Stereoselective total synthesis of xestodecalactone C

Article abstract of DOI:10.1002/hlca.200900068

A simple and highly efficient stereoselective total synthesis of xestodecalactone C (IIb), a polyketide natural product, was achieved (Scheme 2). The synthesis involved Keck's asymmetric allylation, a iodine-induced electrophilic cyclization, and an intra

Full text of DOI:10.1002/hlca.200900068

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Helvetica Chimica Acta – Vol. 92 (2009)
Stereoselective Total Synthesis of Xestodecalactone C
by Karuturi Rajesh, Vangaru Suresh, Jondoss Jon Paul Selvam, Chitturi Bhujanga Rao, and
Yenamandra Venkateswarlu*
Natural Products Laboratory, Organic Chemistry Division – I, Indian Institute of Chemical Technology,
Hyderabad 500007, India (phone: þ 91-40-27193167; fax: þ 91-40-27160512; e-mail: luchem@iict.res.in)
A simple and highly efficient stereoselective total synthesis of xestodecalactone C (IIb), a polyketide
natural product, was achieved (Scheme 2). The synthesis involved Keckꢀs asymmetric allylation, a iodine-
induced electrophilic cyclization, and an intramolecular Friedel – Crafts acylation as key steps.
Introduction. – Marine fungi are attracting increasing attention as a potential
source of new pharmaceuticals and pharmaceutical leads [1]. In 2002, 10-membered
macrolides fused to the 1,3-dihydroxybenzene ring such as xestodecalactones A (I), B
(IIa), and C (IIb) were isolated from the fungus Penicillium cf. mantanense obtained
from the marine sponge Xestospongia exigua [2]. A number of structurally related
molecules such as sporostatin1) (III) [3] and the curvularins1) IV, Va, and Vb [4] were
isolated from terrestrial fungi Sporormiella sp. and Penicillium sp., respectively.
Xestodecalactones A – C have been shown to exhibit antibacterial and antifungal
activities [5]. They are also found to be specific inhibitors of the epidermal growth
factor (EGF) receptor, tyrosine kinase in vitro. The potential biological importance as
well as the unique structural feature of these molecules sparked interest in the
syntheses of these molecules [6]. Pan and co-workers determined the absolute
configuration of xestodecalactones B and C by their stereoselective synthesis [7].
Recently, Yadav and co-workers reported the stereoselective total synthesis of
xestodecalactone C utilizing a Prins cyclization for the preparation of the aliphatic
segment and a Friedel – Crafts acylation for the construction of the macrolide [8]. In
continuation of our interest on the synthesis of biologically active natural products [9],
we report herein an efficient and practical total synthesis of xestodecalactone C.
1
)
Arbitrary atom numbering; for the systematic name of IIb, see Exper. Part.
ꢁ 2009 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Our planned approach to xestodecalactone C (IIb) involved an intramolecular
Friedel – Crafts acylation for the macrolide ring formation as reported earlier [7][8], an
asymmetric allylation, and a diastereoselective iodolactonization as the chirality-
inducing steps starting from propane-1,3-diol (Scheme 1).
Scheme 1. Retrosynthetic Approach to Xestodecalactone C (IIb)
Results and Discussion. – The synthesis of xestodecalactone C (IIb) started with
commercially available propane-1,3-diol (Scheme 2), which was protected with p-
methoxybenzyl (PMB) bromide to yield the corresponding propan-1-ol 1. The primary
alcohol in 1 was oxidized with 2-iodoxybenzoic acid (¼2-iodylbenzoic acid ¼ IBX; 2-
(O2I)-C6H4ꢀCOOH) in DMSO to afford the corresponding aldehyde, which was
subjected to the catalytic asymmetric allylation with an allylstannane developed by
Keck and co-workers [10] to furnish the homoallyl alcohol 2 in 80% yield with excellent
enantioselectivity (95% ee by HPLC). The homoallyl alcohol 2 was treated with
di(tert-butyl) dicarbonate ((Boc)2O) in the presence of DMAP in MeCN [11] to afford
the homoallyl tert-butyl carbonate 3. The latter was subjected to the diastereoselective
iodolactonization [12] with I2 in dry MeCN at ꢀ 208 to furnish the cyclic iodocarbonate
1
4 in 85% yield as a single diastereoisomer (as determined by H-NMR analysis).
Iodocarbonate 4, upon exposure to a basic MeOH solution [12], gave the desired ꢃsynꢀ-
epoxy alcohol 5 in 90% yield. The epoxy alcohol 5 was protected as benzyl ether 6 by
treatment of 5 with benzyl bromide/NaH. Then, the terminal epoxide 6 was subjected
to regioselective reduction with LiAlH4 [13] in THF to afford the secondary alcohol 7
which was esterified with 3,5-(dimethoxyphenyl)acetic acid in the presence of DCC and
DMAP [14] to give ester 8. The latter, on treatment with DDQ in CH2Cl2/H2O,
afforded the primary alcohol 9 which was oxidized with Jones reagent (5 equiv.) in
acetone at 08 for 15 min to afford the acid 10 in 86% yield [15]. The desired macrolide
11 was obtained in 40% yield by an intramolecular Friedel – Crafts acylation reaction of
the carboxylic acid 10 in the presence of CF3COOH/(CF3CO)2O [8][16]. The benzyl
protecting group of 11 was removed by using 5% Pd/C under H2 in AcOEt to afford 12.
Finally, the MeO groups were removed by reaction with freshly prepared AlI3 [17] to
furnish the natural product IIb. The spectroscopic and analytical data of IIb are in good
agreement with the data reported for the natural product.
In conclusion, an efficient and straightforward total synthesis of xestodecalactone C
(IIb) was achieved. The initial Keck asymmetric allylation of an aldehyde for the
introduction of chirality and the subsequent diastereoselective I2-induced electrophilic
cyclization constitute the key reactions for the construction of the ꢃsynꢀ-1,3-diol moiety.
The synthetic strategy described here has significant potential for the synthesis of a
variety of other biologically important substituted 1,3-diol-containing natural products.

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Scheme 2
a) 2-Iodoxybenzoic acid, DMSO, CH2Cl2, 3 h; 90%. b) (þ)-(R)-BINOL ((þ)-(1R)-[1,1’-binaphthalene]-
2,2’-diol), 4 ꢄ molecular sieves, Ti(iPrO)4, allyltributylstannane, CH2Cl2, ꢀ 788 to ꢀ 208. c) (Boc)2O,
DMAP (N,N-dimethylpyridin-4-amine), MeCN, r.t., 5 h; 95%. d) I2, MeCN, ꢀ 208, 12 h; 85%. e)
K2CO3, MeOH, 08 to r.t., 30 min; 90%. f) BnBr, NaH, THF, r.t., 6 h; 85%. g) LiAlH4, THF, 08 to r.t., 2 h;
90%. h) DCC (dicyclohexylcarbodiimide), DMAP, r.t., Et2O; 95%. i) DDQ (4,5-dichloro-3,6-
dioxocyclohexa-1,4-diene-1,2-dicarbonitrile), CH2Cl2/H2O 19 :1, r.t., 1 h; 80%. j) Jones reagent, 08,
15 min; 86%. k) CF3COOH/(CF3CO)2O, reflux; 40%. l) H2, Pd/C, AcOEt, r.t.; 90%. m) AlI3, (Bu4N)I,
benzene, r.t.; 96%.
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 over
anh. Na2SO4 and concentrated in vacuo below 408. Column chromatography (CC): silica gel (Acmeꢀs 60 –
120 mesh). HPLC: Eurocel 01 (250 ꢁ 4.6 mm, 5 mm); mobile phase hexane/i-PrOH 90 :10, flow rate 1 ml/

Helvetica Chimica Acta – Vol. 92 (2009)
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min; detection by PDA (photo diode array). Optical rotations: Horiba high-sensitive polarimeter SEPA-
300; at 258. IR Spectra: Perkin-Elmer-IR-683 spectrophotometer with NaCl optics. 1H- (200 and
300 MHz) and 13C-NMR (50 and 75 MHz) Spectra: Varian-Gemini-FT-200 and Bruker-Avance-300
instruments; Me4Si as internal standard in CDCl3; J values in Hz. MS: Agilent Technologies 1100 series
(Agilent Chemistation software); in m/z (rel. %).
1-[(4-Methoxybenzyl)oxy]hex-5-en-3-ol (2). To a stirred soln. of 2-iodoxybenzoic acid (3.2 g,
11.47 mmol) in dry DMSO (5 ml), a soln. of 3-[(4-methoxybenzyl)oxy]propan-1-ol (1; 1.5 g, 7.6 mmol) in
CH2Cl2 (50 ml) was added at r.t. and stirred for 5 h at r.t. After completion of the reaction, the mixture
was filtered, diluted with H2O (50 ml) and extracted with CH2Cl2 (2 ꢁ 50 ml). The combined org. layer
was washed with brine (20 ml), dried (Na2SO4), and evaporated to give the crude aldehyde which was
purified by CC (hexane/AcOEt 1:9): aldehyde (1.36 g, 92%) as a colorless liquid. Separately, a mixture
of (þ)-(R)-BINOL (0.2 g, 0.7 mmol) and Ti(iPrO)4 (0.2 g, 0.7 mmol) in CH2Cl2 (30 ml) in the presence of
4 ꢄ molecular sieves (2 g) was stirred under reflux. After 1 h, the mixture was cooled to r.t., the
previously prepared aldehyde (1.36 g, 7 mmol) was added, and the resulting mixture was stirred for
10 min. Then, the mixture was cooled to ꢀ 788, and allyltributylstannane (2.7 g, 8.4 mmol) was added and
the stirring continued at ꢀ 208 for 36 h. After completion of the reaction (TLC), it was quenched with
sat. NaHCO3 soln. (5 ml), stirred for an additional 30 min, and then extracted with CH2Cl2 (40 ml). The
org. phase was washed with H2O (15 ml), dried, and concentrated and the residue purified by CC
(AcOEt/hexane 2 :8): 2 (1.32 g, 80%). Clear liquid. [a]2D5 ¼ þ3.2 (c ¼ 1, CHCl3); 95% ee by HPLC. IR
(neat): 3445, 3072, 2930, 2861, 1612, 1513,1461, 1362, 1300, 1247, 1175, 1089, 1033. 1H-NMR (300 MHz,
CDCl3): 7.22 (d, J ¼ 8.1, 2 H); 6.84 (d, J ¼ 8.8, 2 H); 5.86 – 5.76 (m, 1 H); 5.1 – 5.06 (m, 2 H); 4.4 (s, 2 H);
3.9 – 3.85 (m, 1 H), 3.8 (s, 3 H); 3.68 – 3.63 (m, 1 H); 2.2 (t, J ¼ 7.3, 2 H); 1.74 – 1.68 (m, 2 H). 13C-NMR
(75 MHz, CDCl3): 159.1; 134.8; 130.1; 129.2; 117.4; 113.7; 72.8; 70.28; 68.48; 55.19; 41.8; 35.70. HR-ESI-
MS: 259.1318 ([M þ Na]þ, C14H20NaO3þ ; calc. 259.1310).
(3R)-tert-Butyl 1-[(4-Methoxybenzyl)oxy]hex-5-en-3-yl Carbonate (¼1,1-Dimethylethyl (1R)-1-{3-
[(4-Methoxyphenyl)methoxy]propyl}but-3-en-1-yl Carbonate; 3). To a soln. of 2 (1.32 g, 5.5 mmol) in
MeCN (40 ml) were added (Boc)2O (1.22 g, 5.5 mmol) and DMAP (0.26 g, 2.1 mmol) and stirred for 5 h.
After completion of the reaction, the solvent was evaporated. The residue was dissolved in CH2Cl2
(100 ml), the org. phase washed with 5% HCl soln. (3 ꢁ 50 ml), dried, and concentrated, and the crude
product purified by CC (silica gel, petroleum ether/AcOEt 9 :1): 3 (1.78 g, 95%). Colorless oil. [a]D25
¼
1
þ1.9 (c ¼ 1, CHCl3). IR (neat.): 2978, 2929, 1756, 1613, 1368, 1275, 1251, 1058. H-NMR (300 MHz,
CDCl3): 7.25 (d, J ¼ 8.07, 2 H); 6.84 (d, J ¼ 8.79, 2 H); 5.9 – 5.76 (m, 1 H); 5.1 – 5.06 (m, 2 H); 4.95 – 4.8
(m, 1 H), 4.45 (s, 2 H); 3.8 (s, 3 H); 3.58 – 3.43 (m, 2 H); 2.4 (t, J ¼ 7.32, 2 H); 1.8 – 1.69 (m, 2 H); 1.5 (s,
9 H). LC/MS: 359 ([M þ Na]þ).
(4S,6S)-4-(Iodomethyl)-6-{2-[(4-methoxybenzyl)oxy]ethyl}-1,3-dioxan-2-one (4). To a stirred soln.
of 3 (1.5 g, 4.46 mmol) in dry MeCN (100 ml) was added I2 (3.39 g, 13.3 mmol) at ꢀ 408 for 10 h. After
completion of the reaction (TLC), aq. Na2S2O3 soln. (50 ml), followed by aq. NaHCO3 soln. (50 ml) was
added. The mixture was then extracted with AcOEt (3 ꢁ 50 ml), the extract washed with H2O (15 ml),
dried, and concentrated, and the residue purified by CC (AcOEt/hexane 3 :7): pure 4 (1.45 g, 80%).
Colorless oil. [a]D25 ¼ ꢀ4.6 (c ¼ 1.2, CHCl3). IR (neat): 2924, 2856, 1746, 1611, 1512, 1389, 1245, 1183,
1096, 1030, 820, 761. 1H-NMR (300 MHz, CDCl3): 7.25 (d, J ¼ 8.5, 2 H); 6.8 (d, J ¼ 8.7, 2 H); 4.71 – 4.61
(m, 1 H); 4.45 – 4.36 (m, 3 H); 3.8 (s, 3 H); 3.7 – 3.54 (m, 2 H); 3.4 – 3.35 (m, 1 H); 3.28 – 3.22 (m, 1 H);
2.4 – 2.33 (m, 1 H); 2.0 – 1.91 (m, 2 H); 1.7 – 1.64 (m, 1 H). 13C-NMR (75 MHz, CDCl3): 159.3; 148.3;
129.9; 129.4; 113.8; 77.2; 75.8; 72.9; 64.5; 55.2; 35.3; 33.2; 5.4. HR-ESI-MS: 429.0155 ([M þ Na]þ,
C15H19INaOþ5 ; calc. 429.0175).
(2S)-4-[(4-Methoxybenzyl)oxy]-1-[(2S)-oxiran-2-yl]butan-2-ol (5). To a stirred soln. of 4 (1.45 g,
3.5 mmol) in MeOH (20 ml) was added K2CO3 (2.46 g, 17.8 mmol) at 08. The mixture was then warmed
and stirred at 258. After completion of the reaction (TLC), aq. NaHCO3 soln. (50 ml) was added, and the
mixture was extracted with AcOEt (3 ꢁ 50 ml). The combined org. phase was dried and concentrated
and the residue purified by CC (AcOEt/hexane 4 :6): 5 (0.783 g, 87%). Colorless oil. [a]2D5 ¼ þ4.8 (c ¼
1
1.3, CHCl3). IR (neat): 3430, 2928, 2866, 1611, 1512, 1389, 1345, 1189, 1096, 1030, 825, 781. H-NMR
(300 MHz, CDCl3): 7.24 (d, J ¼ 8.7, 2 H); 6.87 (d, J ¼ 8.5, 2 H); 4.45 (s, 2 H); 4.1 – 4.0 (m, 1 H); 3.79 (s,
3 H); 3.73 – 3.59 (m, 2 H); 3.12 – 3.06 (m, 1 H); 2.78 – 2.75 (m, 1 H); 2.51 – 2.48 (m, 1 H); 1.86 – 1.61 (m,

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Helvetica Chimica Acta – Vol. 92 (2009)
4 H). 13C-NMR (75 MHz, CDCl3): 159.2; 129.9; 129.2; 113.8; 72.9; 69.4; 68.5; 55.2; 49.9; 46.6; 39.8; 36.3.
HR-ESI-MS: 275.1265 ([M þ Na]þ, C14H20NaOþ4 ; calc. 275.1259).
(2S)-2-{(2S)-2-(Benzyloxy)-4-[(4-methoxybenzyl)oxy]butyl}oxirane (6). A soln. of 5 (0.7 g,
2.77 mmol) in anh. THF was slowly added to a 60% NaH suspension in oil (0.166 g, 6.92 mmol)
followed by the addition of benzyl bromide (0.36 ml, 3 mmol). The mixture was stirred at r.t. for 4 h,
quenched with cold H2O, and extracted with AcOEt (3 ꢁ 50 ml). The org. phase was dried and
concentrated and the residue purified by CC (AcOEt/hexane 2 :8): 6 (0.9 g, 95%). Colorless oil. [a]D25
¼
þ5.2 (c ¼ 1.1, CHCl3). IR (neat): 2923, 2854, 1723, 1610, 1510, 1456, 1356, 1298, 1245, 1173, 1090, 840,
760, 697. 1H-NMR (300 MHz, CDCl3): 7.35 (m, 7 H); 6.86 (d, J ¼ 8.7, 2 H); 4.56 – 4.36 (m, 4 H); 3.81 – 3.79
(m, 1 H); 3.78 (s, 3 H); 3.63 – 3.5 (m, 2 H); 3.08 – 3.01 (m, 1 H); 2.74 – 2.71 (m, 1 H); 2.46 – 2.43 (m, 1 H);
1.95 – 1.76 (m, 4 H). 13C-NMR (75 MHz, CDCl3): 159.1; 138.5; 130.4; 129.3; 128.3; 127.7; 127.5; 113.7;
74.1; 72.6; 71.2; 66.2; 55.2; 49.4; 46.7; 37.0; 34.6. HR-ESI-MS: 365.1710 ([M þ Na]þ, C21H26NaO4þ ; calc.
365.1729).
(2R,4S)-4-(Benzyloxy)-6-[(4-methoxybenzyl)oxy]hexan-2-ol (7). A soln. of 6 (0.9 g, 2.63 mmol) in
THF (20 ml) was added slowly to a stirred slurry of LiAlH4 (0.2 g, 5.2 mmol) in THF. After being stirred
for 6 h at 508, the reaction was carefully quenched with H2O. The mixture was extracted with AcOEt (3 ꢁ
50 ml), the org. phase dried (anh. Na2SO4) and concentrated, and the residue purified by CC (AcOEt/
hexane 3 :7): 7 (0.79 g, 88%). Colorless oil. [a]2D5 ¼ þ6.2 (c ¼ 1.2, CHCl3). IR (neat): 3430, 2925, 2855,
1735, 1611, 1512, 1456, 1246, 1174, 1090, 1033, 938, 819, 770. 1H-NMR (300 MHz, CDCl3): 7.34 – 7.21 (m,
7 H); 6.86 (d, J ¼ 8.7, 2 H); 4.65 – 4.38 (m, 4 H); 3.95 – 3.79 (m, 1 H); 3.78 (s, 3 H); 3.58 – 3.45 (m, 2 H);
2.68 (br. s, 1 H); 2.0 – 1.52 (m, 4 H); 1.12 (d, J ¼ 6.2, 3 H). 13C-NMR (75 MHz, CDCl3): 159.1; 137.8;
130.2; 129.3; 128.5; 128.4; 127.8; 127.7; 113.7; 77.1; 72.6; 70.9; 67.3; 66.0; 55.1; 43.0; 33.9; 23.5. HR-ESI-
MS: 367.1866 ([M þ Na]þ, C21H28NaO4þ ; calc. 367.1885).
(2R,4S)-4-(Benzyloxy)-6-[(4-methoxybenzyl)oxy]hexan-2-yl 2-(3,5-Dimethoxyphenyl)acetate
(¼(1R,3S)-5-[(4-Methoxyphenyl)methoxy]-1-methyl-3-(phenylmethoxy)pentyl 3,5-Dimethoxybenzene-
acetate; 8). To a stirred soln. of 7 (0.2 g, 0.58 mmol) in CH2Cl2 (10 ml) was added DCC (0.179 g,
0.872 mmol) followed by a catalytic amount of DMAP at 08. After 5 min, 2-(3,5-dimethoxyphenyl)acetic
acid (0.136 g, 0.692 mmol) was added, and the mixture was stirred for 17 h at r.t. After completion of the
reaction (TLC), H2O (10 ml) was added, and the mixture was extracted with CH2Cl2 (20 ml). The org.
layer was washed successively with 10% aq. HCl soln., sat. NaHCO3 soln., and brine, dried, and
concentrated and the residue purified by CC (AcOEt/hexane 1:10): 8 (0.29 g, 95%). [a]2D5 ¼ þ9.7 (c ¼ 1,
CHCl3). IR (neat): 2923, 2853, 1731, 1601, 1512, 1461, 1294, 1250, 1204, 1155, 1101, 1066, 832. 1H-NMR
(300 MHz, CDCl3): 7.34 – 7.21 (m, 7 H); 6.85 (d, J ¼ 8.7, 2 H); 6.42 – 6.29 (m, 3 H); 5.1 – 5.02 (m, 1 H);
4.42 – 4.35 (m, 4 H); 3.78 – 3.72 (m, 10 H); 3.57 – 3.46 (m, 4 H); 2.0 – 1.59 (m, 4 H); 1.18 (d, J ¼ 6.2, 3 H).
13C-NMR (75 MHz, CDCl3): 170.7; 160.7; 159.1; 138.5; 136.2; 130.5; 129.2; 128.3; 127.7; 127.5; 113.7;
107.2; 99.0; 73.3; 72.5; 70.8; 69.0; 66.3; 55.2; 42.0; 40.3; 34.1; 20.2. HR-ESI-MS: 545.2513 ([M þ Na]þ,
C31H38NaOþ7 ; calc. 545.2515).
(2R,4S)-4-(Benzyloxy)-6-hydroxyhexan-2-yl 2-(3,5-Dimethoxyphenyl)acetate (¼(1R,3S)-5-Hy-
droxy-1-methyl-3-(phenylmethoxy)pentyl 3,5-Dimethoxybenzeneacetate; 9). To a soln. of 8 (290 mg,
0.55 mmol) in CH2Cl2/H2O 19 :1 (20 ml) at 08 was added DDQ (252 mg, 1.1 mmol), and the mixture was
stirred at r.t. for 2 h. After completion of the reaction (TLC), it was quenched with sat. aq. NaHCO3 soln.
and the mixture, extracted with CH2Cl2 (3 ꢁ 20 ml). The org. phase was dried (anh. Na2SO4), the solvent
removed under reduced pressure, and the residue purified by CC (AcOEt/hexane 2 :8): 9 (208 mg, 90%).
Colorless syrup. [a]2D5 ¼ ꢀ5.2 (c ¼ 1, CHCl3). IR (neat): 3445, 2927, 2851, 1728, 1599, 1461, 1430, 1294,
1252, 1204, 1154, 1062, 837, 746. 1H-NMR (300 MHz, CDCl3): 7.36 – 7.23 (m, 5 H); 6.44 – 6.32 (m, 3 H);
5.03 – 4.95 (m, 1 H); 4.49 – 4.29 (m, 2 H); 3.79 – 3.64 (m, 8 H); 3.53 – 3.45 (m, 3 H); 2.08 – 1.98 (m, 2 H);
1.8 – 1.74 (m, 1 H); 1.7 – 1.6 (m, 1 H); 1.24 (d, J ¼ 6.0, 3 H). 13C-NMR (75, CDCl3): 170.8; 160.8; 138.03;
136.2; 128.4; 128.4; 127.8; 107.3; 98.9; 75.4; 70.9; 68.6; 60.4; 55.3; 42.1; 39.9; 35.9; 20.5. ESI-MS: 425
([M þ Na]þ).
(3R,5R)-3-(Benzyloxy)-5-{[2-(3,5-dimethoxyphenyl)acetyl]oxy}hexanoic Acid (10). To a soln. of 9
(208 mg, 0.517 mmol) in acetone (50 ml) was added 1m Jones reagent (1.1 ml) at 08, and the mixture was
stirred at 08 for 15 min. After completion of the reaction iPrOH was added, and the resulting mixture was
filtered through Celite, the filtrate concentrated, the residue dissolved in AcOEt (50 ml), and the soln.

Helvetica Chimica Acta – Vol. 92 (2009)
1871
washed with brine (3 ꢁ 15 ml), dried, and concentrated. The residue was purified by CC (silica gel,
hexane/AcOEt 60 :40): 10 (185 mg, 86%). Colorless oil. [a]2D5 ¼ ꢀ3.8 (c ¼ 1, CHCl3). IR (neat): 3350,
2950, 1726, 1600, 1449, 1429, 1259, 1154, 1062. 1H-NMR (300 MHz, CDCl3): 7.36 – 7.23 (m, 5 H); 6.44 –
6.32 (m, 3 H); 5.03 – 4.95 (m, 1 H); 4.49 – 4.29 (m, 2 H); 3.79 – 3.64 (m, 6 H); 3.53 – 3.45 (m, 3 H); 2.48 –
2.23 (m, 2 H); 1.7 – 1.6 (m, 2 H); 1.24 (d, J ¼ 6.24, 3 H). 13C-NMR (75 MHz, CDCl3): 178.3; 172.3, 162.8;
138.23; 136.4; 128.5; 128.4; 127.9; 106.3; 99.3; 72.4; 71.3; 68.8; 60.7; 55.3, 46.3; 42.1; 40.2; 35.9; 20.5. LC/
MS: 439 ([M þ Na]þ).
(4R,6R)-6-(Benzyloxy)-4,5,6,7-tetrahydro-9,11-dimethoxy-4-methyl-2H-3-benzoxecin-2,8(1H)-di-
one (11). The acid 10 (185 mg, 0.44 mmol) was dissolved in CF3COOH/(CF3CO)2O 4 :1 (5 ml), and the
soln. was stirred for 8 h at r.t. After completion of the reaction (TLC), the mixture was poured into an
excess of NaHCO3 soln., and extracted with Et2O (3 ꢁ 25 ml). The combined extract was washed with
H2O, the org. phase dried and concentrated, and the residue purified by CC (AcOEt/hexane 2 :8): 11
(70 mg, 40%). Reddish oil. [a]2D5 ¼ ꢀ6.2 (c ¼ 1.1, CHCl3). IR (neat): 2925, 1730, 1634, 1610, 1459, 1336,
1239, 1157, 1089. 1H-NMR (300 MHz, CDCl3): 7.36 – 7.17 (m, 5 H); 6.37 (d, J ¼ 1.5, 1 H); 6.21 (d, J ¼ 1.5,
1 H); 4.91 – 4.81 (m, 1 H); 4.57 (m, 2 H); 4.27 – 4.17 (m, 1 H); 4.01 – 3.89 (m, 1 H); 3.84 (s, 3 H); 3.80 (s,
3 H); 3.38 – 3.28 (m, 1 H); 3.15 – 3.06 (m, 2 H); 2.10 – 2.01 (m, 1 H); 1.80 – 1.74 (m, 1 H); 1.20 (d, J ¼ 6.5,
3 H). 13C-NMR (75 MHz, CDCl3): 204.59; 168.75; 161.33; 159.02; 138.24; 134.4; 128.36; 127.65; 124.19;
107.75; 96.94; 71.70; 70.72; 55.65; 55.36; 52.35; 43.66; 40.31; 29.62; 20.84. HR-ESI-MS: 421.1620 ([M þ
Na]þ, C23H26NaOþ6 ; calc. 421.1627).
(4R,6R)-4,5,6,7-Tetrahydro-6-hydroxy-9,11-dimethoxy-4-methyl-2H-3-benzoxecin-2,8(1H)-dione
(12). To a suspension of 5% (Pd/C 15 mg) in AcOEt (5 ml) was added a soln. of 11 (45 mg, 0.11 mmol) in
AcOEt (3 ml). The mixture was stirred at r.t. for 12 h under 4 atm of H2 pressure. After completion of the
reaction, the mixture was filtered and concentrated. The residue was purified by CC (silica gel, petroleum
ether/AcOEt 8 :2): 12 (31 mg, 91%). Colorless liquid. [a]2D0 ¼ þ13.6 (c ¼ 1, CHCl3). IR (neat): 3345,
1
2945, 1740, 1620, 1456, 1378, 1125. H-NMR (300 MHz, CDCl3): 6.39 (s, 1 H); 6.27 (s, 1 H); 5.38 – 5.09
(m, 1 H), 4.29 – 4.11 (m, 1 H); 3.82 (s, 3 H); 3.81 (s, 3 H); 3.51 – 3.4 (d, J ¼ 13.5, 1 H), 3.09 (s, 2 H), 2.39 –
2.21 (m, 1 H), 2.19 – 1.91 (m, 1 H), 1.82 – 1.4 (m, 1 H); 1.19 (d, J ¼ 6.4, 3 H). LC/MS: 331 ([M þ Na]þ).
Xestodecalactone C (¼(4R,6R)-4,5,6,7-Tetrahydro-6,9,11-trihydroxy-4-methyl-2H-3-benzoxecin-
2,8(1H)-dione; IIb). A mixture of I2 crystals (0.29 g, 1.16 mmol) and Al powder (0.042 g, 1.56 mmol)
was taken up in dry benzene (10 ml), refluxed for 1 h, and then cooled to r.t. To this soln., a mixture of
(Bu4N)I (0.0018 g, 0.0050 mmol) and 12 (0.012 g, 0.038 mmol) in dry benzene (5 ml) was added. The
resulting mixture was stirred for 45 min at 108. After completion of the reaction (TLC), it was quenched
with AcOEt (3 ꢁ 10 ml). The org. phase was washed with brine, dried, and concentrated and the residue
purified by CC (AcOEt/hexane 1:1): IIb (0.0010 mg, 96%). White solid. M.p. 166 – 1688. [a]2D0 ¼ þ29
(c ¼ 0.7, MeOH). IR (KBr): 3345, 2923, 1739, 1630, 1601, 1461, 1370, 1165. 1H-NMR (400 MHz,
(D6)DMSO): 9.92 (s, 1 H); 9.71 (s, 1 H); 6.27 (d, J ¼ 1.7, 1 H); 6.10 (s, 1 H); 4.75 (d, J ¼ 4.0, 1 H); 4.72
(dd, J ¼ 11.2, 5.6, 1 H); 3.96 (br. s, 1 H); 3.80 (d, J ¼ 19.0, 1 H); 3.48 (d, J ¼ 19.0, 1 H); 3.08 (dd, J ¼ 14.8,
10.4, 1 H); 2.81 (d, J ¼ 14.5, 1 H); 1.83 (d, J ¼ 13.0, 1 H); 1.63 (dd, J ¼ 14.8, 11.2, 1 H); 1.08 (d, J ¼ 6.5,
3 H). 13C-NMR (75 NHz, (D6)DMSO): 204.51; 167.75; 159.15; 157.02; 134.44; 121.80; 110.0; 101.25;
70.64; 67.78; 55.17; 45.99; 20.73. HR-MS: 303.0843 ([M þ Na]þ, C14H16NaO6þ ; calc. 303.0839).
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Received February 26, 2009