Synthesis of pteroenone and its stereoisomers, a defensive metabolite of the abducted antarctic pteropod clione antarctica

Article abstract of DOI:10.1002/hlca.201000258

Four stereoisomers of (+)-pteroenone, a defensive metabolite of the abducted Antarctic pteropod Clione antarctica, were synthesized by employing anti-/syn-selective aldol reactions as the key step. These compounds displayed no antifeedant activity against

Full text of DOI:10.1002/hlca.201000258

Helvetica Chimica Acta – Vol. 93 (2010)
1933
Synthesis of Pteroenone and Its Stereoisomers, a Defensive Metabolite of the
Abducted Antarctic Pteropod Clione antarctica
by Hiroki Asaoa), Yoko Nakamuraa), Yukito Furuyaa), Shigefumi Kuwaharaa), Bill J. Bakerb),
and Hiromasa Kiyota*a)
a) Graduate School of Agricultural Sciences, Tohoku University, 1-1 Tsutsumidori-Amamiya,
Aoba-ku, Sendai 981-8555, Japan (phone/fax: þ 81-22-717-8785, e-mail: kiyota@biochem.tohoku.ac.jp)
b) Department of Chemistry, University of South Florida, 4202 E. Fowler Ave SCA400, Tampa,
FL 33620, USA
Four stereoisomers of (þ)-pteroenone, a defensive metabolite of the abducted Antarctic pteropod
Clione antarctica, were synthesized by employing anti-/syn-selective aldol reactions as the key step. These
compounds displayed no antifeedant activity against a generally benthic Antarctic fish that does not co-
occur with this pteropod.
1. Introduction. – The pteropod Clione antarctica is a shell-less, pelagic mollusc
which blooms each austral summer in McMurdo Sound, Antarctica. It has an appealing
shape, with its mantle adapted as wing-like appendages, and is called a ꢀsea butterflyꢁ. It
produces a defensive metabolite, called pteroenone, which shows antifeedant activity
against its predatory fishes [1][2]. There is a curious commensalism between C.
antarctica and an Antarctic hyperiid amphipod, Hyperiella dilatata, which is a prey of
several Antarctic fishes. Predatory fishes do not eat the amphipod grasping a pteropod
on its dorsum, due to a feeding deterrent produced by the pteropod [1][2]. Yoshida
et al. isolated a defensive chemical substance, named pteroenone ((þ)-(5R,6S)-1; Fig.),
and elucidated its configuration [2]. We have synthesized natural (5R,6S)-1 and
confirmed the absolute configuration [3][4]. In this article, the synthesis of four
stereoisomers of 1 and their antifeedant activity against Antarctic fishes are described.
Figure. Structure of pteroenone
2. Results and Discussion. – 2.1. Synthesis of (þ)-1 via a Weinreb Amide. First,
synthesis of natural 1 via Weinreb amide was examined. Although pteroenone is a
simple molecule, it could be very unstable due to the presence of conjugated diene
ꢂ 2010 Verlag Helvetica Chimica Acta AG, Zꢃrich

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Helvetica Chimica Acta – Vol. 93 (2010)
system adjacent to anti-aldol moiety. Thus, mild reaction conditions and easily
removable protecting groups should be used for its synthesis to avoid some unwanted
side reactions such as epimerization, retro-aldol/aldol reaction, polymerization,
dehydration, etc.
Scheme 1 depicts our previous synthetic studies reported in [3][4]. The key reaction
were Evansꢁ anti-aldol reaction [5] of (S)-2 [6] with 3 [7], and alkylation via Weinreb
amides [8], but the yield was low. In addition, the first trial of the deprotection of the
Et3Si (TES) group using HF/Bu4NF (TBAF) (pH 4) gave (þ)-(5R,6S)-1 with 72% de
(vide infra). The details are described in the Exper. Part.
Scheme 1. Synthesis of (þ)-(5R,6S)-1 via Weinreb Amides
a) MgCl2 (0.2 equiv.), Me3SiCl (TMSCl; 1.5 equiv.), Et3N (2 equiv.), AcOEt, r.t., 1 d. b) aq. H2O2/
MeOH; recrystallization. c) d) Me(MeO)NH · HCl (3 equiv.), AlMe3 (3 equiv.), CH2Cl2, ꢀ 20 to 208. e)
PrMgBr (3 equiv.), THF, 08. f) Triethylsilyl trifluoromethanesulfonate (TESOTf; 1.1 equiv.), 2,6-
lutidine (1.2 equiv.), CH2Cl2, ꢀ 558. g) PrLi (3 equiv.), THF, ꢀ 708. h) aq. HF/Bu4NF (TBAF), THF
(pH 4).
2.2. Synthesis of syn-Isomers via a Weinreb Amide. We also applied this scheme to
the synthesis of the syn-isomers (Scheme 2). Evansꢁ syn-aldol reaction [6] afforded
pure syn-5 as an oil (> 98% de). Transformation of syn-5 to the Weinreb amide syn-6
proceeded in 82% yield, and a by-product like 7 was not formed1). However, alkylation
of syn-6 to (þ)-(5S,6S)-1 resulted in low yield, and epimerization and retro-aldol
reaction (to form aldehyde 3) occurred during the reaction. A similar conversion with
1
)
Conversion of Evansꢁ syn-aldols to Weinreb amides were reported, see [9].

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Scheme 2. Synthesis of (þ)-(5S,6S)-1 via Weinreb Amide
a) (S)-2 (1.05 equiv.), Dibutylboron trifluoromethanesulfonate (Bu2BOTf; 1.15 equiv.), Et3N (1.2
equiv.), CH2Cl2, 08. b) Me(MeO)NH · HCl, AlMe3, THF, ꢀ 208. c) PrMgBr, THF, ꢀ 20 to 08. d)
Triethylsilyl trifluoromethanesulfonate (TESOTf), 2,6-lutidine, CH2Cl2, ꢀ 308. e) PrLi (2.5 equiv.),
THF, ꢀ 708. f) see Scheme 4.
the OH group protected with TES also resulted in low yield (!syn-8 ! syn-9 ! (þ)-
(5S,6S)-1).
2.3. Synthesis of (þ)-1 and (ꢀ)-1 via Thiol Esters. Since conversion via the Weinreb
amides was troublesome, that of the corresponding thiol esters were examined instead.
Scheme 3 shows the new route to anti-isomers. This scheme was described in part in
[3][4]. The OH group of anti-5 was protected as its TES ether to give anti-10. Use of the
EE (1-ethoxyethyl) group was also checked but failed in the final step2). The chiral
auxiliary was reductively removed via thio ester anti-11 [10] to afford aldehyde anti-
123). Introduction of the Pr fragment was unexpectedly troublesome. The reaction
could be carried out under cryogenic conditions using minimal nucleophile concen-
trations to avoid the removal of the TES group. As shown in the Table, PrLi in Et2O
gave the best result, and the resulting OH group of anti-13 was oxidized to give anti-9.
Removal of the TES group was accomplished using neutral fluoride ion (HF/TBAF)
[12] to give (þ)-(5R,6S)-1 without epimerization (98% ee and 96% de). The overall
yield was 47% from 3. The antipode (ꢀ)-ent-1 ((5S,6R)-1; 99% ee and 96% de) was
prepared from (R)-2.
Table. Alkylation of 12
Entry
Conditions
Yield [%]
1
2
3
4
PrMgBr (2.15 equiv.), THF, ꢀ 158
PrLi (6.5 equiv.), THF, ꢀ 788
42
37
83
58
PrLi (1.1 equiv.), Et2O, ꢀ 788
PrLi (1.3 equiv.), CeCl3 (1.3 equiv.), THF, ꢀ 788 [11]
2
)
Deprotection of the EE group of the corresponding compound 14 (pyridinium p-toluenesulfonate
(PPTS), MeOH) gave (þ)-1 with 70% de.
3
)
Direct conversion of thio ester 11 to ketone 14 failed under a variety of Fukuyama coupling
conditions and organocopper compounds.

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Helvetica Chimica Acta – Vol. 93 (2010)
Scheme 3. Synthesis of (þ)-(5R,6S)-1 and (ꢀ)-(5S,6R)-1 via Thiol Ester
a) TESOTf (1.2 equiv.), 2,6-lutidine (1.2 equiv.), CH2Cl2, ꢀ 558, 3 h. b) EtSH (3.8 equiv.), BuLi (2.6
equiv.), THF, ꢀ 78 to 78, 6 h. c) Diisobutylaluminum hydride (DIBAL; 1.01 equiv.), CH2Cl2, ꢀ 808,
20 min. d) PrLi (1.1 equiv.), Et2O, ꢀ 808, 30 min. e) IBX (4 equiv.), DMSO, r.t., 5 h. f) HF/TBAF (pH 7,
excess), THF/H2O, r.t., 2 h.
2.4. Synthesis of syn-Isomers via Thiol Esters. The synthetic pathway to the syn-
isomers, shown in Scheme 4, is similar to that of the anti-isomers. The syn-epimers of
pteroenone were more unstable and partially epimerized during the final purification
step (even with the use of neutral SiO2 for CC), and their diastereoisomeric purities
decreased to 90 – 91% de.
2.5. Fish Antifeedant Assay. The synthetic four diastereoisomers of pteroenone
showed no antifeedant activity against a benthic fish (Notothenia coriiceps) collected
near Palmer Station, Anvers Island, on the western Antarctic Peninsula. This indicates
that fish antifeedant bioactivity is not effective against all fish species, but rather if it
does exist in these compounds, it is likely to be targeted against ecologically relevant
species of fish such as those that are in sympatry with these pteropods in the Ross Sea,
Antarctica.
3. Conclusions. – Four stereoisomers of (þ)-pteroenone, a defensive metabolite of
the abducted Antarctic pteropod Clione antarctica, were synthesized by employing
anti-/syn-selective aldol reactions as the key step. The difference in reactivity and
stability between anti- and syn-aldol compounds was observed. syn-Isomers were rather
reactive and unstable. These compounds displayed no antifeedant activity against a
generally benthic Antarctic fish that does not co-occur with this pteropod, suggesting
that if they are deterrent they may be so only against sympatric, ecologically relevant,
fish predators.

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Scheme 4. Synthesis of syn-1 Isomers via Thiol Ester
a) TESOTf (1.2 equiv.), 2,6-lutidine (1.2 equiv.), CH2Cl2, ꢀ 558, 1.25 h. b) EtSH (6.9 equiv.), BuLi (4.6
equiv.), THF, ꢀ 78 to 78, 6 h. c) DIBAL (1.05 equiv.), CH2Cl2, ꢀ 808, 20 min. d) PrLi (2.6 equiv.), Et2O,
ꢀ 808, 30 min. e) 2-Iodoxybenzoic acid (IBX; 4.0 equiv.), DMSO, r.t., 7 h. f) HF/TBAF (pH 7, excess),
THF/H2O, 08, 0.5 h.
Experimental Part
General. TLC: Merck silica gel 60 F254 (0.25-mm thickness). Column chromatography (CC): Merck
silica gel 60 (SiO2; 70 – 230 mesh) and Kanto silica gel 60N (70 – 140 mesh, neutral). HPLC: Hitachi
L-6000 pump and a Hitachi L-4200 UV-VIS detector. M.p.: Yanaco MP-13; uncorrected. Optical
rotations: Horiba SEPA 300. IR: Jasco Report-100; in cmꢀ1. FT-IR: Jasco 4100 (ATR); in cmꢀ1. 1H- and
13C-NMR: Varian Gemini 2000 (300 MHz for 1H and 75 MHz for 13C), Varian Unity Inova 500 (500 MHz
for 1H and 125 MHz for 13C), and Varian Unity Inova 600 (150 MHz for 13C) rel. to Me4Si (¼0 ppm) in
CDCl3 unless otherwise noted; d in ppm, J in Hz. MS: Jeol JMS-700; using 3-nitrobenzyl alcohol
(NOBA) as a matrix (FAB); in m/z. Elemental analysis: Perkin-Elmer 2400II CHN.
(4S)-4-Benzyl-3-[(2R,3S,4E,6E)-3-hydroxy-2,4,6-trimethylocta-4,6-dienoyl]-1,3-oxazolidin-2-one
(anti-5). Aldehyde 3 [7] (434 mg, 3.49 mmol) was dissolved in AcOEt (2.8 ml) and added to acyl
oxazolidinone (S)-2 [6] (897 mg, 3.84 mmol). The mixture was then treated at r.t. with anh. MgCl2
(66.5 mg, 0.698 mmol), Et3N (97 ml, 6.99 mmol), and TMSCl (670 ml, 5.24 mmol). After stirring for 24 h,
the mixture was filtered through neutral SiO2 (AcOEt), and the filtrate was concentrated under reduced
pressure. The residual oil was dissolved in MeOH (5 ml), treated with CF3COOH (2 drops) and stirred
for 30 min. The mixture was concentrated under reduced pressure. Purification of crude product (89%
de) by CC (SiO2; hexane/AcOEt 6 :1 to 5 :1) and recrystallization from hexane/AcOEt afforded anti-5
(784 mg, 2.19 mmol, 63%). White needles. M.p. 105 – 1068. [a]2D4 ¼ þ120 (c ¼ 0.50, Et2O). Rf (hexane/
AcOEt 3 :1) 0.33. HPLC (column, Daicel Chiralcelꢀ OD, 4.6 ꢁ 250 mm; temp., 258; eluent, hexane/i-
PrOH 4 :1 at 0.5 ml/min; detection at 254 nm): tR 18.6 (> 99% de, > 99% ee). IR (KBr): 3450s (OH),
2950m, 1780s (C¼O), 1690s (C¼O), 1400s, 1000s. 1H-NMR (300 MHz): 7.22 – 7.37 (m, 5 arom. H); 5.92
(s, HꢀC(5’)); 5.45 (q, J ¼ 6.9, HꢀC(7’)); 4.66 – 4.75 (m, HꢀC(4)); 4.11 – 4.23 (m, CH2(5), HꢀC(3’),
HꢀC(2’)); 3.33 (dd, J ¼ 13.5, 3.6, 1 H, PhCH2); 2.78 (dd, J ¼ 13.5, 9.6, 1 H, PhCH2); 2.61 (d, J ¼ 6.3,

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Helvetica Chimica Acta – Vol. 93 (2010)
OH); 1.83 (s, MeꢀC(4’)); 1.75 (s, MeꢀC(6’)); 1.69 (d, J ¼ 7.2, Me(8’)); 1.09 (d, J ¼ 6.3, MeꢀC(2’)).
13C-NMR (150 MHz): 176.7; 153.8; 135.3; 133.3; 133.0; 132.9; 132.7; 129.5; 128.9; 127.3; 125.3; 125.29;
.
81.9; 66.0; 55.6; 40.7; 37.7; 16.5; 14.8; 13.7; 12.5. EI-MS: 357 (Mþ ), 339 ([M ꢀ H2O]þ), 233, 162, 135, 119,
.
91. HR-EI-MS: 357.1946 (Mþ , C21H27NO4þ ; calc. 357.1940). Anal. calc. for C21H27NO4: C 70.56, H 7.61, N
3.92; found: C 70.67, H 7.79, N 3.98.
(ꢀ)-(4R,2’S,3’R,4’E,6’E)-5 (ent-anti-5). In the same manner as described for anti-5, 3 (650 mg,
5.23 mmol) was converted to ent-anti-5 (1.18 g, 3.30 mmol, 63%). White needles. M.p. 105 – 1068 (hexane/
AcOEt). [a]2D4 ¼ ꢀ126 (c ¼ 0.230, Et2O). HPLC: tR 16.2 (> 98% de, > 99% ee). HR-FAB-MS: 380.1840
([M þ Na]þ, C21H27NNaOþ4 ; calc. 380.1838). Anal. calc. for C21H27NO4: C 70.56, H 7.61, N 3.92; found: C
70.57, H 7.81, N 3.99.
(2R,3S,4E,6E)-3-Hydroxy-N-methoxy-N,2,4,6-tetramethylocta-4,6-dienamide (anti-6) and (2S)-2-
{[(2R,3S,4E,6E)-3-Hydroxy-2,4,6-trimethylocta-4,6-dienoyl]amino}-3-phenylpropyl Methoxy(methyl)-
carbamate (7). To a soln. of MeONHMe · HCl (78 mg, 0.8 mmol) in dry CH2Cl2 (0.6 ml) was added a
soln. of Me3Al in hexane (1.0m, 0.8 ml, 0.8 mmol) at 08, and the mixture was stirred at 208 for 1 h under
N2. The soln. was cooled to ꢀ 208 before the addition of anti-5 (162 mg, 0.40 mmol) in dry CH2Cl2
(0.8 ml), and the mixture was stirred at 208 for 12 h. The reaction was quenched with sat. aq. Rochelleꢁs
salt soln. and extracted with CH2Cl2. The extract was washed with brine, dried (MgSO4), and
concentrated in vacuo. The residue was purified with prep. TLC (SiO2; hexane/AcOEt 2 :1) to give anti-6
(32 mg, 37%) and 7 (37%).
Data for anti-6. White needles. M.p. 58.5 – 59.5 (i-Pr2O). [a]2D6 ¼ þ6.7 (c ¼ 0.70, Et2O). Rf (hexane/
1
AcOEt 4 :1) 0.12. FT-IR: 1743s (C¼O), 1242m, 1025m, 702s. H-NMR (300 MHz): 5.90 (s, HꢀC(5));
5.41 (qt, J ¼ 6.4, 1.5, HꢀC(7)); 4.15 (pseudo-dd, J ¼ 7.6, 5.4, HꢀC(3)); 3.74 (s, MeO); 3.21 (s, MeN);
3.14 – 3.22 (m, HꢀC(2)); 2.89 (d, J ¼ 5.4, OH); 1.78 (d, J ¼ 1.2, MeꢀC(4)); 1.74 (s, MeꢀC(6)); 1.68 (d,
.
J ¼ 6.4, Me(8)); 1.09 (d, J ¼ 7.3, MeꢀC(2)). EI-MS: 241 (Mþ ), 224, 210, 135, 117. HR-EI-MS: 241.1680
.
(Mþ , C13H23NOþ3 ; calc. 241.1678).
Data for 7. White needles. M.p. 98 – 998. FT-IR: 3304m (NꢀH), 1739m, 1711m, 1644s (C¼O), 1548s,
1
1164s, 1006s, 753s, 701s. H-NMR (300 MHz): 7.20 – 7.36 (m, 5 arom. H); 6.18 (d, J ¼ 8.5, NH); 5.90 (s,
HꢀC(5)); 5.40 (qt, J ¼ 6.8, 1.5, HꢀC(7)); 4.41 – 4.53 (m, PhCH2CH); 4.18 (dd, J ¼ 11.3, 6.3, 1 H, CH2O);
4.13 (dd, J ¼ 11.3, 4.1, 1 H, CH2O); 4.00 (dd, J ¼ 7.8, 3.5, HꢀC(3)); 3.71 (s, MeO); 3.16 (s, MeN); 2.95
(dd, J ¼ 13.7, 6.0, 1 H, PhCH2); 2.82 (d, J ¼ 8.0, OH); 2.80 (dd, J ¼ 13.7, 8.0, 1 H, PhCH2); 2.37 (dq, 7.9, 7.1,
HꢀC(2)); 1.83 (d, J ¼ 1.1, MeꢀC(4)); 1.73 (s, MeꢀC(6)); 1.67 (d, J ¼ 6.9, HꢀC(8)); 1.03 (d, J ¼ 7.2,
MeꢀC(2)). FAB-MS: 441 ([M þ Na]þ), 419 ([M þ H]þ), 401 ([M þ H ꢀ H2O]þ). HR-FAB-MS:
419.2547 (Mþ, C23H35N2Oþ5 ; calc. 419.2546).
(2R,3S,4E,6E)-N-Methoxy-N,2,4,6-tetramethyl-3-[(triethylsilyl)oxy]octa-4,6-dienamide (anti-8). To
a soln. of anti-6 (33 mg, 0.14 mmol) in CH2Cl2 (0.5 ml) was successively added 2,6-lutidine (0.019 ml,
17 mg, 0.16 mmol) and TESOTf (0.034 ml, 40 mg, 0.15 mmol) at ꢀ 558, and the mixture was stirred for
12 h, while the temp. being raised to ꢀ 158. Then, the reaction was quenched with H2O. The aq. layer was
extracted with Et2O, and the combined org. layers were washed with brine, dried (MgSO4), filtered, and
concentrated. Purification of the crude product by CC (SiO2; hexane/AcOEt 6 :1) afforded anti-8
(41.0 mg, 0.12 mmol, 86%). Colorless oil. [a]2D6 ¼ þ16 (c ¼ 0.045, CHCl3). Rf (hexane/AcOEt 3 :1) 0.68.
FT-IR: 1664s (C¼O), 1064s, 1007s, 743s. 1H-NMR (500 MHz): 5.83 (s, HꢀC(5)); 5.39 (q, J ¼ 7.0,
HꢀC(7)); 4.16 (d, J ¼ 9.5, HꢀC(3)); 3.75 (s, MeO); 3.19 (s, MeN); 3.19 (overlapped m, HꢀC(2)); 1.74
(s, Me); 1.73 (s, Me); 1.69 (d, J ¼ 7.0, Me(8)); 0.97, 0.93, 0.89 (3t, J ¼ 8.0, (MeCH2)3Si); 0.87 (d, J ¼ 6.5,
.
MeꢀC(2)); 0.60, 0.53, 0.52 (3q, J ¼ 8.0, (MeCH2)3Si). EI-MS: 355 (Mþ ), 326 ([M ꢀ Et]þ), 295 ([M ꢀ
MeNOMe]þ), 262, 239 ([M ꢀ MeCHC(¼O)N(Me)OMe]þ), 200, 107, 91, 77. HR-EI-MS: 355, 2544
.
(Mþ , C19H37NO3Siþ; calc. 355.2543).
(5R,6S,7E,9E)-5,7,9-Trimethyl-6-[(triethylsilyl)oxy]undeca-7,9-dien-4-one (anti-9) from anti-8. To a
soln. of anti-8 (50 mg, 0.14 mmol) in THF (1 ml) was added PrLi in Et2O (1.28m, 0.33 ml, 0.42 mmol) at
ꢀ 708. After stirring for 18 h, the reaction was quenched with sat. aq. NH4Cl soln., and the mixture was
extracted with AcOEt. The org. layers were washed with brine, dried (MgSO4), filtered, and
concentrated. Purification of crude product by CC (SiO2; hexane/AcOEt 15 :1) afforded anti-9
(16 mg, 0.047 mmol, 34%). Colorless oil. The physical and spectral data: vide infra.

Helvetica Chimica Acta – Vol. 93 (2010)
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(4S)-4-Benzyl-3-{(2R,3S,4E,6E)-2,4,6-trimethyl-3-[(triethylsilyl)oxy]octa-4,6-dienoyl}-1,3-oxazoli-
din-2-one (anti-10). A ꢀ 558 soln. of anti-5 (200 mg, 0.559 mmol) in CH2Cl2 (3.5 ml) was treated with 2,6-
lutidine (78 ml, 72 mg, 0.67 mmol), followed by TESOTf (151 ml, 0.671mmol). After 80 min, the reaction
was quenched by H2O. The aq. layer was extracted with Et2O, and the combined org. layers were washed
with brine, dried (MgSO4), filtered, and concentrated. Purification of the crude product by CC (SiO2;
hexane/AcOEt 6 :1) afforded anti-10 (264 mg, 0.559 mmol, quant.). Colorless oil. Rf (hexane/AcOEt
3 :1) 0.53. [a]2D4 ¼ þ32 (c ¼ 1.2, Et2O). IR (film): 2950m, 1780s (C¼O), 1700s (C¼O), 1380s, 1220s,
1080s, 740s. 1H-NMR (300 MHz): 7.25 – 7.38 (m, 5 arom. H); 5.86 (s, HꢀC(5’)); 5.42 (q, J ¼ 6.9,
HꢀC(7’)); 4.65 – 4.74 (m, HꢀC(4)); 4.35 (d, HꢀC(3’)) 4.08 – 4.21 (m, CH2(5), HꢀC(2’)); 3.39 (dd, J ¼
13.2, 3.3, 1 H, PhCH2); 2.70 (dd, J ¼ 13.2, 9.9, 1 H, PhCH2); 1.78 (d, J ¼ 0.9, MeꢀC(4’)); 1.75 (s,
MeꢀC(6’)); 1.70 (d, J ¼ 6.9, Me(8’)); 0.97 (d, J ¼ 7.2, MeꢀC(2’)); 0.931 (t, J ¼ 7.8, (MeCH2)3Si); 0.57 (q,
J ¼ 7.8, (MeCH2)3Si). 13C-NMR (150 MHz): 176.3; 153.1; 135.6; 134.1; 133.0; 132.8; 129.4; 128.9; 127.2;
.
124.8; 82.2; 65.6; 55.3; 41.8; 38.0; 22.6; 16.4; 14.6; 13.6; 12.2; 6.89; 6.38; 4.80. EI-MS: 471 (Mþ ), 442
.
([M ꢀ Et]þ), 339 ([M ꢀ TESOH]þ), 318, 294, 262, 239, 115, 87. HR-EI-MS: 471.2811 (Mþ
,
C27H41NO4Siþ; calc. 471.2804).
(4R,2’S,3’R,4’E,6’E)-Isomer (ent-anti-10). In the same manner as described for anti-10, ent-anti-5
(633 mg, 1.77 mmol) afforded ent-anti-10 (835 mg, 1.77 mmol, quant.). Colorless oil. [a]2D4 ¼ ꢀ29 (c ¼
0.18, Et2O). HR-FAB-MS: 494.2706 ([M þ Na]þ, C27H41NNaO4Siþ; calc. 494.2702).
S-Ethyl (2R,3S,4E,6E)-2,4,6-Trimethyl-3-[(triethylsilyl)oxy]octa-4,6-dienethioate (anti-11). To a
soln. of EtSH (99 ml, 1.3 mmol) in THF (5 ml) was added dropwise BuLi in hexane (1.6m, 0.56 ml,
0.89 mmol) at ꢀ 788 under Ar, and the mixture was stirred for 25 min. Then, to the mixture was added a
soln. of anti-10 (164 mg, 0.35 mmol) in THF (2 ml). The mixture was gradually warmed to 08, and the
reaction was quenched with sat. aq. NaHCO3 soln., and the resulting mixture was extracted with Et2O.
The combined extract was washed with brine, dried (MgSO4), and concentrated in vacuo. It was
chromatographed on SiO2. Elution with (hexane/AcOEt 10 :1) gave anti-11 (123 mg, 0.35 mmol, quant.).
Colorless oil. [a]D24 ¼ ꢀ11 (c ¼ 0.36, Et2O). Rf (hexane/AcOEt 6 :1) 0.67. IR (film): 2950m, 2900s, 1690s
1
(C¼O), 1460s (C¼O), 1240s, 1070s, 1000s, 960s, 740s. H-NMR (300 MHz): 5.80 (s, HꢀC(5)); 5.38 (q,
J ¼ 6.6, HꢀC(7)); 4.17 (d, J ¼ 9.6, HꢀC(3)); 2.87 (q, J ¼ 7.5, MeCH2S); 2.81 (dq, J ¼ 9.6, 6.9, HꢀC(2));
1.72 (s, MeꢀC(4)); 1.69 (s, MeꢀC(6)); 1.68 (d, J ¼ 6.6, Me(8)); 1.25 (t, J ¼ 7.5, MeCH2S); 0.91 (d, J ¼ 6.9,
MeꢀC(2)); 0.90 (t, J ¼ 7.8, (MeCH2)3Si); 0.53 (q, J ¼ 7.8, (MeCH2)3Si). 13C-NMR (150 MHz): 202.9;
.
133.9; 132.8; 132.6; 124.6; 81.7; 53.1; 23.2; 16.4; 15.0; 14.6; 13.6; 11.9; 6.79; 6.38; 4.68. EI-MS: 356 (Mþ ),
.
327 ([M ꢀ Et]þ), 239. HR-EI-MS: 356.2202 (Mþ , C19H36O2SSiþ; calc. 356.2205).
(2S,3R,4E,6E)-Isomer (ent-anti-11). In the same manner as described for anti-11, ent-anti-10
(888 mg, 1.88 mmol) afforded ent-anti-11 (638 mg, 1.79 mmol, 95%). Colorless oil. [a]2D4 ¼ þ14 (c ¼ 1.0,
Et2O). HR-FAB-MS: 357.2286 ([M þ H]þ, C19H37O2SiSþ; calc. 357.2284).
(2R,3S,4E,6E)-2,4,6-Trimethyl-3-[(triethylsilyl)oxy]octa-4,6-dienal (anti-12). A flask was charged
with anti-11 (47 mg, 0.1318 mmol) in dry CH2Cl2 (0.75 ml) at ꢀ 808. To the soln. was added DIBAL in
hexane (0.94m, 266 ml, 0.283 mmol). After 50 min, the mixture was stirred with aq. Rochelle salt soln.,
then extracted with Et2O. The combined extract was washed with brine, dried (MgSO4), and
concentrated in vacuo to give anti-12 in an almost quant. yield. Colorless oil. [a]2D4 ¼ þ10 (c ¼ 1.95,
Et2O). Rf (hexane/AcOEt 6 :1) 0.43. IR (film): 2950m, 2855s, 1725s (C¼O), 1060s. 1H-NMR (300 MHz):
9.78 (d, J ¼ 2.7, HꢀC(1)); 5.82 (s, HꢀC(5)); 5.40 (q, J ¼ 6.9, HꢀC(7)); 4.08 (d, J ¼ 8.7, HꢀC(3)); 2.54 –
2.65 (m, HꢀC(2)); 1.73 (s, MeꢀC(4)); 1.70 (s, MeꢀC(6)); 1.68 (d, J ¼ 6.9, Me(8)); 0.90 (t, J ¼ 8.4,
(MeCH2)3Si); 0.88 (d, J ¼ 6.9, MeꢀC(2)); 0.57 (q, J ¼ 8.4, (MeCH2)3Si). 13C-NMR (150 MHz): 205.5;
.
133.6; 132.7; 132.3; 124.9; 80.9; 50.2; 23.0; 16.4; 13.7; 12.4; 11.0; 6.79; 4.76. EI-MS: 296 (Mþ ), 267 ([M ꢀ
.
Et]þ), 239, 217, 115 ([Et3Si]þ), 87. HR-EI-MS: 296.2174 (Mþ , C17H32O2Siþ; calc. 296.2172).
(4RS,5R,6S,7E,9E)-5,7,9-Trimethyl-6-[(triethylsilyl)oxy]undeca-7,9-dien-4-ol (anti-13). To a soln. of
anti-12 (22 mg, 0.0742 mmol) in Et2O (0.5 ml) was added PrLi in Et2O (1.3m, 63 ml, 0.0816 mmol) at
ꢀ 808 under Ar, and the mixture was stirred for 30 min. The reaction was quenched with sat. aq. NH4Cl
soln., and the resulting mixture was extracted with Et2O. The combined extract was washed with brine,
dried (MgSO4), and concentrated in vacuo. Purification of the crude product by TLC (hexane/AcOEt
15 :1) afforded anti-13 (21 mg, 0.062 mmol, 83%). Colorless oil. Rf (hexane/AcOEt 6 :1) 0.52. IR (film):
3450s (br., OH), 2900s, 1450s, 1050s. 1H-NMR (300 MHz): 5.91 (s, HꢀC(8)); 5.36 (q, J ¼ 6.6, HꢀC(10));

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Helvetica Chimica Acta – Vol. 93 (2010)
4.04 (d, J ¼ 5.1, HꢀC(6)); 3.84 – 3.92 (m, HꢀC(4)); 3.13 (d, J ¼ 3.6, OH); 1.73 (s, MeꢀC(7)); 1.69 (d,
J ¼ 6.0, Me(11)); 1.68 (s, MeꢀC(9)); 1.43 – 1.52 (m, CH2(3), HꢀC(5)); 1.24 – 1.34 (m, CH2(2)); 0.96 (t,
J ¼ 7.2, (MeCH2)3Si); 0.92 (t, J ¼ 6.9, Me(1)); 0.88 (d, J ¼ 7.2, MeꢀC(5)); 0.62 (q, J ¼ 7.2, (MeCH2)3Si).
13C-NMR (150 MHz): 134.4; 133.0; 130.3; 124.0; 82.9; 71.0; 65.8; 39.3; 36.3; 19.5; 16.6; 15.3; 14.4; 14.1;
13.6; 11.5; 6.85; 4.74. FAB-MS: 363 ([M þ H]þ), 239, 209, 137, 109, 87. HR-FAB-MS: 363.2698 ([M þ
Na]þ, C20H40NaO2Siþ; calc. 363.2695).
(4RS,5S,6R,7E,9E)-Isomer (ent-anti-13). In the same manner as described for anti-13, ent-anti-12
(618 mg, 1.73 mmol) afforded ent-anti-13 (246 mg, 0.71 mmol, 42% in two steps). Colorless oil. HR-FAB-
MS: 363.2701 ([M þ Na]þ, C20H40NaO2Siþ; calc. 363.2695).
Compound anti-9 from anti-13. To a soln. of anti-13 (21 mg, 0.062 mmol) in DMSO (1 ml) at r.t. were
added IBX (69 mg, 0.2467 mmol) and mol. sieves (4 ꢄ; 130 mg). After stirring for 5 h, the reaction was
quenched with ice-cold H2O, and the mixture was stirred for 10 min. It was filtered out Celite pad and
extracted with AcOEt. The org. layer were washed with brine, dried (MgSO4), filtered, and
concentrated. Purification of crude product by CC (SiO2; hexane/AcOEt 15 :1) afforded anti-9
(20 mg, 0.059 mmol, 96%). Colorless oil. [a]2D4 ¼ þ16 (c ¼ 0.40, Et2O). Rf (hexane/AcOEt 6 :1) 0.67. IR
(film): 3300s, 2950s, 1650s (C¼O), 1060s. 1H-NMR (300 MHz): 5.79 (s, HꢀC(8)); 5.38 (q, J ¼ 6.6,
HꢀC(10)); 4.06 (d, J ¼ 9.6, HꢀC(6)); 2.79 (dq, J ¼ 7.2, 9.6, HꢀC(5)) 2.46 – 2.54 (m, CH2(3)); 1.72 (s,
MeꢀC(7)); 1.70 (s, MeꢀC(9)); 1.68 (d, J ¼ 7.8, Me(11)); 1.58 (m, CH2(2)); 1.21 (d, J ¼ 7.2, Me(1)); 0.88
(t, J ¼ 7.5, (MeCH2)3Si); 0.79 (d, J ¼ 7.2, MeꢀC(5)); 0.51 (q, J ¼ 7.5, (MeCH2)3Si). 13C-NMR
(150 MHz): 214.4; 133.9; 132.6; 132.3; 124.5; 82.4; 49.1; 46.7; 22.6; 16.4; 16.2; 13.6; 13.5; 13.4; 11.8;
6.60; 4.47. FAB-MS: 361 ([M þ Na]þ), 309, 239, 209, 185, 115 ([Et3Si]þ), 87. HR-FAB-MS: 361.2542
([M þ Na]þ, C20H38NaO2Siþ; calc. 361.2538).
(5S,6R,7E,9E)-Isomer (ent-anti-9). In the same manner as described for anti-9, ent-anti-13 (124 mg,
0.363 mmol) afforded ent-anti-9 (123 mg, 0.363 mmol, quant.). Colorless oil. [a]2D4 ¼ ꢀ13 (c ¼ 0.11,
Et2O). HR-FAB-MS: 361.2541 ([M þ Na]þ, C20H38NaO2Siþ; calc. 361.2538).
Pteroenone (¼(5R,6S,7E,9E)-6-Hydroxy-5,7,9-trimethylundeca-7,9-dien-4-one; (þ)-(5R,6S)-1). A
soln. of anti-9 (13 mg, 0.0384 mmol) in THF (0.5 ml) was added dropwise to a soln. TBAF/HF (pH 7;
prepared by mixing 1m TBAF in THFand 47% aq. HF) at 08. After stirring for 2 h at r.t., the mixture was
poured into brine and extracted with AcOEt. The extract was washed with brine, dried (MgSO4), and
concentrated in vacuo. The residue was chromatographed (SiO2; hexane/AcOEt 15 :1) to give (þ)-
(5R,6S)-1 (8 mg, 0.0357 mmol, 93%). Colorless oil. [a]2D4 ¼ þ47 (c ¼ 0.30, hexane; [2]: [a]D ¼ þ48 (c ¼
0.6, hexane)). Rf (hexane/AcOEt 4 :1) 0.41. HPLC (column, Daicel Chiralcelꢀ OJ, 4.6 ꢁ 250 mm; temp.,
258; eluent, hexane/i-PrOH 100 :1 at 0.5 ml/min; detection at 234 nm): tR 24.7 (98% ee, 96% de).
1H-NMR (500 MHz, C6D6): 5.78 (s, HꢀC(8)); 5.40 (q, J ¼ 6.7, HꢀC(10)); 4.07 (dd, J ¼ 2.5, 9.0, HꢀC(6));
2.60 (qd, J ¼ 7.0, 9.5, HꢀC(5)); 2.31 (td, J ¼ 7.3, 17.5, 1 H, CH2(3)); 2.19 (td, J ¼ 7.3, 17.5, 1 H, CH2(3));
1.71 (s, MeꢀC(7)); 1.67 (d, J ¼ 3.5, OH); 1.65 (s, MeꢀC(9)); 1.62 (sext., J ¼ 7.5, CH2(9)); 1.58 (d, J ¼ 7.0,
Me(11)); 0.84 (t, J ¼ 7.5, Me(1)); 0.82 (3 H, d, J ¼ 7.5, MeꢀC(5)). 1H-NMR (500 MHz, CDCl3): 5.87 (s,
HꢀC(8)); 5.42 (q, J ¼ 6.6, HꢀC(10)); 4.13 (dd, J ¼ 3.3, 8.7, HꢀC(6)); 2.80 (dq, J ¼ 7.2, 8.8, HꢀC(5))
2.51 (t, J ¼ 7.2, CH2(3)); 1.76 (s, MeꢀC(7)); 1.74 (s, MeꢀC(9)); 1.68 (d, J ¼ 6.6, Me(11)); 1.62 (sext., J ¼
7.3, CH2(2)); 0.95 (d, J ¼ 8.8, MeꢀC(5)); 0.92 (d, J ¼ 7.2, HꢀC(1)). 13C-NMR (150 MHz, C6D6): 12.5
(MeꢀC(7)); 13.7 (C(1)); 13.9 (C(11)); 14.1 (MeꢀC(5)); 16.5 (MeꢀC(9)); 17.0 (C(2)); 45.6 (C(3)); 48.8
(C(5)); 81.3 (C(6)); 124.9 (C(10)); 132.4 (C(8)); 133.2 (C(9)); 134.5 (C(7)); 213.2 (C(4)). FAB-MS: 247
.
([M þ Na]þ), 207 ([M þ H ꢀ H2O]þ), 195, 173, 115, 93, 81. HR-EI-MS: 224.1777 (Mþ , C14H24Oþ2 ; calc.
224.1776).
(5S,6R,7E,9E)-6-Hydroxy-5,7,9-trimethylundeca-7,9-dien-4-one ((ꢀ)-(5S,6R)-1). In the same man-
ner as described for (5R,6S)-1, ent-anti-9 (18.6 mg, 0.0549 mmol) afforded (5S,6R)-1 (12.3 mg,
0.0549 mmol, quant.). Colorless oil. [a]2D4 ¼ ꢀ46 (c ¼ 0.13, hexane). HPLC (column, Daicel Chiralcelꢀ
OJ, 4.6 ꢁ 250 mm; temp., 258; eluent, hexane/i-PrOH 100 :1 at 0.5 ml/min; detection at 234 nm): tR 22.6
.
(99% ee, 96% de). HR-EI-MS: 224.1674 (Mþ , C14H24O2þ ; calc. 224.1776).
(4S)-4-Benzyl-3-[(2S,3S,4E,6E)-3-hydroxy-2,4,6-trimethylocta-4,6-dienoyl]-1,3-oxazolidin-2-one
(syn-5). To a soln. of (S)-2 (789 mg, 3.38 mmol) in 10 ml of CH2Cl2 at 08 under N2 was added Bu2BOTf
(3.7 ml, 3.7 mmol), followed by Et3N (0.54 ml, 3.86 mmol). The mixture was cooled to ꢀ 788 and 3
(400 mg, 3.22 mmol) was added. The mixture was stirred for 30 min at this temp. and gradually warmed to

Helvetica Chimica Acta – Vol. 93 (2010)
1941
08. After 6 h, the reaction was quenched by the addition of 20 ml of phosphate buffer (pH 7)/MeOH 1:1,
followed by addition of 20 ml of 30% aq. H2O2/MeOH 1:1, and the mixture was stirred vigorously for
1 h. The mixture was evaporated to remove MeOH and extracted twice with CH2Cl2, and the combined
org. layers were washed with brine, and dried (MgSO4). It was filtered and concentrated under reduced
pressure. Purification of crude product by CC (SiO2; hexane/AcOEt 6 :1 to 3 :1) afforded syn-5 (862 mg,
2.41 mmol, 75%). Colorless oil. [a]2D4 ¼ þ73 (c ¼ 0.50, Et2O). Rf (hexane/AcOEt 3 :1) 0.33. HPLC
(column, Daicel Chiralcel ꢀOD, 4.6 ꢁ 250 mm; temp., 258; eluent, hexane/i-PrOH 4 :1 at 0.5 ml/min;
detection at 254 nm): tR 17.7 (> 99% dr). IR (KBr): 3500s (OH), 2900m, 1780s (C¼O), 1700s (C¼O),
1390s, 1210s. 1H-NMR (300 MHz): 7.20 – 7.37 (m, 5 arom. H); 6.02 (s, HꢀC(5’)); 5.40 (q, J ¼ 6.9,
HꢀC(7’)); 4.65 – 4.74 (m, HꢀC(4)); 4.36 – 4.40 (m, HꢀC(3’)); 4.16 – 4.22 (m, CH2(5)); 4.02 (dq, J ¼ 7.2,
3.9, HꢀC(2’)); 3.28 (dd, J ¼ 13.5, 3.3, 1 H, PhCH2); 2.80 (dd, J ¼ 13.5, 9.6, 1 H, PhCH2); 2.78 (d, J ¼ 3.0,
OH); 1.75 (s, MeꢀC(4’)); 1.74 (s, MeꢀC(6’)); 1.68 (d, J ¼ 6.6, Me(8’)); 1.21 (d, J ¼ 7.2, MeꢀC(2’)). EI-
.
.
MS: 357 (Mþ ), 339 ([M ꢀ H2O]þ), 233, 177, 91. HR-EI-MS: 357.1938 (Mþ , C21H27NOþ4 ; calc. 357.1940).
(4R,2’R,3’R,4’E,6’E)-5 (ent-syn-5). In the same manner as described for syn-5, 3 (463 mg,
3.73 mmol) afforded ent-syn-5 (1.08 g, 3.02 mmol, 85%). Colorless oil. [a]2D4 ¼ ꢀ74 (c ¼ 0.24, Et2O).
HPLC: tR 16.5 (> 99% dr). HR-FAB-MS: 380.1838 ([M þ Na]þ, C21H27NNaO4þ ; calc. 380.1838). Anal.
calc. for C21H27NO4: C 70.57, H 7.88, N 3.84; found: C 70.57, H 7.81, N 3.99.
(2S,3S,4E,6E)-3-Hydroxy-N-methoxy-N,2,4,6-tetramethylocta-4,6-dienamide (syn-6). To a suspen-
sion of MeONHMe · HCl (205 mg, 2.10 mmol) in dry THF (1.6 ml) was added a soln. of Me3Al in hexane
(1.0m, 2.1 ml, 2.1 mmol) at 08, and the mixture was stirred at 208 for 15 min under N2. The soln. was
cooled to ꢀ 208 before the addition of 5 (250 mg, 0.699 mmol) in dry THF (1.7 ml), and the mixture was
stirred at 208 for 9 h. The reaction was quenched with 0.5m aq. HCl, and the mixture was extracted with
CH2Cl2. The extract was washed with sat. aq. NaHCO3 soln. and brine, dried (MgSO4) and concentrated
in vacuo. The residue was purified with prep. TLC (SiO2; hexane/AcOEt 4 :1) to give syn-6 (138 mg,
0.572 mmol, 82%). Colorless oil. [a]2D6 ¼ ꢀ19 (c ¼ 0.29, CHCl3). Rf (toluene/AcOEt 3 :1) 0.40. FT-IR:
3400s (br., OH), 1738s (C¼O), 1641s, 1071m, 1003s, 741s. 1H-NMR (600 MHz): 6.06 (s, 0.8 H of
HꢀC(5)); 6.04 (s, 0.2 H of HꢀC(5)); 5.39 (q, J ¼ 6.7, 0.8 H of HꢀC(7)); 5.33 (q, J ¼ 6.5, 0.2 H of
HꢀC(7)); 4.35 (s, 0.2 H); 4.29 (s, 0.8 H); 4.00 (s, 0.2 H); 3.93 (s, 0.8 H); 3.73 (s, 0.6 H of MeO); 3.72 (s,
2.4 H of MeO); 3.21 (s, 2.4 H of MeN); 3.11 (s, 0.6 H of MeN); 1.74 (s, Me); 1.73 (s, 2.4 H of Me); 1.68 (d,
J ¼ 6.6, 2.4 H of Me(8)); 1.55 (s, 0.6 H of Me); 1.51 (d, J ¼ 6.6, 0.6 H of Me(8)); 1.15 (d, J ¼ 7.1, 0.6 H of
.
MeꢀC(2)); 1.11 (d, J ¼ 7.0, 2.4 H of MeꢀC(2)). EI-MS: 241 (Mþ ), 224, 135, 117. HR-EI-MS: 241.1679
.
(Mþ , C13H23NOþ3 ; calc. 241.1678).
(2S,3S,4E,6E)-N-Methoxy-N,2,4,6-tetramethyl-3-[(triethylsilyl)oxy]octa-4,6-dienamide (syn-8). To a
soln. of syn-6 (34 mg, 0.14 mmol) in CH2Cl2 (0.5 ml) was successively added 2,6-lutidine (0.020 ml, 18 mg,
0.17 mmol) and TESOTf (0.035 ml, 40 mg, 0.16 mmol) at ꢀ 308, and the mixture was stirred for 12 h. The
reaction was quenched with H2O. The aq. layer was extracted with Et2O, and the combined org. layers
were washed with brine, dried (MgSO4), filtered, and concentrated. Purification of the crude product by
CC (SiO2; hexane/AcOEt 10 :1) afforded syn-8 (39 mg, 0.11 mmol, 79%). Colorless oil. [a]2D6 ¼ þ17 (c ¼
1
0.71, CHCl3). Rf (hexane/AcOEt 2 :1) 0.56. FT-IR: 1664s (C¼O), 1411m, 1063s, 996s, 726s. H-NMR
(500 MHz): 5.75 (s, HꢀC(5)); 5.30 (q, J ¼ 6.6, HꢀC(7)); 4.25 (d, J ¼ 9.1, 0.2 H of HꢀC(3)); 4.13 (d, J ¼
9.1, 0.8 H of HꢀC(3)); 3.65 (s, 0.6 H of MeO); 3.64 (s, 2.4 H of MeO); 3.19 (br. s, HꢀC(2)); 3.10 (s,
MeN); 1.73 (s, 2.4 H of Me); 1.68 (s, 0.6 H of Me); 1.66 (s, Me); 1.65 (d, J ¼ 6.6, Me(8)); 1.22 (d, J ¼ 6.8,
0.6 H of MeꢀC(2)); 1.21 (d, J ¼ 6.8, 2.4 H of MeꢀC(2)); 0.96 (t, J ¼ 8.1, 1.8 H of (MeCH2)3Si); 0.95 (t,
J ¼ 8.1, 7.2 H of (MeCH2)3Si); 0.62 (q, J ¼ 8.1, 1.2 H of (MeCH2)3Si); 0.60 (q, J ¼ 8.1, 4.8 H of
.
(MeCH2)3Si). EI-MS: 355 (Mþ ), 326 ([M ꢀ Et]þ), 295 ([M ꢀ NMeOMe]þ), 239 ([M ꢀ
.
MeCHC(¼O)NMeOMe]þ), 115, 87. HR-EI-MS: 355.2543 (Mþ , C19H37NO3Siþ; calc. 355.2543).
(4S)-4-Benzyl-3-{(2S,3S,4E,6E)-2,4,6-trimethyl-3-[(triethylsilyl)oxy]octa-4,6-dienoyl}-1,3-oxazoli-
din-2-one (syn-10). A soln. of syn-5 (400 mg, 1.12 mmol) at ꢀ 558 in CH2Cl2 (7 ml) was treated with 2,6-
lutidine (156 ml), followed by TESOTf (303 ml, 1.34 mmol). After 75 min, the reaction was quenched by
H2O. The aq. layer was extracted with Et2O, and the combined org. layers were washed with brine, dried
(MgSO4), filtered, and concentrated. Purification of the crude product by CC (SiO2; hexane/AcOEt 6 :1)
afforded syn-10 (418 mg, 0.886 mmol, 79%). Colorless oil. [a]2D4 ¼ þ64 (c ¼ 2.0, Et2O). Rf (hexane/
1
AcOEt 3 :1) 0.62. IR (film): 2950m, 1780s (C¼O), 1700s (C¼O), 1380s, 1210s, 1080s, 740s. H-NMR

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Helvetica Chimica Acta – Vol. 93 (2010)
(300 MHz): 7.20 – 7.37 (m, 5 arom. H); 5.79 (s, HꢀC(5’)); 5.32 (q, J ¼ 6.6, HꢀC(7’)); 4.51 (dddd, J ¼ 9.6,
7.5, 3.3, 2.4, HꢀC(4)); 4.24 (d, J ¼ 7.8, HꢀC(3’)); 4.03 – 4.15 (m, CH2(5), HꢀC(2’)); 3.27 (dd, J ¼ 13.2,
3.3, 1 H, PhCH2); 2.75 (dd, J ¼ 13.2, 9.9, 1 H, PhCH2); 1.73 (d, J ¼ 1.2, MeꢀC(4’)); 1.69 (s, MeꢀC(6’));
1.65 (d, J ¼ 6.9, Me(8’)); 1.24 (d, J ¼ 6.9, MeꢀC(2’)); 0.94 (t, J ¼ 8.1, (MeCH2)3Si); 0.58 (q, J ¼ 8.1,
.
(MeCH2)3Si). EI-MS: 471 (Mþ ), 442 ([M ꢀ Et]þ), 339 ([M ꢀ TESOH]þ), 318, 294, 262 239, 200, 115, 91.
.
HR-EI-MS: 471.2805 (Mþ , C27H41NO4Siþ; calc. 471.2804).
(4R,2’R,3’R,4’E,6’E)-Isomer (ent-syn-10). In the same manner as described for syn-10, ent-syn-5
(730 mg, 2.04 mmol) afforded ent-syn-10 (962 mg, 2.04 mmol, quant.). Colorless oil. [a]2D4 ¼ ꢀ59 (c ¼
0.55, Et2O). HR-FAB-MS: 494.2709 ([M þ Na]þ, C27H41NNaO4Siþ; calc. 494.2702).
S-Ethyl (2S,3S,4E,6E)-2,4,6-Trimethyl-3-[(triethylsilyl)oxy]octa-4,6-dienethioate (syn-11). To a soln.
of EtSH (179 ml, 2.42 mmol) in THF (9 ml) was added dropwise BuLi in hexane (1.6m, 1.0 ml,
1.615 mmol) at ꢀ 788 under Ar, and the mixture was stirred for 15 min. Then, to the mixture was added a
soln. of syn-10 (164 mg, 0.35 mmol) in THF (2 ml). The mixture was gradually warmed to 08 and stirred
with sat. aq. NaHCO3 soln., and the resulting mixture was extracted with Et2O. The combined extract was
washed with brine, dried (MgSO4), and concentrated in vacuo. CC (SiO2; hexane/AcOEt 10 :1) gave syn-
11 (288 mg, 0.808 mmol, quant.). Colorless oil. [a]2D4 ¼ þ47 (c ¼ 0.43, Et2O). Rf (hexane/AcOEt 6 :1)
0.61. IR (film): 2950m, 2875s, 1680s (C¼O), 1460s (C¼O), 1240s, 1080s, 1000s, 960s, 740s. 1H-NMR
(300 MHz): 5.74 (s, HꢀC(5)); 5.33 (q, J ¼ 6.6, HꢀC(7)); 4.15 (d, J ¼ 7.2, HꢀC(3)); 2.77 – 2.88 (m,
MeCH2S); 2.72 (dq, J ¼ 9.0, 7.5, HꢀC(2)); 1.74 (s, MeꢀC(4)); 1.67 (s, MeꢀC(6)); 1.66 (d, J ¼ 9.9,
Me(8)); 1.20 (d, J ¼ 7.2, MeꢀC(2)); 1.19 (t, J ¼ 7.2, MeCH2S); 0.93 (t, J ¼ 7.8, (MeCH2)3Si); 0.57 (q, J ¼
7.8, (MeCH2)3Si). 13C-NMR (150 MHz): 201.8; 134.3; 132.8; 131.4; 124.2; 80.4; 53.5; 23.0; 16.4; 14.6;
.
13.7; 13.6; 13.0; 6.83; 6.79; 6.38; 4.77. EI-MS: 356 (Mþ ), 327 ([M ꢀ Et]þ), 291, 239, 217, 189, 161, 133, 115
.
([Et3Si]þ), 87. HR-EI-MS: 356.2207 (Mþ , C19H36O2SSiþ; calc. 356.2205).
(2R,3R,4E,6E)-Isomer (ent-syn-11). In the same manner as described for syn-11, ent-syn-10 (681 mg,
1.44 mmol) afforded ent-syn-11 (514 mg, 1.44 mmol, quant.). Colorless oil. [a]2D4 ¼ ꢀ44 (c ¼ 0.25, Et2O).
HR-FAB-MS: 357.2288 ([M þ H]þ, C19H37O2SSiþ; calc. 357.2284).
(2S,3S,4E,6E)-2,4,6-Trimethyl-3-[(triethylsilyl)oxy]octa-4,6-dienal (syn-12). A flask was charged
with syn-11 (90 mg, 0.252 mmol) in dry CH2Cl2 (1.5 ml) at ꢀ 808. To the soln. was added DIBAL in
hexane (0.94m, 0.28 ml, 0.265 mmol). After 20 min, the mixture was stirred with aq. Rochelle salt soln.,
then extracted with Et2O. The combined extract was washed with brine, dried (MgSO4), and
concentrated in vacuo to give syn-12 (74 mg, 0.250 mmol, 99%). Colorless oil. [a]2D4 ¼ ꢀ8.0 (c ¼ 1.0,
Et2O). Rf (hexane/AcOEt 6 :1) 0.52. IR (film): 2950m, 2855s, 1725s (C¼O), 1060s. 1H-NMR (300 MHz):
9.69 (d, J ¼ 2.1, HꢀC(1)); 5.87 (s, HꢀC(5)); 5.36 (q, J ¼ 6.9, HꢀC(7)); 4.31 (d, J ¼ 6.6, HꢀC(3)); 2.54
(quint., J ¼ 6.9, HꢀC(2)); 1.72 (s, MeꢀC(4)); 1.72 (s, MeꢀC(6)); 1.68 (d, J ¼ 6.9, Me(8)); 1.05 (d, J ¼
6.9, Meꢀ(2)); 0.94 (t, J ¼ 8.4, (MeCH2)3Si); 0.58 (q, J ¼ 7.5, (MeCH2)3Si). 13C-NMR (150 MHz): 204.7;
.
133.9; 132.7; 130.9; 124.6; 78.1; 51.0; 23.0; 16.5; 14.1; 13.6; 8.96; 6.80; 4.77. EI-MS: 296 (Mþ ), 267 ([M ꢀ
.
Et]þ), 239, 217, 115 ([Et3Si]þ), 87. HR-EI-MS: 296.2178 (Mþ , C17H32O2Siþ; calc. 296.2172).
(4RS,5R,6S,7E,9E)-5,7,9-Trimethyl-6-[(triethylsilyl)oxy]undeca-7,9-dien-4-ol (syn-13). To a soln. of
syn-12 (31 mg, 0.10 mmol) in Et2O (1.0 ml) was added PrLi in Et2O (1.3m, 160 ml, 0.273 mmol) at ꢀ 808
under Ar, and the mixture was stirred for 30 min. The reaction was quenched with sat. aq. NH4Cl soln.,
and the resulting mixture was extracted with Et2O. The combined extract was washed with brine, dried
(MgSO4), and concentrated in vacuo. Purification of the crude product by TLC (hexane/AcOEt 50 :1)
afforded syn-13 (22 mg, 0.065 mmol, 65%). Colorless oil. Rf (hexane/AcOEt 6 :1) 0.54. IR (film): 3450s
(br., OH), 2880s, 1460s, 1000s. 1H-NMR (300 MHz): 5.85 (s, HꢀC(8)); 5.36 (q, J ¼ 6.9, HꢀC(10)); 4.05
(d, J ¼ 6.3, HꢀC(6)); 3.50 – 3.60 (m, HꢀC(4)) 2.13 (d, J ¼ 3.3, OH); 1.73 (s, MeꢀC(7)); 1.69 (d, J ¼ 6.9,
Me(11)); 1.69 (s, MeꢀC(9)); 1.26 – 1.54 (m, CH2(3), CH2(2), HꢀC(5)); 0.95 (t, J ¼ 7.8, (MeCH2)3Si);
0.95 (t, J ¼ 7.8, Me(1)); 0.88 (d, J ¼ 6.9, MeꢀC(5)); 0.62 (q, J ¼ 7.8, (MeCH2)3Si). 13C-NMR (150 MHz):
135.2; 133.0; 130.2; 124.1; 82.4; 73.2; 65.8; 40.7; 37.4; 19.3; 16.6; 15.3; 14.2; 14.1; 13.6; 7.01; 6.87; 4.85. FAB-
MS: 339 ([M ꢀ H]ꢀ), 306, 199, 153, 131. HR-FAB-MS: 339.2719 ([M ꢀ H]ꢀ, C20H39O2Siꢀ; calc.
339.2719).
(4RS,5R,6S,7E,9E)-Isomer (ent-syn-13). In the same manner as described for syn-12 and syn-13, ent-
syn-11 (489 mg, 1.37 mmol) afforded ent-syn-13 (233 mg, 0.685 mmol, 50% in two steps). Colorless oil.
HR-FAB-MS: 363.2697 ([M þ Na]þ, C20H40NaO2Siþ; calc. 363.2695).

Helvetica Chimica Acta – Vol. 93 (2010)
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(5S,6S,7E,9E)-5,7,9-Trimethyl-6-[(triethylsilyl)oxy]undeca-7,9-dien-4-one (syn-9). To a soln. of syn-
13 (18 mg, 0.0528 mmol) in DMSO (1 ml) at r.t. were added IBX (59 mg, 0.21 mmol) and mol. sieves
(4 ꢄ; 130 mg). After stirring for 7 h, the reaction was quenched by ice-cold H2O, and the mixture stirred
for 10 min. It was filtered out Celite pad and extracted with AcOEt. The org. layer were washed with
brine, dried (MgSO4), filtered, and concentrated. Purification of crude product by CC (SiO2; hexane/
AcOEt 15 :1) afforded syn-9 (17.5 mg, 0.0517 mmol, 98%). Colorless oil. [a]D ¼ þ13.2 (c ¼ 1.25, Et2O).
Rf (hexane/AcOEt 6 :1) 0.63. IR (film): 3400s (br.), 2950s, 1700s (C¼O), 1080s, 1000s. 1H-NMR
(300 MHz): 5.72 (s, HꢀC(8)); 5.31 (q, J ¼ 6.3, HꢀC(10)); 4.09 (d, J ¼ 8.1, HꢀC(6)); 2.78 (dq, J ¼ 6.9,
8.4, HꢀC(5)) 2.35 (t, J ¼ 6.9, CH2(3)); 1.72 (s, MeꢀC(7)); 1.67 (s, MeꢀC(9)); 1.66 (d, J ¼ 6.9, Me(11));
1.52 (sext., J ¼ 6.9, CH2(2)); 1.10 (d, J ¼ 6.6, MeꢀC(5)); 0.93 (t, J ¼ 8.1, (MeCH2)3Si); 0.87 (t, J ¼ 7.5,
Me(1)); 0.58 (q, J ¼ 7.8, (MeCH2)3Si). 13C-NMR (150 MHz): 213.4; 134.6; 132.7; 131.2; 124.3; 80.3; 51.2;
44.9; 22.6; 16.7; 13.7; 13.6; 13.4; 13.1; 6.84; 4.78. FAB-MS: 339 ([M þ H]þ), 239, 227, 209, 137, 115
([Et3Si]þ), 87. HR-FAB-MS: 339.2716 ([M þ H]þ, C20H39O2Siþ; calc. 339.2719).
(5R,6R,7E,9E)-Isomer (ent-syn-9). In the same manner as described for syn-13, ent-syn-13 (60.8 mg,
0.178 mmol) afforded ent-syn-9 (52.8 mg, 0.156 mmol, 88%). Colorless oil. [a]2D4 ¼ ꢀ12 (c ¼ 0.15, Et2O).
HR-FAB-MS: 361.2543 ([M þ Na]þ, C20H38NaO2Siþ; calc. 361.2538).
(5S,6S,7E,9E)-6-Hydroxy-5,7,9-trimethylundeca-7,9-dien-4-one ((ꢀ)-(5S,6S)-1). A soln. of syn-9
(15 mg, 0.0443 mmol) in THF (0.5 ml) was added dropwise to a soln. TBAF/HF (pH 7; prepared by
mixing 1m TBAF in THF and 47% aq. HF) at 08. After stirring for 30 min at 08, the mixture was poured
into brine and extracted with AcOEt. The extract was washed with brine, dried (MgSO4), and
concentrated in vacuo. The residue was submitted to CC (SiO2; hexane/AcOEt 15 :1) to give (5S,6S)-1
(7 mg, 0.0312 mmol, 70%). Colorless oil. [a]D24 ¼ ꢀ66 (c ¼ 0.045, hexane). Rf (hexane/AcOEt 4 :1) 0.30.
HPLC (column, Daicel Chiralcelꢀ OJ, 4.6 ꢁ 250 mm; temp., 258; eluent, hexane/i-PrOH 100 :1 at 0.5 ml/
min; detection at 234 nm): tR 19.6 (96% ee, 91% de). IR (film): 3420s (OH), 2950s, 1700s (C¼O),
1450m, 1020m. 1H-NMR (300 MHz, C6D6): 6.14 (s, HꢀC(8)); 5.42 (qt, J ¼ 6.9, 1.3, HꢀC(10)); 4.22
(pseudo-d, J ¼ 4.0, HꢀC(6)); 2.48 (qd, J ¼ 7.1, 4.9, HꢀC(5)); 2.27 (d, J ¼ 2.7, OH); 2.04 (td, J ¼ 6.8, 1.6,
CH2(3)); 1.68 (pseudo-s, Me); 1.65 (d, J ¼ 1.3, Me); 1.59 (d, J ¼ 6.9, Me(11)); 1.51 (sext., J ¼ 7.4, CH2(2));
1.04 (d, J ¼ 7.1, Me ꢀC(5)); 0.78 (t, J ¼ 7.5, Me(1)). 1H-NMR (300 MHz, CDCl3): 5.95 (s, HꢀC(8)); 5.37
(q, J ¼ 6.6, HꢀC(10)); 4.32 (br. s, HꢀC(6)); 2.76 (dq, J ¼ 7.2, 4.5, HꢀC(5)); 2.48 (t, J ¼ 7.2, CH2(3));
1.72 (s, MeꢀC(7), MeꢀC(9)); 1.68 (d, J ¼ 6.9, Me(11)); 1.60 (sext., J ¼ 7.2, CH2(2)); 1.08 (d, J ¼ 7.2,
MeꢀC(5)); 0.92 (d, J ¼ 7.2, Me(1)). 13C-NMR (75 MHz, C6D6): 213.8; 134.1; 133.7; 130.6; 124.4; 76.6;
49.1; 43.8; 17.1; 16.9; 14.8; 13.9; 13.7; 10.8. 13C-NMR (125 MHz): 215.4; 132.9; 132.8; 130.1; 124.4; 75.9;
48.5; 43.8; 16.9; 16.7; 15.0; 13.72; 13.66; 10.3. FAB-MS: 247 ([M þ Na]þ), 207, 125, 124, 71. HR-EI-MS:
.
224.1776 (Mþ , C14H24Oþ2 ; calc. 224.1776).
(5R,6R,7E,9E)-6-Hydroxy-5,7,9-trimethylundeca-7,9-dien-4-one ((þ)-(5R,6R)-1). In the same man-
ner as described for (5S,6S)-1, ent-syn-9 (3.2 mg, 0.0082 mmol) afforded (5R,6R)-1 (1.6 mg, 0.0071 mmol,
87%). Colorless oil. [a]2D4 ¼ þ66 (c ¼ 0.125, hexane). HPLC: tR 18.9 (98% ee, 90% de). HR-FAB-MS:
247.1677 ([M þ Na]þ, C14H24NaOþ2 ; calc. 247.1674).
Bioassay. Antifeedant activity of four diastereoisomers against a benthic fish (Notothenia coriiceps)
collected near Palmer Station, Anvers Island, on the western Antarctic Peninsula, was tested according
to the method described in [1b].
We thank Mr. Tsutomu Hasaba for technical assistance. This work was partially supported by grant-
in-aid from Japan Society for the Promotion of Science (Nos. 14760069 and 19580120), Intelligent Cosmos
Foundation, The Naito Foundation to H. K., and US National Science Foundation (OPP-0442857) to
B. J. B. The bioassays were conducted by Margaret Amsler, and supported by Prof. James B. McClintock
and Dr. Charles Amsler (University of Alabama at Birmingham, USA) under a grant from the US
National Science Foundation (OPP-0442769).

1944
Helvetica Chimica Acta – Vol. 93 (2010)
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Received July 7, 2010