Trifluoroacetic acid-mediated facile transformation of 2-C-hydroxymethyl-d-glycals to chiral pyrano[2,3-b]benzopyrans

Article abstract of DOI:10.1016/j.carres.2008.12.020

Treatment of 2-C-hydroxymethyl-d-glycals with phenols in trifluoroacetic acid at ambient temperature leads to an extremely facile transformation affording chiral pyrano[2,3-b]benzopyrans in high yields.

Full text of DOI:10.1016/j.carres.2008.12.020

Carbohydrate Research 344 (2009) 521–525
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Trifluoroacetic acid-mediated facile transformation of 2-C-
hydroxymethyl-D-glycals to chiral pyrano[2,3-b]benzopyrans
*
Meenakshisundaram Santhi, Kalpattu K Balasubramanian, Shanmugasundaram Bhagavathy
Shasun Research Centre, 27, Vandaloor Kelambakkam Road, Keelakottaiyur Village, Melakottaiyur post, Chennai 600 048, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Treatment of 2-C-hydroxymethyl-
D
-glycals with phenols in trifluoroacetic acid at ambient temperature
Received 12 September 2008
Received in revised form 22 December 2008
Accepted 23 December 2008
Available online 31 December 2008
leads to an extremely facile transformation affording chiral pyrano[2,3-b]benzopyrans in high yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Ferrier rearrangement
Pyranobenzopyrans
Trifluoroacetic acid
2-C-Hydroxymethyl-
D-glycal
Intramolecular cyclization
Benzopyrans, an important class of oxygenated heterocycles,
constitute the core skeleton of many complex natural products.1,2
In general, most of the benzopyran derivatives are synthesized by
condensation of salicylaldehyde or its derivatives with various con-
jugated olefins.3–8 Booma and Balasubramanian reported the syn-
thesis of fused chiral pyrano[2,3-b]benzopyrans from the reaction
catalyzed by TFA at ambient temperature in good-to-excellent
yields without prior activation of the allylic hydroxyl group.
The key glycals 1–4 were synthesized as reported in the litera-
ture starting from tri-O-acetyl-
cresol 5a with TFA at ambient temperature led to an instantaneous
reaction that resulted in the formation of the -pyrano[2,3-b]benz-
D
-glycals.22–25 Exposure of 1 and p-
a
of 3,4,6-tri-O-protected 2-C-acetoxymethyl-
D
-glycals with phenols
opyran 6a as the major product and b-pyrano[2,3-b]benzopyran
10a as the minor product (Scheme 1), in 94% yield (Table 1, entry
1). The reaction was also equally facile in the case of the reaction
of other 2-C-hydroxymethylglycals 2–4 with p-cresol. The general-
ity of this transformation has been successfully tested on glycals 1–
4 using p-cresol 5a, p-methoxyphenol 5b (Scheme 1) and b-naph-
thol 5c (Scheme 2). We observe that in the case of glucals 1 and 3,
in the presence of BF3ꢀEt2O.9 Yadav et al. described the synthesis of
3,4-dihydro-2H-1-benzopyrans from the reaction of 3,4-dihydro-
2H-pyrans and salicylaldehydes.10 Since then, only a few reports
have appeared in the literature on the use of other catalysts for
effectingthistransformation.11,12 Asurveyof theliteratureindicated
that the Ferrier rearrangement has been carried out mostly on pro-
tected glycals, such as allylic acetates of glycals, and not directly
on glycals with free allylic-OH groups, indicating that prior activa-
tion of the allylic hydroxyl group is necessary for realizing the Ferrier
rearrangement.13,14 However, there are a few examples of trifluoro-
acetic acid (TFA) and trifluoromethanesulfonic acid-catalyzed Ferri-
er rearrangements involving the unactivated allylic hydroxyl group
of exocyclicandendocyclicglycals.15,16 TFAis knowntomediatevar-
ious types of glycosidation, addition and cyclization reactions,17–21
and to our knowledge, the transformation of 2-C-hydroxymethyl
or 2-C-acetoxymethylglycals to pyranobenzopyrans with phenols
using TFA has not yet been investigated.
the
the minor product (Table 1, entries 1–3 and 7–9). In the case of
galactals 2 and 4, the anomer is almost the exclusive product (Ta-
a anomer was found to be the major product and the b anomer
a
ble 1, entries 4–6 and 10–12). All the pyrano [2,3-b]benzopyrans
listed in Table 1 were characterized by NMR spectroscopy, and
all are in accord with those reported in the literature.9,11,12 The
assignments of
a and b configurations were based on NOE experi-
ments and also on the comparison of the NMR spectral data with
those reported in the literature.9,12 The regioselectivity of phenol
addition was based on earlier literature reports of these products
and also on the NMR chemical shifts of the anomeric protons.9
The exact mechanism of this transformation is unknown.
Herein, we report on an extremely facile transformation of 2-C-
hydroxymethyl-
D
-glycals 1–4 to chiral pyrano[2,3-b]benzopyrans
It is of interest to note that, unlike the electron-donating phe-
nols, the reaction of glycals 1–4 with p-nitrophenol as the nucleo-
phile did not afford any clean product. As acetic acid is relatively
weaker as an acid and is cheaper than TFA, we explored the Ferrier
* Corresponding author. Tel.: +91 44 27476229; fax: +91 44 27476190.
E-mail address: bhagavathy@shasun.com (S. Bhagavathy).
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.12.020

522
M. Santhi et al. / Carbohydrate Research 344 (2009) 521–525
OR
H
O
O
R2
R3
R2 OR
OH
R1
R1
RO
6 a,b 9 a,b
)
O
TFA
(
)- (
+
rt, 1-3 min.
+
R3
OR
H
OH
1-4
O
O
5a,b
3
R2
5a
R3
R = Me
5b R3 = OMe
R1
10(a,b)-13(a,b)
6a, 10a R1 = OMe, R2 = H, R = Me, R3 = Me
1 R1 = OMe, R2 = H, R = Me
2 R1 = H, R2 = OMe, R = Me
3 R1 = OBn, R2 = H, R = Bn
1
2
3
6b 10b
,
R = OMe, R = H, R = Me, R = OMe
1
2
3
7a 11a
,
R = H, R = OMe, R = Me, R = Me
1
2
3
1
2
7b 11b
,
R = H, R = OMe, R = Me, R = OMe
4
R = H, R = OBn, R = Bn
8a, 12a R1 = OBn, R2 = H, R = Bn, R3 = Me
8b, 12b R1 = OBn, R2 = H, R = Bn, R3 = OMe
9a 13a
,
R1 = H, R2 = OBn, R = Bn, R3 = Me
1
2
3
9b 13b
,
R = H, R = OBn, R = Bn, R = OMe
Scheme 1. Synthesis of chiral pyranobenzopyrans.
rearrangement of glycals 1–4 with p-cresol 5a using acetic acid sol-
vent. Surprisingly, it did not lead to any product formation, even
after a 48-h reaction time.
In conclusion, TFA is found to be a versatile reagent for the facile
conversion of 2-C-hydroxylmethylglycals with phenols to chiral
pyrano[2,3-b]benzopyrans without the need for prior activation
of the allylic hydroxyl group of glycals as acetates.
Specific optical rotations were recorded on Autopol-V80000 instru-
ment. IR spectra were recorded on a Perkin–Elmer instrument.
High-resolution mass spectra (HRESIMS) were recorded on a
QSTAR instrument. Melting points were determined on a Veego
(VMP-PM) apparatus and are uncorrected. In the case of glucals,
a
and b anomers could not be separated by column chromatogra-
phy. However, the anomer could be obtained by repeated crys-
tallization of the mixture. In the case of galactals, the anomer
a
a
was the major product, and it was isolated by column chromatog-
raphy. All the new compounds were thoroughly characterized by
NMR, HSQC and NOE experiments. For TLC analysis, the solvent
system used was 7:3 hexane–EtOAc.
1. Experimental
1.1. General
Trifluoroacetic acid purchased from Sigma–Aldrich was used di-
rectly without further purification. All solvents used for workup
were purchased from commercial sources. All TFA reactions were
carried out in open glass flasks. NMR spectra were recorded on
Bruker DPX-300 (300 MHz) in CDCl3 containing trimethylsilane.
1.2. General experimental procedure
To a solution of 2-C-hydroxymethyl-
and phenol 5a–c (0.8 mmol) was added TFA (2 mL), and the mix-
D-glucal 1–4 (0.4 mmol)
Table 1
TFA mediated synthesis of pyrano[2,3-b]pyrans
Entry
Glycal
Phenol
Product (s) (
a
and b)
Yielda (%)
Ratiob
(a:b)
1
2
3
4
5
6
7
8
9
1
1
1
2
2
2
3
3
3
4
4
4
p-Cresol
6a and 10a
6b and 10b
14 and 18
7a and 11a
7b and 11b
15 and 19
8a and 12a
8b and 12b
16 and 20
9a and 13a
9b and 13b
17 and 21
94
81
96
94
88
94
94
96
97
93
94
92
2.5:1
3.5:1
3.5:1
ꢁ95%
ꢁ98%
ꢁ98%
p-Methoxyphenol
b-Naphthol
p-Cresol
p-Methoxyphenol
b-Naphthol
p-Cresol
p-Methoxyphenol
b-Naphthol
p-Cresol
p-Methoxyphenol
b-Naphthol
a
a
a
2.1: 0.9
3: 2
3:1.5
ꢁ95%
ꢁ98%
ꢁ98%
10
11
12
a
a
a
a
Isolated yields after column chromatography.
b
Determined by relative integration of proton H-10a/H-12a in glucal series and H-4 proton in galactal series in the 1H NMR spectrum of the crude product.

M. Santhi et al. / Carbohydrate Research 344 (2009) 521–525
523
OR
H
O
O
R2
R1
OR
R2
R1
RO
O
OH
TFA
14-17
+
+
r.t, 1-3 min.
OR
OH
H
O
1-4
5c
O
1, 14, 18 R1 = OMe, R2 = H, R = Me
2, 15, 19
3, 16, 20
4, 17, 21
R2
R1 = H, R2 = OMe, R = Me
R1=OBn, R2 = H, R = Bn
R1 =H, R2 = OBn, R = Bn
R1
18-21
Scheme 2. Synthesis of pyranonaphthopyrans.
ture was stirred at rt for 1–3 min. The reaction was monitored by
TLC (and can also be monitored by 1H NMR spectrum with TFA-
d). The reaction mixture was diluted with H2O (10 mL) and ex-
tracted with EtOAc (3 ꢂ 10 mL). The organic layer was washed
with 10% NaOH (2 ꢂ 5 mL), followed by brine (5 mL), dried over
anhyd Na2SO4 and concentrated under vacuum. The crude product
was purified by flash column chromatography on silica gel (230–
400 mesh) using hexane–EtOAc as the eluant.
7.78 (m, 2H, H-6, H-9); 13C NMR: d 30.38 (t, C-5), 56.71, 59.49
(2q, 2ꢂOCH3), 71.14 (t, C-20), 71.80 (d, C-2), 72.19 (d, C-3), 93.65
(d, C-12a), 112.75 (s, C-4a), 119.03, 121.83, 123.63 (d, arom.CH),
123.69 (d, C-4), 126.63, 128.34, 128.50 (3d, arom.CH), 129.20,
130.50, 132.18, 151.20 (4s, arom.C).
1.2.4. (2R,3R,10aR)-3,10a-Dihydro-2-methoxymethyl-3-
methoxy-7-methy1-2H,5H-pyrano[2,3-b][1]benzopyran (7a)
Mp 84–86 °C; Rf: 0.55; ½a D25
ꢃ
ꢄ175.2° (c 0.4, CHCl3); 1H NMR: d
1.2.1. (2R,3S,10aR)-3,10a-Dihydro-2-methoxymethyl-3-
methoxy-7-methy1-2H,5H-pyrano[2,3-b][1]benzopyran (6a)11
Mp 107–108 °C (lit.11 107 °C); Rf: 0.38; 1H NMR (d): 2.24 (s, 3H,
CH3), 3.35 (br d, J = 18 Hz, 1H, H-5A), 3.42 (s, 3H, OCH3), 3.46 (s, 3H,
OCH3), 3.66–3.76 (m, 3H, H-5B, H-20), 3.85 (dt, J = 3.0, 9.0 Hz, 1H,
H-2), 4.01 (dd, J = 3.0, 9.0 Hz, 1H, H-3), 5.5 (s, 1H, H-10a), 6.00 (s,
1H, H-4), 6.78–6.92 (m, 3H, arom.H); 13C NMR (d): 20.46 (q, CH3),
32.97 (t, C-5), 56.68, 59.47 (2q, OCH3), 71.12 (t, C-20), 71.57,
72.12 (2d, C-2, C-3), 93.61 (d, C-10a), 117.02 (d, C-4), 120.61 (s,
C-4a), 123.09, 128.23, 128.91 (3d, arom.CH), 130.38, 130.66,
151.40 (3s, arom.C).
2.24 (s, 3H, CH3), 3.43, 3.45 (2s, 6H, 2 ꢂ OCH3), 3.37 (d, J = 18 Hz,
1H, H-5A), 3.63 (dd, J = 2.0, 5.6 Hz, 1H, H-3), 3.70 (br d, J ꢁ 6.0 Hz,
2H, H-20), 3.75 (d, J = 18 Hz, 1H, H-5B), 4.17 (td, J = 2.4, 6.0 Hz, 1H,
H-2), 5.57 (s, 1H, H-10a), 6.18 (dd, J = 2.4, 6.0 Hz, 1H, H-4), 6.80 (d,
J = 8.4 Hz, 1H, H-9), 6.84 (br s, 1H, H-6), 6.90 (d, J = 8.0 Hz, 1H, H-8);
13C NMR: d 20.47 (q, CH3), 33.56 (t, C-5), 56.85, 59.33 (2q,
2 ꢂ OCH3), 69.66, 71.52 (2d, C-2, C-3), 71.48 (t, C-20), 93.39 (d, C-
10a), 120.58 (s, C-4a), 117.11, 119.21, 128.33, 128.94 (4d, C-4,
3 ꢂ arom.CH), 120.58, 130.50, 135.16, 151.32 (4s, C-4a, arom.C);
IR (neat, cmꢄ1): 2912, 2886, 1577, 1491, 1450, 1380, 1210, 1190,
1050, 980; HRESIMS: Calcd for [C16H20O4+Na]: 299.1259,
found:299.1259.
1.2.2. (2R,3S,10aR)-3,10a-Dihydro-2-methoxymethyl-3-
methoxy-7-methoxy-2H,5H-pyrano[2,3-b][1]benzopyran (6b)
1.2.5. (2R,3R,10aR)-3,10a-Dihydro-2-methoxymethyl-3-
methoxy-7-methoxy-2H,5H-pyrano[2,3-b][1]benzopyran (7b)
Mp 94–95 °C; Rf: 0.28; ½a D28
ꢃ
ꢄ140.39° (c 0.84, CH2Cl2); 1H NMR:
d 3.37 (d, J = 18.0 Hz, 1H, H-5A), 3.43, 3.46 (2s, 6H, 2 ꢂ OCH3), 3.67–
3.76 (m, 6H, H-5B, H-20, OCH3), 3.85 (td, J = 3.0, 9.0 Hz, 1H, H-2),
4.01 (dd, J = 6.0, 9.0 Hz, 1H, H-3), 5.48 (s, 1H, H-10a), 6.01 (br s,
1H, H-4), 6.56 (d, J = 3.0 Hz, 1H, H-6), 6.69 (dd, J = 3.0, 9.0 Hz, 1H,
H-8), 6.82 (d, J = 9.0 Hz, 1H, H-9); 13C NMR: d 33.19 (t, C-5),
55.73, 56.72, 59.47 (3q, 3 ꢂ OCH3), 71.13 (t, C-20), 71.61 (d, C-2),
72.14 (d, C-3), 93.57 (d, C-10a), 113.12, 113.66, 117.93 (3d, ar-
om.CH), 121.54 (s, C-4a), 123.24 (d, C-4), 130.57, 147.61, 154.00
(3s, arom.C); IR (KBr, cmꢄ1): 2994, 2921, 2833, 1592, 1500, 1435,
1393, 1268, 1108, 956, 923; ESIMS (m/z): 315.12 [M+Na], 261.11
[MꢄOCH3]; HRESIMS: Calcd for [C16H20O5+Na]: 315.1208, found:
315.1213.
Mp 67–68 °C; Rf: 0.32; ½a D25
ꢃ
ꢄ380.5° (c 0.55, CH2Cl2); 1H NMR: d
3.39 (d, J = 18 Hz, 1H, H-5A), 3.43, 3.45 (2s, 6H, 2 ꢂ OCH3), 3.63 (dd,
J = 2.3, 5.7 Hz, 1H, H-3), 3.70 (br d, J = 6.3 Hz, 2H, H-20), 3.74 (s, 3H,
OCH3), 3.81 (d, J = 18 Hz, 1H, H-5B), 4.18 (td, J = 2.3, 6.6 Hz, 1H, H-
2), 5.56 (s, 1H, H-10a), 6.19 (dd, J = 1.8, 5.7 Hz, 1H, H-4), 6.58 (d,
J = 1.8 Hz, 1H, H-6), 6.69 (dd, J = 2.7, 9.0 Hz, 1H, H-8), 6.84 (d,
J = 9.0 Hz, 1H, H-9); 13C NMR: d 33.79 (t, C-5), 55.75, 56.88, 59.32
(3q, OCH3), 69.68 (d, C-3), 71.53 (t, C-20), 71.55 (d, C-2), 93.40 (d,
C-10a), 113.16, 113.79, 118.05 (3d, arom.CH), 119.38 (d, C-4),
121.52, 135.08, 147.57, 154.08 (4s, C-4a, arom.C); IR (neat,
cmꢄ1): 3054, 2985, 2832, 1494, 1429, 1212, 1094, 1039, 959; HRE-
SIMS: Calcd for [C16H20O5+Na]: 315.1208, found: 315.1203.
1.2.3. (2R,3S,12aR)-2,3,5,12a-Tetrahydro-2-methoxymethyl-3-
methoxy-[2,3-b]naphtho[1,2-e]pyran (14)12
1.2.6. (2R,3R,12aR)-2,3,5,12a-Tetrahydro-2-methoxymethyl-3-
methoxy-[2,3-b]naphtho[1,2-e]pyran (15)12
Mp 199–200 °C (lit.12 201 °C); Rf: 0.41; 1H NMR: d 3.45, 3.49 (2s,
6H, 2 ꢂ OCH3), 3.73–3.77 (m, 2H, H-20), 3.78–3.81 (m, 1H, H-5A),
3.91–3.97 (m, 2H, H-5B, H-2), 4.07 (dd, J = 3.3, 9.2 Hz, 1H, H-3),
5.62 (s, 1H, H-12a), 6.13 (s, 1H, H-4), 7.12, 7.64 (2d, J = 8.9 Hz,
2H, H-10, H-11), 7.36, 7.50 (2t, J = 7.5 Hz, 2H, H-7, H-8), 7.72–
Mp 93–94 °C (lit.12 91 °C); Rf: 0.47; 1H NMR: d 3.46, 3.47 (2s, 6H,
2 ꢂ OCH3), 3.66 (dd, J = 2.1, 5.8 Hz, H-3), 3.71–3.80 (m, 3H, H-5A,
H-5B, H-20A), 3.97 (d, J = 18.0 Hz, 1H, H-20B), 4.24 (dt, J = 2.1,
6.0 Hz, 1H, H-2), 5.70 (s, 1H, H-12a), 6.30 (dd, J = 2.1, 5.7 Hz, 1H,
H-4), 7.13, 7.63 (2d, J = 9.0 Hz, 2H, H-10, H-11), 7.36, 7.51 (2dd,

524
M. Santhi et al. / Carbohydrate Research 344 (2009) 521–525
J = 2.1, 8.3 Hz, 2H, H-6, H-9), 7.70–7.77 (m, 2H, H-7, H-8); 13C NMR:
d 3.96 (t, C-5), 56.90, 59.35 (2q, 2 ꢂ OCH3), 69.70, 71.70 (2d, C-2, C-
3), 71.59 (t, C-20), 93.50 (d, C-12a), 112.72 (s, C-4a), 119.05, 119.74,
121.80, 123.76, 126.70, 128.42, 128.53 (7d, arom.CH), 129.23,
132.18, 135.05, 151.20 (4s, arom.C).
73.54 (t, CH2), 93.48 (d, C-10a), 117.05 (d, arom.C), 119.80 (d, C-
4), 120.64 (s, C-4a), 127.66, 127.33, 127.82, 127.86, 128.31,
128.38, 128.95, 129.98 (8d, arom.C), 130.47, 134.74, 138.08,
138.33, 151.32 (5s, arom.C); IR (KBr, cmꢄ1): 3040, 2886, 1600,
1588, 1485, 1390, 1360, 1335, 1180, 1085, 950, 825; ESIMS (m/
z): 451.18 [M+Na], 429.5 [M+H], 321.15 [MꢄOBn]; HRESIMS: Calcd
for C28H28O4+Na: 451.1885, found: 451.1884.
1.2.7. (2R,3S,10aR)-3,10a-Dihydro-2-benzyloxymethyl-3-
benzyloxy-7-methy1-2H,5H-pyrano[2,3-b][1]benzopyran (8a)9
Mp 84–85 °C; Rf: 0.58; ½a D25
ꢃ
ꢄ81° (c 0.6, CH2Cl2); 1H NMR: d 2.24
1.2.11. (2R,3R,10aR)-3,10a-Dihydro-2-benzyloxymethyl-3-
benzyloxy-7-methy1-2H,5H-pyrano[2,3-b][1]benzopyran (9b)9
(s, 3H, CH3), 3.34 (d, J = 18.0 Hz, 1H, H-5A), 3.68 (br d, J = 18.0 Hz,
1H, H-5B), 3.81 (d, J = 2.1 Hz, 1H, H-20), 3.94 (br d, J = 8.0 Hz, 1H,
H-2), 4.34 (dd, J = 3.0, 6.0 Hz, 1H, H-3), 4.46–4.70 (m, 4H,
2 ꢂ CH2), 5.52 (s, 1H, H-10a), 5.99 (br s, 1H, H-4), 6.77–6.92 (m,
3H, arom.H), 7.23–7.36 (m, 10H, arom.H); 13C NMR: d 20.46 (q,
CH3), 32.97 (t, C-5), 68.22 (d, C-20), 70.37 (d, C-3), 71.38 (t, CH2),
71.89 (d, C-2), 73.55 (t, CH2), 93.67 (d, C-10a), 116.96, 120.60,
127.66, 127.80, 127.97, 128.23, 128.39 (8d, arom.CH), 123.75 (d,
C-4),128.91, 130.36, 130.52, 137.91, 138.09, 151.39 (6s, C-4a,
5ꢂarom.C); IR (CHCl3, cmꢄ1): 3040, 2864, 1605, 1590, 1495,
1390, 1310, 1200, 1170, 1120, 1075, 960, 930.; HRESIMS: Calcd
for [C28H28O4+Na]: 451.1885, found: 451.1887.
Mp 89–90 °C; Rf: 0.52; ½a D25
ꢃ
ꢄ281° (c 1.1, CH2Cl2); 1H NMR: d
3.36 (d, J = 18.0 Hz, 1H, H-5A), 3.74 (s, 3H, OCH3), 3.79–3.89 (m,
4H, H-20, H-5B, H-3), 4.24 (td, J = 2.4, 6.0 Hz, 1H, H-2), 4.65–4.69
(AB quartet, 4H, J = 12.0 Hz, 2 ꢂ CH2), 5.57 (s, 1H, H-10a), 6.08
(dd, J = 2.9 Hz, 1H, H-4), 6.55 (d, J = 2.9 Hz, 1H, H-6), 6.69 (dd,
J = 2.9, 8.1 Hz, 1H, H-8), 6.83 (d, J = 8.1 Hz, 1H, H-9), 7.25–7.39
(m, 10H, arom.H); 13C NMR: d 33.70 (t, C-5), 55.71 (q, OCH3),
67.55 (d, C-3), 68.80 (t, C-20), 71.26 (t, CH2), 71.60 (d, C-2),
73.53 (t, CH2), 93.43 (d, C-10a), 113.12, 113.72, 117.97 (3d, ar-
om.CH), 119.94 (d, C-4), 121.56 (s, C-4a), 127.66, 127.74,
127.79, 127.82, 127.83, 128.37, 128.38 (7d, arom.CH), 134.61,
138.09, 138.32, 147.50, 154.02 (5s, arom.C); IR (KBr, cmꢄ1):
3040, 2885, 1600, 1588, 1485, 1390, 1365, 1330, 1180, 1080,
960, 830; HRESIMS: Calcd for [C28H28O5+Na]: 467.1834, found:
467.1839.
1.2.8. (2R,3S,10aR)-3,10a-Dihydro-2-benzyloxymethyl-3-
benzyloxy-7-methoxy-2H,5H-pyrano[2,3-b][1]benzopyran (8b)9
Mp 102–103 °C; Rf: 0.50; ½a D25
ꢃ
ꢄ83° (c 1.1, CH2Cl2); 1H NMR: d
3.36 (d, J = 18.0 Hz, 1H, H-5A), 3.71 (d, J = 18.0 Hz, 1H, H-5B),
3.73 (s, 3H, OCH3), 3.80 (br d, J = 3.0 Hz, 2H, H-20), 3.94 (dt,
J = 2.1, 9.0 Hz, 1H, H-2), 4.34 (dd, J = 3.0, 9.0 Hz, 1H, H-3), 4.46–
4.70 (m, 4H, 2 ꢂ CH2), 5.50 (s, 1H, H-10a), 5.99 (s, 1H, H-4), 6.55
(d, J = 3.0 Hz, 1H, H-6), 6.69 (dd, J = 2.1, 9.3 Hz, 1H, H-8), 6.80 (d,
J = 9.3 Hz, H-9); 13C NMR: d 33.19 (t, C-5), 55.70 (q, OCH3), 68.21
(t, C-20), 70.37 (d, C-3), 71.42 (t, CH2), 71.91 (d, C-2), 73.55 (t,
CH2), 93.61 (d, H-10a), 113.11, 113.63, 117.87, (3d, arom.CH),
121.53 (s, C-4a), 123.89 (d, C-4), 127.67, 127.82, 127.88, 127.97,
128.39 (5d, arom.C); IR (CHCl3, cmꢄ1): 3040, 2860, 1605, 1590,
1495, 1390, 1365, 1310, 1200, 1170, 1075, 960; HRESIMS: Calcd
for [C28H28O5+Na]: 467.1834, found: 467.1836.
1.2,12. (2R,3R,12aR)-2,3,5,12a-Tetrahydro-2-benzyloxymethyl-
3-benzyloxy-[2,3-b]naphtho[1,2-e]pyran (17)
Rf: 0.61; ½a 2D5
ꢃ
ꢄ254.89° (c 0.45, CH2Cl2); 1H NMR: d 3.73 (d, 1H,
J = 18.0 Hz, H-5A), 3.87–3.97 (m, 4H, H-5B, H-20, H-3), 4.31 (td, 1H,
J = 3.2, 6.0 Hz, 1H, H-2), 4.61 (dd, J = 3.2, 12.0 Hz, 2H, CH2), 4.70 (AB
quartet, J = 12 Hz, 2H, CH2), 5.70 (s, 1H, H-12a), 6.18 (dd, J = 1.5,
6.0 Hz, 1H, H-4), 7.06–7.13 (m, 2H, arom.H), 7.23–7.42 (m, 7H, ar-
om.H), 7.49 (td, J = 1.2, 9.0 Hz, 1H, arom.H) 7.63 (dd, J = 3.0, 9.0 Hz,
2H, arom.H), 7.70–7.77 (m, 4H, arom.H); 13C NMR: d 30.89 (t, C-5),
67.61 (d, C-3), 68.88 (t, C-20), 71.31 (t, CH2), 71.86 (d, C-2), 73.59 (t,
CH2), 93.55 (d, C-12a), 112.77 (s, C-4a), 117.83, 119.00 (2d), 120.29
(d, C-4), 121.82, 123.48, 123.76 (3d, arom.CH), 126.33, 126.43,
126.70, 127.72, 127.82, 127.88, 128.42, 128.53, 128.82, 129.74
(11d, arom.CH), 132.18, 134.62, 138.00, 138.24, 151.13 (5s, ar-
om.C); IR (KBr, cmꢄ1): 3067, 3018, 2855, 1598, 1466, 1397, 1215,
1115, 959, 927; ESIMS (m/z): 487.18 [M+Na], 471.35 [MꢄO+Na],
457.33 [MꢄOꢄCH2+Na]; HRESIMS: Calcd for [C31H28O4+Na]:
487.1885, found: 487.1864.
1.2.9. (2R,3S,12aR)-2,3,5,12a-Tetrahydro-2-benzyloxymethyl-3-
benzyloxy-[2,3-b]naphtho[1,2-e]pyran (16)
Mp 164–165 °C; Rf: 0.61; ½a D25
ꢃ
ꢄ206.6° (c 0.79, CH2Cl2); 1H
NMR: d 3.74 (d, J = 18.0 Hz, 1H, H-5A), 3.85 (d, J = 1.8 Hz, 2H, H-
20), 3.92 (d, J = 18.0 Hz, 1H, H-5B), 4.03 (dt, J = 3.0, 9.0 Hz, 1H, H-
2), 4.40 (dd, J = 3.0, 9.0 Hz, 1H, H-3), 4.49–4.72 (m, 4H, 2 ꢂ CH2),
5.64 (s, 1H, H-10a), 6.12 (br s, 1H, H-4), 7.12, 7.64 (2d, J = 9.0 Hz,
2H, H-10, H-11), 7.27–7.37 (m, 11H, arom.H), 7.50 (br t,
J = 6.0 Hz, 1H, arom.H), 7.71–7.78 (m, 2H, 2 ꢂ arom.H); 13C NMR:
d 30.38 (t, C-5), 68.27 (t, C-20), 70.47 (d, C-3), 71.43 (t, CH2),
72.15 (d, C-2), 73.58 (t, CH2), 93.71 (d, C-12a), 112.76 (s, C-4a),
119.00, 121.84, 123.68 (3d, arom.CH), 124.31 (d, C-4), 126.62,
127.68, 127.83, 127.89, 127.97, 128.40, 128.49 (7d, arom.CH),
129.21, 130.38, 132.20, 137.89, 138.10, 151.21 (6s, arom.C); IR
(KBr, cm-1): 3030, 2902, 1596, 1465, 1391, 1363, 1230, 1176,
1073, 971; HRESIMS: Calcd for [C31H28O4+Na]: 487.1885, found:
487.1884.
Acknowledgements
We are grateful to the management of Shasun Research Centre
(SRC) for providing the facility and encouragement. Our thanks
are due to SRC-QC for analytical data.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2008.12.020.
1.2.10. (2R,3R,10aR)-3,10a-Dihydro-2-benzyloxymethyl-3-
benzyloxy-7-methy1-2H,5H-pyrano[2,3-b][1]benzopyran (9a)9
References
Mp 99–100 °C; Rf: 0.64; ½a D25
ꢃ
ꢄ268° (c 1.1, CH2Cl2); 1H NMR: d
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