Facile total synthesis of benzo[b]furan natural product XH-14

Article abstract of DOI:10.1080/00397910802399924

An efficient and practical total synthesis of benzo[b]furan natural product XH-14 is demonstrated in nine steps from vanillin. Introduction of iodide substituents in the reaction including optimization of the reaction sequences is essential for the successful synthesis of XH-14. Sonogashira coupling with iodobenzene, iodine-induced cyclization, Wittig reaction, and formylation are critical in the high-yield total synthesis of XH-14. Copyright Taylor & Francis Group, LLC.

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Facile Total Synthesis of
Benzo[b]furan Natural Product
XH-14
Hyun Bae Bang a , Su Young Han a , Da Hye Choi a
Deok Mo Yang a , Jung Woon Hwang a , Hyun Suck
Lee a & Jong-Gab Jun a
,
a Department of Chemistry and Institute of Applied
Chemistry, Hallym University, Chuncheon, Korea
Published online: 08 Jan 2009.
To cite this article: Hyun Bae Bang , Su Young Han , Da Hye Choi , Deok Mo Yang ,
Jung Woon Hwang , Hyun Suck Lee & Jong-Gab Jun (2009) Facile Total Synthesis of
Benzo[b]furan Natural Product XH-14, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:3, 506-515, DOI:
10.1080/00397910802399924
To link to this article: http://dx.doi.org/10.1080/00397910802399924
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Synthetic Communications1, 39: 506–515, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802399924
Facile Total Synthesis of Benzo[b]furan Natural
Product XH-14
Hyun Bae Bang, Su Young Han, Da Hye Choi, Deok Mo Yang,
Jung Woon Hwang, Hyun Suck Lee, and Jong-Gab Jun
Department of Chemistry and Institute of Applied Chemistry,
Hallym University, Chuncheon, Korea
Abstract: An efficient and practical total synthesis of benzo[b]furan natural
product XH-14 is demonstrated in nine steps from vanillin. Introduction of iodide
substituents in the reaction including optimization of the reaction sequences is
essential for the successful synthesis of XH-14. Sonogashira coupling with iodo-
benzene, iodine-induced cyclization, Wittig reaction, and formylation are critical
in the high-yield total synthesis of XH-14.
Keywords: Benzofuran, danshen, lignan, Sonogashira coupling, XH-14
2-(4-Hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxybenzo-
furan-3-carbaldehyde (XH-14, 1, Fig. 1) is a benzo[b]furan lignan natural
product and was isolated from Salvia miltiorrhiza Bunge (Chinese name
‘‘Danshen’’), which has been widely used in China for the treatment of
cardiovascular diseases such as acute myocardial infarction and angina
pectoris.[1] It was the first reported nonnucleoside-type potent adenosine
A1 agonist and showed a high potency (IC50 ¼ 17 nM) in the bovine ade-
nosine A1 radioligand binding assay.[2] However, the limited supply
(approximately 0.1 ppm) of XH-14 from Danshen has prevented the
diverse characterization of its biological activities.[3] Since the initial total
synthesis of 1 by Yang et al. in 1991,[3] several syntheses have been
reported by Yang et al.,[4] Luetjens[4] and Scammells,[5] and, Kao and
Chern[6] using Sonogashira coupling reactions.[7] However, the synthetic
Received April 18 2008.
Address correspondence to Jong-Gab Jun, Department of Chemistry and Insti-
tute of Applied Chemistry, Hallym University, Chuncheon, Korea. E-mail:
jgjun@hallym.ac.kr
506

Total Synthesis of XH-14
507
Figure 1. Structure of XH-14.
yields and steps are not optimized. We report herein the convenient and
practical total synthesis of XH-14 (1) in nine steps from vanillin by using
Sonogashira coupling reactions with iodine-induced cyclization.
In the present work, a key feature is the introduction of iodine sub-
stituents in the reaction including optimization of the synthetic sequences
as part of a convenient route for the synthesis of XH-14.
To find the optimized reaction sequences, we investigated regioselec-
tive halogenations, Sonogashira couplings, and halogen-induced cycliza-
tions in different substituents. The halogenation was quite sensitive,
depending on substituents as shown in Scheme 1.[8] Vanillin 2 reacted
with Br2 in AcOH at rt, to give o-bromophenol 3a in 87% yield and with
I2 and Ag2SO4 in EtOH at rt, yielding o-iodophenol 3b in 80% yield.
However, substituents 4 and 5 showed no reactions both in bromination
and iodination. Bromination of 6 gave quantitative yield of m-benzyloxy-
bromobenzene 7a without any o-bromo-product, but iodination gave no
result. Methoxyvanillin 8 gave m-bromo 9a (65%) and m-iodo 9b
(50%)[8b] products regioselectively compare to o-haloproduct 3. To
obtain the regioselective o-haloproduct for Sonogashira coupling to give
benzofuran structure, the hydroxyl functional group should be main-
tained before halogenation reaction.
Sonogashira coupling reactions were also sensitive to the haloaryl substi-
tuents as shown in Scheme 2. Bromomethoxyvanillin 10a was not reacted
with acetylene 11, which is easily prepared from benzylated vanillin by Colvin
rearrangement,[9] by using PdCl2(PPh3)2=CuI=triethylamine (TEA)=
N,N-dimethylformamide (DMF) to give coupled product, but iodo-deriva-
tive 10b gave the expected coupled diarylyne 12 in 89% yield. Also, iodophe-
nol 13b showed much higher yield in Sonogashira coupling reaction than
bromophenol 13ato give benzofuran 14. Benzofuran structure 14 wasformed
during the Sonogashira coupling reaction after formation of the coupled dia-
rylyne, which reacted with an intrahydroxyl group to form benzofuran ring
in oneflask. The regioselective formylation of benzofuran sometimes showed
difficulties using Gattermann–Adams or Vilsmeier–Haack reactions.[4]

508
H. B. Bang et al.
Scheme 1. Reagents and conditions: (a) Br2, AcOH rt, (b) I2, Ag2SO4, EtOH, rt.
To avoid this formylation problem, we should protect the further reaction of
diarylyne to benzofuran ring cyclization during Sonogashira coupling reac-
tion. Protection of the free hydroxyl group of 3 by methylation with tetrabu-
tylammonium iodide (TBAI)=NaOH=MeI, producing 10 in 97% yield, will
prohibit insitu benzofuran ring cyclization during coupling reaction. The
halogen-induced cyclization of coupled diarylyne 12 yielded 3-halobenzo-
furan 15 as shown in Scheme 3.[6] Iodine (2 equiv)–induced benzofuran ring
formation showed much higher yield (15b, 95%) than bromobenzofuran
15a (30%) through a cyclic halonium intermediate.
The Wittig reaction of iodobenzofuranaldehyde (15b) in methylene
chloride at reflux with (carbethoxymethylene)triphenylphosphorane pro-
duced 93% yield of only (E)-16, which was then reduced to 17 (70%) by
LiBH4 reduction (Scheme 4). Benzylation of 17 with BnBr=NaH yielded
18 (85%) and following formylation with n-BuLi=N-formylpiperidine
gave 19 in 70% yield. Finally, debenzylation of 19 with H2=Pd-C caused
deformylation; however, debenzylation with BCl3 gave XH-14 (1) in 90%
yield, and the spectroscopic data were confirmed by literature.[6]
In conclusion, the most practical and optimized nine step reaction
procedures including regioselective iodination, methylation, Sonogashira

Total Synthesis of XH-14
509
Scheme 2. Sonogashira coupling reactions.
coupling, iodine-induced cyclization, Wittig reaction, reduction, benzyla-
tion, formylation, and debenzylation gave XH-14 (1) in 23% overall yield
from vanillin. XH-14 is now under investigation for biological activities.
Scheme 3. Halogen-induced cyclization.

510
H. B. Bang et al.
Scheme 4. Total synthesis of XH-14 from vanillin.
EXPERIMENTAL
All chemicals used were purchased from commercial sources and used as
received unless otherwise stated. NMR spectra were recorded at Varian
Mercury 300-MHz FT-NMR for 1H and 75 MHz for 13C, with the chemical
shifts (d) reported in parts per million (ppm) relative to TMS and the coup-
ling constants (J) quoted in hertz. CDCl3 was used as a solvent and an inter-
nal standard. Infrared (IR) spectra were recorded on a Shimadzu IR-435
spectrometer. Gas chromatography-mass spectrometer (GC-MS) analyses
were performed using a HP-5890=JMS-AM 150, Jeol. Flash chromato-
graphywascarriedoutusingsilicagel, Merck60(230–400mesh). Thin-layer
chromatography (TLC) was performed on DC-Plastikfolien 60, F254
(Merck, layer thickness 0.2 mm) plastic-backed silica-gel plates with visua-
lization by UV light (254 nm) or by treatment with p-anisaldehyde. Melting
points were measured on a Mel-Temp II apparatus and were uncorrected.
4-Hydroxy-3-iodo-5-methoxybenzaldehyde (3b)
To a solution of vanillin (2) (1.00 g, 6.57 mmol) in EtOH (50 mL) under
nitrogen atmosphere, I2 (2.08 g, 7.89 mmol) and silver sulfate (2.46 g,

Total Synthesis of XH-14
511
7.89 mmol) were added and stirred for 1 h at rt. Solvent was removed by
evaporation, and the organic product was extracted with CH2Cl2, washed
with brine, dried, and concentrated to give the solid. The solid was chro-
matographed (EtOAc–Hexane ¼ 1:2) to give the white solid 3b (1.47 g,
80%). Rf 0.34 (EtOAc–Hexane ¼ 1:3); mp 179–181 ꢀC [lit.[8b] mp
ꢀ
1
180 C]; H NMR (300 MHz, CDCl3) d 3.97 (3H, s, OMe), 6.69 (1H, s,
OH), 7.36 (1H, d, J ¼ 1.5 Hz, C6-H), 7.81 (1H, d, J ¼ 1.5 Hz, C2-H),
9.75 (1H, s, CHO). 13C NMR (75 MHz, CDCl3) d 56.8 (OMe), 80.7
(C3-I), 108.8 (C6), 131.2 (C1), 136.4 (C2), 146.6 (C5), 151.5 (C4), 189.7
(C ¼ O).
3-Iodo-4,5-dimethoxybenzaldehyde (10b)
To a solution of 3b (1.05 g, 3.78 mmol) in CH2Cl2 (50 mL), aqueous
NaOH solution (1.93 g in 30 mL of water) and TBAI (2.09 g, 5.66 mmol)
mmol) were added and stirred until clear. Methyl iodide (2.8 mL,
45.8 mmol) was added to the reaction mixture and stirred for 12 h at rt.
The reaction was quenched with 6N HCl, and the organic product was
extracted with CH2Cl2, washed with brine, dried, and concentrated to
give the solid. The solid was chromatographed (EtOAc–Hexane ¼ 1:4)
to give the white solid 10b (1.07 g, 97%). Rf 0.78 (EtOAc–Hexane ¼ 1:3);
1:3); mp 58–60 ꢀC; 1H NMR (300 MHz, CDCl3) d 3.91 (3H, s, OMe), 3.92
(3H, s, OMe), 7.39 (1H, d, J ¼ 1.8 Hz, C6-H), 7.83 (1H, d, J ¼ 1.5 Hz, C2-
H), 9.81 (1H, s, CHO). 13C NMR (75 MHz, CDCl3) d 56.4 (OMe), 61.0
(OMe), 92.4 (C3-I), 111.3 (C6), 134.1 (C1), 134.9 (C2), 153.1 (C5), 154.3
(C4), 189.8 (C ¼ O).
3-(4-Benzyloxy-3-methoxyphenylethynyl)-4,5-
dimethoxybenzaldehyde (12)
To a solution of 10b (0.59 g, 2.03 mmol), PdCl2(PPh3)2 (0.014 g,
0.02 mmol),
4-benzyloxy-3-methoxyphenylacethylene
(11,
0.72 g,
3.04 mmol), and CuI (0.008 g, 0.04 mmol) in DMF (10 mL) under nitro-
gen atmosphere, Et3N (0.56 mL, 4.05 mmol) was added and stirred for
15 h at rt. The organic product was extracted with CH2Cl2, washed with
brine, dried, and concentrated to give the solid. The solid was chromato-
graphed (EtOAc–hexane ¼ 1:4) to give the yellow solid 12 (0.72 g, 89%).
Rf 0.38 (EtOAc–hexane ¼ 1:3); mp 110–113 ꢀC; 1H NMR (300 MHz,
CDCl3) d 3.91 (3H, s, OMe), 3.93 (3H, s, OMe), 4.10 (3H, s, OMe),
5.18 (2H, s, OCH2Ph), 6.85 (1H, d, J ¼ 8.1 Hz, C50-H), 7.06 (1H, s,
C20-H), 7.02 (1H, dd, J ¼ 1.2 8.4 Hz, C60-H), 7.24–7.44 (6H, m), 7.57
(1H, d, J ¼ 1.5 Hz, C2-H), 9.85 (1H, s, CHO). 13C NMR(75 MHz,

512
H. B. Bang et al.
CDCl3) d 56.3 (OMe), 56.4 (OMe), 61.5 (OMe), 71.2 (OCH2Ph), 83.3
(acethylene C), 95.1 (acethylene C), 110.2 (C3), 113.8 (C6), 114.9 (C50),
115.7 (C10), 118.1 (C20), 125.1 (C60), 127.4 (ꢁ2), 128.2 (benzyl-C4),
128.8 (ꢁ2), 130.0 (C1), 132.2 (C2), 136.8 (benzyl-C1), 149.1 (C40), 149.5
(C30), 153.3 (C5), 155.4 (C4), 190.7 (CHO).
2-(4-Benzyloxy-3-methoxyphenyl)-3-iodo-7-methoxybenzofuran-5-
carbaldehyde (15b)
To a solution of 12 (0.030 g, 0.074 mmol) in CH2Cl2 (3 mL), I2 (0.038 g,
0.149 mmol) was added and stirred for 2 h at rt. The organic product
was extracted with CH2Cl2, washed with brine, dried, and concentrated
to give the solid. The solid was chromatographed (EtOAc–hexane ¼ 1:3)
1:3) to give the white solid 15b (0.036 g, 95%). Rf 0.43 (EtOAc–
ꢀ
1
hexane ¼ 1:3); mp 138–140 C; H NMR (300 MHz, CDCl3) d 4.00 (3H,
s), 4.07 (3H, s), 5.22 (2H, s), 6.98 (1H, d, J ¼ 8.1 Hz, C50-H), 7.28–7.46
(6H, m), 7.55 (1H, d, J ¼ 1.2 Hz, C60-H), 7.70 (1H, dd, J ¼ 1.8 Hz,
8.1 Hz, C60-H), 7.72 (1H, d, J ¼ 2.1 Hz, C4-H), 10.03 (1H, s). 13C
NMR(75 MHz, CDCl3) d 56.6, 56.7, 60.1 (C3-I), 71.2 (OCH2), 105.6
(C6), 111.4 (C20), 113.7 (C4), 119.8 (C50), 121.1 (C60), 122.4 (C10),
127.5 (ꢁ2), 128.2 (benzyl-C4), 128.8 (ꢁ2), 133.7 (C5), 134.7 (C3a),
136.8 (benzyl-C1), 145.9 (C40), 146.9 (C30), 149.6 (C7), 149.7 (C7a),
155.1 (C2), 191.5 (C ¼ O).
(E)-2-(4-Benzyloxy-3-methoxyphenyl)-3-iodo-7-methoxy-5-carbethoxy
Ethenylbenzofuran (16)
To a solution of 15b (0.064 g, 0.12 mmol) in CH2Cl2 (10 mL) under nitro-
gen atmosphere, (carbethoxymethylene)triphenylphosphorane (0.068 g,
0.19 mmol) was added and refluxed for 6 h. The organic product was
extracted with CH2Cl2, washed with brine, dried, and concentrated to
give the solid. The solid was chromatographed (EtOAc–hexane ¼ 1:4)
to give the white solid 16 (0.067 g, 93%). Rf 0.44 (EtOAc–hexane ¼ 1:3);
1:3); mp 165–167 ꢀC; 1H NMR (300 MHz, CDCl3) d 1.36 (3H, t,
J ¼ 7.2 Hz, CH3), 3.99 (3H, s), 4.04 (3H, s), 4.28 (2H, q, J ¼ 7.2 Hz,
OCH2), 5.22 (2H, s), 6.45 (1H, d, J ¼ 15.9 Hz, trans ethenyl C1-H),
6.96 (1H, d, J ¼ 8.7 Hz), 7.01 (1H, d, J ¼ 1 Hz), 7.19 (1H, d, J ¼ 1 Hz),
7.28–7.46 (5H, m) 7.68 (1H, dd, J ¼ 1.8 Hz 8.1 Hz), 7.71 (1H, d,
J ¼ 1.8 Hz), 7.77 (1H, d, J ¼ 15.6 Hz trans ethenyl C2-H). 13C NMR
(75 MHz, CDCl3) d 14.7 (CH3), 56.5 (OCH3), 56.6 (OCH3), 60.0
(C3-I), 60.8 (OCH2), 71.2 (OCH2), 106.9, 111.4, 113.7, 115.0, 117.9 (trans

Total Synthesis of XH-14
513
ethenyl-C1), 121.1, 122.8, 127.5 (ꢁ2), 128.2, 128.8 (ꢁ2), 131.2, 134.7,
136.9, 144.5 (trans ethenyl-C2), 145.0, 145.3, 149.5, 154.4, 167.1 (C ¼ O).
2-(4-Benzyloxy-3-methoxyphenyl)-3-iodo-5-(3-hydroxypropyl)-7-
methoxybenzofuran (17)
LiBH4 (2.0M, 0.38 mL) was added to a solution of 16 (0.089 g, 0.15 mmol)
in THF (10 mL) under nitrogen atmosphere and stirred for 24 h at rt. The
organic product was extracted with CH2Cl2, washed with brine, dried,
and concentrated to give the solid. The solid was chromatographed
(EtOAc–hexane ¼ 1:1) to give the white solid 17 (0.057 g, 70%). Rf 0.45
ꢀ
1
(EtOAc–hexane ¼ 1:1); mp 112–115 C; H NMR (300 MHz, CDCl3) d
1.96 (2H, m, propyl C2-H), 2.81 (2H, t, J ¼ 6.9 Hz, propyl C1-H), 3.71
(2H, t, J ¼ 6.3 Hz, propyl C3-H), 3.98 (3H, s), 4.01 (3H, s), 5.20 (2H,
s), 6.70 (1H, s), 6.83 (1H, s), 6.95 (1H, d, J ¼ 8.4 Hz), 7.28–7.45 (5H,
m) 7.67 (1H, dd, J ¼ 1.8 Hz, 8.1 Hz), 7.71 (1H, d, J ¼ 1.8 Hz). 13C
NMR (75 MHz, CDCl3) d 32.8 (propyl C2-H), 35.0 (propyl C1-H),
56.5 (OCH3), 56.6 (OCH3), 60.3 (C3-I), 62.6 (OCH2), 71.2 (OCH2Ph),
108.8, 111.5, 113.2, 113.7, 120.9, 123.3, 127.5 (ꢁ2), 128.1, 128.3, 128.8
(ꢁ2), 134.3, 137.0, 138.3, 144.8, 149.2, 149.5, 153.6.
2-(4-Benzyloxy-3-methoxyphenyl)-3-iodo-5-(3-benzyloxypropyl)-7-
methoxybenzofuran (18)
To a solution of 17 (0.023 g, 0.04 mmol) in THF (5 mL) under nitrogen
atmosphere, NaH (0.005 g, 0.13 mmol) and BnBr (0.01 mL, 0.06 mmol)
were added and refluxed for 7 h. After the solution was filtered using
Celite1, the solvent was removed by evaporation and the organic
product was extracted with CH2Cl2, washed with brine, dried, and con-
centrated to give the solid. The solid was chromatographed (EtOAc–
hexane ¼ 1:3) to give the white solid 18 (0.022 g, 85%). Rf 0.76
ꢀ
1
(EtOAc–hexane ¼ 1:2); mp 100–102 C; H NMR (300 MHz, CDCl3) d
2.02 (2H, m), 2.84 (2H, t, J ¼ 7.5 Hz), 3.54 (2H, t, J ¼ 6.3 Hz), 3.99
(3H, s), 4.00 (3H, s), 4.54 (2H, s, benzyl-CH2), 5.23 (2H, s, benzyl-
CH2), 6.70 (1H, s), 6.85 (1H, s), 6.96 (1H, d, J ¼ 8.4 Hz), 7.28–7.45
(10H, m), 7.69 (1H, dd, J ¼ 1.8 Hz, 8.1 Hz), 7.72 (1H, d, J ¼ 1.8 Hz).
13C NMR (75 MHz, CDCl3) d 32.3, 33.2, 56.5 (OCH3), 56.6 (OCH3),
60.3 (C3-I), 69.8 (OCH2), 71.2 (OCH2Ph), 73.3 (OCH2Ph), 108.7,
111.3, 113.3, 113.6, 120.9, 123.3, 127.5 (ꢁ2), 127.8, 127.9 (ꢁ2), 128.0,
128.2, 128.6 (ꢁ2), 128.7, 128.8 (ꢁ2), 134.2, 136.9, 138.4, 144.7, 149.1,
149.4, 153.5.

514
H. B. Bang et al.
2-(4-Benzyloxy-3-methoxyphenyl)-5-(3-benzyloxypropyl)-7-
Methoxybenzofuran-3-carbaldehyde (19)
To a solution of 18 (0.05 g, 0.08 mmol) in toluene (5 mL) under a nitrogen
atmosphere, N-formylpiperidine (0.09 mL, 0.79 mmol) and n-BuLi
(0.5 mL, 1.6 M in hexane) were added and stirred for 0.5 h at 0 ꢀC. After
the solution was neutralized with 1 N HCl, the organic product was
extracted with diethyl ether, washed with brine, dried, and concentrated
to give the solid. The solid was chromatographed (EtOAc–hexane ¼ 1:4)
to give the white solid 19 (0.03 g, 70%). Rf 0.47 (EtOAc–hexane ¼ 1:2);
ꢀ
1
mp 70–72 C; H NMR (300 MHz, CDCl3) d 2.00 (2H, m), 2.83 (2H, t,
J ¼ 8.1 Hz), 3.52 (2H, t, J ¼ 6.3 Hz), 3.98 (3H, s), 3.99 (3H, s), 4.52
(2H, s), 5.24 (2H, s), 6.72 (1H, d, J ¼ 1.2 Hz), 7.00 (1H, d, J ¼ 8.4 Hz),
7.25–7.47 (12H, m), 7.65 (1H, s), 10.26 (1H, s, CHO). 13C NMR
(75 MHz, CDCl3) d 32.3, 33.3, 56.4 (OCH3), 56.6 (OCH3), 69.9
(OCH2), 71.2, 73.3, 109.1, 112.1, 113.7, 113.8, 117.1, 121.7, 123.0,
127.4, 127.5 (ꢁ2), 127.7, 127.9 (ꢁ2), 128.3, 128.6 (ꢁ2), 128.9 (ꢁ2),
136.5, 138.7, 140.3, 141.8, 144.7, 150.0, 150.9, 165.9, 186.9 (CHO).
XH-14 (1)
BCl3 (0.11 mL, 1.0 M in CH2Cl2) was added to a solution of 19 (0.03 g,
0.06 mmol) in CH2Cl2 (5 mL) under nitrogen atmosphere and stirred
for 1 h at ꢂ78 ꢀC. The organic product was extracted with CH2Cl2,
washed with brine, dried, and concentrated to give the solid. The solid
was chromatographed (MeOH–CHCl3 ¼ 1:15) to give the yellow solid 1
(0.017 g, 90%). Rf 0.31 (MeOH–CHCl3 ¼ 1:15); mp 77–79 ꢀC (lit.[6] mp
ꢀ
1
77–79 C); H NMR(300 MHz, CD3OD) d 1.89 (2H, m, propyl C2-H),
2.75 (2H, t, J ¼ 8.4 Hz, propyl C1-H), 3.59 (2H, t, J ¼ 6.6 Hz, CH2OH),
3.95 (3H, s, C30-OCH3), 3.97 (3H, s, C7-OCH3), 6.79 (1H, d, J ¼ 1.2 Hz,
C6-H), 6.94 (1H, d, J ¼ 8.1 Hz C50-H), 7.33 (1H, dd, J ¼ 1.8 Hz 8.4 Hz,
C60-H), 7.41 (1H, d, J ¼ 2.1 Hz, C20-H), 7.50 (1H, d, J ¼ 1.2 Hz, C4-H),
10.16 (1H, s, CHO). 13C NMR(75 MHz, CD3OD) d 32.5 (propyl C2),
34.8 (propyl C1), 55.4 (C30-OCH3), 55.5 (C5-OCH3), 61.1 (CH2OH),
108.7 (C6), 111.7 (C4), 113.0 (C20), 115.6 (C50), 116.1 (C3a), 120.0
(C60), 123.2 (C10), 127.2 (C5), 140.2 (C3), 141.5 (C7a), 144.7 (C7),
148.2 (C40), 150.0 (C30), 166.3 (C2), 187.0 (CHO).
ACKNOWLEDGMENTS
This work was supported by the Ministry of Commerce, Industry, and
Energy, through the Center for Efficacy Assessment and Development

Total Synthesis of XH-14
515
of Functional Foods and Drugs at Hallym University, and in part by
Grant No. R01-2007-000-20164-0 from the Basic Research Program of
Korea Science and Engineering Foundation.
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1. Chang, H. M.; Cheng, K. P.; Choang, T. F.; Chow, H. F.; Chui, K. Y.; Hon,
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C. F.; Cui, Y. X.; Wong, H. N. C. Structure elucidation and total synthesis of
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