad of Celite. The filtrate was
concentrated and the residue purified by CC (AcOEt/hexane 1:9): 4 (1.25 g, 90%). Colorless liquid. IR
(neat): 3446, 2923, 2854, 1640, 1460, 1171, 769. 1H-NMR: 5.54 – 5.70 (m, 2 H); 4.04 (d, J ¼ 4.5, 2 H); 2.01 –
2.07 (m, 2 H); 1.24 – 1.42 (m, 4 H); 0.91 (t, J ¼ 6.8, 3 H). 13C-NMR: 62.98; 70.43; 73.68; 81.33; 120.61;
127.85; 127.94; 128.47; 134.57; 137.72. ESI-MS: 226 ([M þ NH4]þ).
(2R,3R)-3-Butyloxirane-2-methanol (5). To a cooled (ꢀ208) suspension of 4 ꢃ powdered activated
molecular sieves in dry CH2Cl2 (10 ml) were added Ti(OiPr)4 (0.58 ml, 1.96 mmol) and (þ)-diethyl l-
tartrate (0.4 g, 1.96 mmol) in dry CH2Cl2 (10 ml), and the mixture was stirred for 30 min at ꢀ 208. Then 4
(1.1 g, 9.8 mmol) in dry CH2Cl2 (20 ml) was added and the mixture stirred for another 30 min at ꢀ 208,
followed by cumene hydroperoxide (2.23 ml, 14.7 mmol) addition and subsequent stirring at ꢀ 208 for
5 h. After completion of the reaction, the mixture was quenched with H2O (1 ml) and stirred for 1 h at r.t.
After that, 30% aq. NaOH soln. (5 ml) and sat. NaCl soln. (1 ml) were added, and the mixture was stirred
vigorously for another 30 min at r.t. The resulting mixture was then filtered through Celite rinsing with
CH2Cl2. The aq. phase was extracted with CH2Cl2, the combined org. phase washed with brine, dried
(Na2SO4), and concentrated, and the residue purified by CC (AcOEt/hexane 1:9): 5 (1.14 g, 80%).
Viscous liquid. [a]2D5 ¼ ꢀ44.4 (c ¼ 0.25, CHCl3), e.e. ¼ 99.2% (determined by chiral HPLC (Zorbax-SBC-
1
3 column (150 ꢂ 4.6 mm, 20 mm), Me3CN/H2O 7:3)). IR (neat): 3408, 2930, 2866, 1088. H-NMR: 3.85
(d, J ¼ 12.8, 1 H); 3.53 – 3.61 (m, 1 H); 2.83 – 2.93 (m, 2 H); 2.15 (s, 1 H); 1.52 – 1.61 (m, 2 H); 1.32 – 1.49
(m, 4 H); 0.93 (t, J ¼ 6.8, 3 H). 13C-NMR: 72.03; 63.30; 62.48; 32.67; 28.10; 22.66; 14.13. EI-MS: 130
(Mþ).
(3S)-Hept-1-yn-3-ol (6). A soln. of 5 (1.43 g, 11 mmol), Ph3P (4.66 g, 16.5 mmol), and NaHCO3
(497 mg, 5.5 mmol) in CCl4 (15 ml) under N2 was refluxed for 3 h. After completion of the reaction, the
solvent was evaporated and the residue purified by CC (5% AcOEt/hexane): (chloromethyl)oxirane
(1.27 g, 78%). Yellow oil. 1H-NMR: 3.60 (dd, J ¼ 11.7, 5.9, 1 H); 3.38 (dd, J ¼ 11.7, 5.9, 1 H); 2.92 (td, J ¼
5.9, 2.2, 1 H); 2.79 (td, J ¼ 5.9, 2.2, 1 H); 1.60 – 1.54 (m, 2 H); 1.50 – 1.33 (m, 4 H); 0.93 (t, J ¼ 6.8, 3 H).
The (chloromethyl)oxirane (1.18 g, 8 mmol) was taken up in cooled (ꢀ 788) dry THF (15 ml), 1.6m
BuLi in hexane (16 ml, 24 mmol) was added dropwise, and the mixture was stirred for 10 min. After
completion of the mitxture, the reaction was quenched with sat. aq. NH4Cl soln. (15 ml) and H2O
(15 ml). The resulting soln. was extracted with Et2O (3 ꢂ 30 ml), the extract washed with brine, dried
(Na2SO4), and concentrated, and the crude product purified by CC (AcOEt/hexane 1:9): 6 (675 mg,
70%). [a]2D5 ¼ ꢀ20 (c ¼ 0.7, CHCl3). IR (neat): 3445, 2926, 1634, 1035, 761. 1H-NMR: 4.31 (td, J ¼ 6.4, 2.1,

Helvetica Chimica Acta – Vol. 95 (2012)
1597
1 H); 2.30 (s, 1 H); 1.71 – 1.62 (m, 2 H); 1.47 – 1.26 (m, 4 H); 0.92 (t, J ¼ 6.8, 3 H). 13C-NMR: 72.8; 67.5;
62.3; 37.3; 27.8; 27.7; 13.9. EI-MS: 112 (Mþ).
(4S)-4-{[(tert-Butyl)diphenylsilyl]oxy}oct-2-ynal (7). To a cooled (08) soln. of 6 (2.5 g, 12.13 mmol)
and 1H-imidazole (2.06 g, 30.25 mmol) in dry CH2Cl2 (30 ml) was added dropwise (tert-butyl)chloro-
diphenylsilane (4.0 g, 14.55 mmol) and the mixture was stirred for 4 h. After completion of the reaction,
the mixture was diluted with H2O (20 ml) and extracted with CH2Cl2 (3 ꢂ 30 ml). The combined org.
layer was washed with brine (10 ml), dried (Na2SO4), and concentrated, and the crude residue purified
ny CC (AcOEt/hexane 5 :95) to give the silyl ether of 6 (2.2 g, 93%) as yellow liquid. The silyl ether was
used for the next reaction. To a cooled (ꢀ 788) soln. of this silyl ether (4.96 g, 21.85 mmol) in dry THF
(50 ml) was added 2.5m BuLi in hexane (10.5 ml, 26.25 mmol), and the mixture was stirred for 10 min,
followed by the addition of DMF (3.19 g, 43.7 mmol) and subsequent stirring for 1 h. After completion of
the reaction, the mixture was quenched with aq. dil. (1%) HCl soln. (40 ml). The product was extracted
with Et2O (3 ꢂ 50 ml), the extract dried (MgSO4) and, concentrated, and the residue subjected to CC
(hexane/AcOEt 9 :1): pure 7 (2.89 g, 65%). [a]2D5 ¼ ꢀ23.5 (c ¼ 2, CHCl3). IR (neat): 2956, 2932, 2859,
1
2208, 1670, 1109, 702. H-NMR: 9.01 (s, 1 H); 7.73 – 7.57 (m, 4 H); 7.48 – 7.28 (m, 6 H); 4.52 – 4.45 (m,
1 H); 1.78 – 1.64 (m, 1 H); 1.54 – 1.19 (m, 5 H); 0.86 (t, J ¼ 6.8, 3 H). 13C-NMR: 176.5; 135.9; 135.7; 132.9;
132.8; 130.0; 129.9; 127.7; 127.5; 97.8; 84.1; 63.6; 37.1; 26.8; 22.2; 19.2; 13.8.
(2S,4Z)-4-{[(tert-Butyl)diphenylsilyl]oxy}oct-2-enal (8). A soln. of 7 (1.88 g, 4.98 mmol) in dry
CH2Cl2 (20ml) and Lindlarꢀs catalyst (0.5g) were stirred under H2 (TLC monitoring). After completion
of the reaction (10 h), the mixture was filtered through a silica gel pad, the solvent evaporeted, and
residue purified by CC (hexane/AcOEt 98 :2): pure 8 (1.6 g, 85%). Liquid. [a]2D5 ¼ þ15.1 (c ¼ 1.65,
CHCl3). IR (neat): 2957, 2932, 2859, 1688, 1466, 1428, 1109, 703. 1H-NMR: 9.29 (d, J ¼ 8.0, 1 H); 7.65 –
7.57 (m, 4 H); 7.42 – 7.30 (m, 6 H); 6.39 (dd, J ¼ 11.2, 8.8, 1 H); 5.64 (dd, J ¼ 11.2, 7.2, 1 H); 4.92 (q, J ¼
15.2, 6.4, 1 H); 1.75 – 1.45 (m, 2 H); 1.28 – 1.17 (m, 4 H); 1.06 (s, 9 H); 0.86 (t, J ¼ 6.8, 3 H). 13C-NMR:
190.4; 153.1; 135.7; 135.6; 133.3; 133.2; 130.8; 129.9; 129.4; 128.1; 127.6; 127.5; 68.8; 37.4; 26.8; 22.3; 19.1;
13.8.
(tert-Butyl){[(1S,2Z)-1-butyl-3-(oxiran-2-yl)prop-2-en-1-yl]oxy}diphenylsilane (9). To a soln. of 8
(1.9 g, 5 mmol) and (Bu4N)(0.065mmol) in CH2Cl2 (25 ml) were added 50% aq. NaOH soln. and
trimethylsulfonium iodide (102 mg, 5 mol). The was heated at 508 with vigorous stirring for 48 h
whereupon the originally undissolved sulfonium salt had disappeared. After completion of the reaction,
the mixture was poured on ice, the org. phase washed with H2O, dried (Na2SO4), and concentrated, and
the residue purified by CC (hexane/AcOEt 9 :1): 1:1.3 diastereoisomer mixture 9 (1.65 g, 84%). Liquid.
[a]2D5 ¼ þ2.5 (c ¼ 0.6, CHCl3). ESI-MS: 395 ([M þ 1]þ).
(tert-Butyl){[(1S,2Z)-1-butyl-3-[(2S)-oxiran-2-yl]prop-2-en-1-yl]oxy}diphenylsilane (10). To a
cooled (08) soln. of 9 (0.9 g, 2.31mmol) in THF (0.3ml) was added [CoIII(OAc){(S,S)-salen}] (8 mg,
0.012 mmol). The mixture was stirred for 5 min, and then dist. H2O (22.9 ml, 1.27 mmol) was added. After
stirring for 72 h, this mixture was concentrated and purified by CC (petroleum ether/AcOEt 9 :1): liquid
10 (360 mg, 40%) and on elution with petroleum ether/AcOEt 3 :2, liquid diol 10 (468 mg, 52%): [a]D25
¼
ꢀ10.3 (c ¼ 0.6, CHCl3). IR (neat): 2932, 2858, 1426, 1106. 1H-NMR: 7.64 – 7.71 (m, 4 H); 7.31 – 7.43 (m,
6 H); 5.66 – 5.76 (m, 1 H); 4.75 – 4.89 (m, 1 H); 4.47 – 4.57 (m, 1 H); 2.87 – 2.93 (m, 1 H); 2.46 (dd, J ¼ 5.3,
3.0, 1 H); 2.31 (dd, J ¼ 5.3, 3.0, 1 H); 1.44 – 1.71 (m, 2 H); 1.13 – 1.24 (m, 4 H); 1.05 (s, 9 H); 0.82 (t, J ¼ 6.8,
3 H). 13C-NMR: 138.8; 135.9; 135.8; 129.5; 129.4; 127.6; 127.5; 127.3; 127.0; 126.8; 69.6; 48.0; 47.7; 37.8;
26.9; 22.5; 19.2; 15.4; 13.9. ESI-MS: 395 ([M þ H]þ). HR-ESI-MS: 395.2403 ([M þ H]þ, C25H35O2Siþ;
calc. 395.2401).
Ethyl (5R,6Z,8S)-8-{[(tert-Butyl)diphenylsilyl]oxy}-5-hydroxydodec-6-en-2-ynoate (11). To cooled
(ꢀ 788) soln. of ethyl prop-2-ynoate (588 mg, 6.6 mmol) in anh. THF (15 ml) was added dropwise 1.6m
BuLi in hexane (4.2 ml, 6.64 mmol) and the mixture was stirred for 15 min, followed by addition of BF3 ·
Et2O (0.84 ml, 6.6 mmol) and subsequent stirring for an additional 15 min. Once the formation of dark
black alkynyl borane was observed, a soln. of 10 (260 mg, 0.66 mmol) in anh. THF (10 ml) was added to
the above soln. and stirred for 30 min at ꢀ 788. After completion of the reaction, the mixture was
quenched at ꢀ 788 by addition of sat. Na2SO4 soln. (20 ml) and AcOEt/H2O. The mixture was extracted
with AcOEt, the combined org. phase washed with brine, dried (Na2SO4), and concentrated, and the
crude residue purified by CC (20% AcOEt/petroleum ether): pure 11 (256 mg, 79%). [a]2D5 ¼ ꢀ36.0 (c ¼

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1
0.3, CHCl3). IR (neat): 3449, 2928, 2857, 2236, 1712, 1250, 1105, 1055. H-NMR: 7.62 – 7.70 (m, 4 H);
7.35 – 7.45 (m, 6 H); 5.64 – 5.75 (m, 1 H); 5.05 – 5.22 (m, 1 H); 4.32 – 4.41 (m, 1 H); 4.25 (q, J ¼ 6.9, 7.2,
2 H); 3.94 – 4.03 (m, 1 H); 3.54 – 2.90 (m, 2 H); 1.46 – 1.63 (m, 2 H); 1.34 (t, J ¼ 7.2, 3 H); 1.16 – 1.28 (m,
4 H); 1.06 (s, 9 H); 0.85 (t, J ¼ 6.8, 3 H). 13C-NMR: 157.01; 137.6; 135.9; 135.8; 129.8; 129.7; 129.6; 127.5;
127.4; 122.6; 122.3; 88.43; 69.79; 69.15; 64.32; 61.93; 37.99; 33.87; 33.34; 29.70; 26.99; 22.62; 13.96. ESI-
MS: 515 ([M þ Na]þ). HR-ESI-MS: 515.2585 ([M þ Na]þ, C30H40NaO4Si þ, calc. 515.2588).
Ethyl (2Z,5R,6Z,8S)-8-{[(tert-Butyl)diphenylsilyl]oxy}-5-hydroxydodeca-2,6-dienoate (12). A sus-
pension of 11 (197 mg, 0.4 mmol) and Lindlarꢀs catalyst (100 mg) in benzene (15 ml) was flushed with H2
gas and stirred for 5 h under H2 (TLC monitoring). After completion, the mixture was filtered (Celite),
the filtrate concentrated, and the residue purified by CC (20% AcOEt/petroleum ether): 12 (174 mg,
88%). Oil [a]2D5 ¼ ꢀ8.0 (c ¼ 0.2, CHCl3). IR: 3450, 2928, 2857, 2096, 1731, 1635, 1463, 1221 1076, 771,
1388, 1251, 1045, 918, 796, 742, 618, 621. 1H-NMR: 7.77 – 7.64 (m, 4 H); 7.48 – 7.33 (m, 6 H); 5.90 – 5.50 (m,
3 H); 5.10 – 4.94 (m, 1 H); 4.55 – 4.47 (m, 1 H); 4.16 – 3.85 (m, 3 H); 3.12 – 3.54 (m, 2 H); 1.52 – 1.60 (m,
2 H); 1.32 (t, J ¼ 7.2, 3 H); 1.14 – 1.28 (m, 4 H); 1.02 (s, 9 H); 0.84 (t, J ¼ 6.8, 3 H). 13C-NMR: 166.9; 147.9;
137.3; 135.9; 135.8; 129.5; 129.4; 127.5; 127.4; 126.0; 125.7; 121.0; 120.5; 69.9; 65.9; 60.2; 53.4; 40.6; 38.3;
29.6; 26.9; 22.6; 19.2; 13.9. ESI-MS: 517 ([M þ Na]þ).
(6R)-6-{(1Z,3S)-3-{[(tert-Butyl)diphenylsilyl]oxy}hept-1-en-1-yl}-5,6-dihydro-2H-pyran-2-one (13).
A soln. of 12 (168 mg, 0.34 mmol) and PPTS (170 mg, 0.68 mmol) in CHCl3 (10 ml) was refluxed for 6 h.
After completion of the reaction, the mixture was diluted with H2O (10 ml) and extracted with CHCl3
(3 ꢂ 50 ml). The combined org. layer was washed with brine, dried (Na2SO4), and concentrated and the
resulting crude product purified by CC (20% AcOEt/petroleum ether): 13 (152 mg, 95%). Pale yellow
oil. [a]2D5 ¼ ꢀ11.1 (c ¼ 0.45, CHCl3). IR (neat): 2929, 2857, 1735, 1464, 1225, 1078, 703. 1H-NMR: 7.69 –
7.63 (m, 4 H); 7.44 – 7.34 (m, 6 H); 6.40 (dd, J ¼ 9.8, 4.0, 1 H); 5.96 (dd, J ¼ 9.8, 2.3, 1 H); 5.89 – 5.77 (m,
1 H); 5.71 – 5.62 (m, 1 H); 5.09 – 4.95 (m, 1 H); 4.39 – 4.31 (m, 1 H); 2.89 – 2.70 (m, 2 H); 1.60 – 1.53 (m,
2 H); 1.31 – 1.19 (m, 4 H); 1.04 (s, 9 H); 0.86 (t, J ¼ 6.8, 3 H). 13C-NMR: 165.0; 148.9; 137.6; 135.9; 135.8;
129.8; 129.7; 127.6; 127.5; 123.1; 123.0; 120.1; 120.0; 70.0; 69.2; 37.9; 33.0; 29.6; 26.8; 22.6; 19.2; 13.9. ESI-
MS: 471 ([M þ Na]þ). HR-ESI-MS: 471.2345 ([M þ Na]þ, C28H36NaO3Siþ; calc.: 471.2326).
(ꢀ)-Deacetylumuravumbolide (¼(1R)-5,6-Dihydro-6-[(1Z,3S)-3-hydroxyhept-1-en-1-yl]2H-pyran-
2-one; 1a). To a soln. of 13 (235 mg, 0.5 mmol) in MeCN (4 ml) was added Et3N · 3 HF (0.6 g, 4.0 mmol)
and stirred for 12 h. After completion of the reaction, the mixture was diluted with H2O and extracted
with AcOEt (3 ꢂ 25 ml). The extract was dried (MgSO4) and concentrated, and the crude product
subjected to CC (hexane/AcOEt 3 :2): 1a (98 mg 94%). [a]2D5 ¼ ꢀ5.4 (c ¼ 1, CHCl3), optical purity 98.0%
(natural product 1a [10]: [a]2D4 ¼ ꢀ5.3 (c ¼ 1.3, CHCl3); synthetic 1a [11b]: [a]D25 ¼ ꢀ5.4 (c ¼ 1, CHCl3)).
1
IR (neat): 3429, 2924, 2855, 1726, 1377, 1243, 1082. H-NMR: 6.88 (m, 1 H); 6.0 (dd, J ¼ 9.8, 2.2, 1 H);
5.60 – 5.73 (m, 2 H); 5.25 – 5.36 (m, 1 H); 4.33 – 4.47 (m, 1 H); 2.34 – 2.51 (m, 2 H); 2.2 (s, 1 H); 1.45 – 1.70
(m, 2 H); 1.20 – 1.42 (m, 4 H); 0.88 (t, J ¼ 6.9, 3 H). 13C-NMR: 163.8; 144.9; 137.9; 127.4; 121.4; 73.7; 67.7;
36.8; 29.9; 27.5; 22.6; 14.0. ESI-MS: 211 ([M þ H]þ). HR-ESI-MS: 211.1323 ([M þ H]þ, C12H19Oþ3 ; calc.
211.1329).
(þ)-Umuravumbolide (¼(6R)-6-[(1Z,3S)-3-(Actyloxy)hept-1-en-1-yl]-5,6-dihydro-2H-pyran-2-
one; 1b). To a soln. of 1a (52 mg, 0.25 mmol) and pyridine (80 mg, 1 mmol) in CH2Cl2 (1 ml) was
added Ac2O (0.05 g, 0.5 mmol) and stirred for 18 h. After completion of the reaction, the mixture was
diluted with cold H2O and extracted with CH2Cl2 (3 ꢂ 15 ml). The combined extract was dried (Na2SO4)
and concentrated, and the crude residue subjected to CC (hexane/AcOEt 8 :2): 1b (61 mg, 97%). [a]D25
¼
þ33.4 (c ¼ 1, CHCl3), optical purity 99.0% (natural product 1b [10]: [a]2D0 ¼ þ30.0 (c ¼ 2.1, CDCl3);
synthetic 1b [11b]: [a]2D5 ¼ þ33.4 (c ¼ 1, CDCl3) [11b]. IR (neat): 2929, 2860, 1747, 1730, 1242. 1H-NMR:
6.88 (m, 1 H); 6.01 (dd, J ¼ 9.8, 2.2, 1 H); 5.71 (dd, J ¼ 11.1, 8.0, 1 H); 5.31 – 5.56 (m, 3 H); 2.28 – 2.57 (m,
2 H); 2.02 (s, 3 H); 1.44 – 1.75 (m, 2 H); 1.20 – 1.43 (m, 4 H); 0.87 (t, J ¼ 6.9, 3 H). 13C-NMR: 170.1; 163.4;
144.2; 131.7; 130.0; 121.7; 74.0; 69.5; 34.3; 30.1; 27.3; 22.5; 22.2; 17.0; 14.0. ESI-MS: 253 ([M þ 1]þ).

Helvetica Chimica Acta – Vol. 95 (2012)
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Received February 16, 2012