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9. Purchased from Tokyo Kasei Kogyo Co.
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Figure 3. Vis spectra and CD of the solution mixed with 9 or 10 with 1
11. To a solution of 6 (1.33 g, 4.7 mmol) in pyridine (20 mL)
was added a solution of 30,40-di-O-acetylcaffeoyl chloride
(1.74 g, 6.17 mmol) in CH2Cl2 at 0 ꢁC and warmed to
30 ꢁC and stood for 3 h. The reaction mixture was added
saturated aqueous NaHCO3 and extracted with CH2Cl2.
The extracts were purified by silica gel chromatography
(hexane–AcOEt 1:1) to afford the corresponding acylated
compound as a white powder (1.67 g, 3.01 mmol, 72%).
The acylated compound (1.55 g, 2.73 mmol) was depro-
tected by treatment with 2 N HCl (3 mL) at 45 ꢁC for 4 h.
To the reaction mixture was added saturated aqueous
NaHCO3 and extracted with AcOEt, then the aqueous
layer was acidified by addition of TFA (6 mL). Compound
2 was extracted with AcOEt (10 mL · 10) and the resulting
crude product was purified by HPLC (Develsil ODS-HG-
5, eluent: aqueous CH3CN) to give 212 (228 mg, 0.64 mmol,
and Al3+ at pH 4.0.
: 9, 0 h,
)
: 10, 0 h,
)
: 9, 2 h,
)
(
(
(
: 10, 2 h.
)
(
we propose a structure of the blue pigment caused by an
Al-complex coordinating of 1 at the ortho-dihydroxyl
groups of the B-ring.5c 1-Carboxylate may also coordi-
nate to the Al3+. 1-OH and the 5-ester residue may be
essential to the co-pigment effect by constructing hydro-
gen bond network. The hydrophobic interaction be-
tween the aromatic acyl residue at the 5-position of
the co-pigment and the nucleus of 1 may also stabilize
the complex. This newly elucidated metal complex-
anthocyanin with non-flavonoid co-pigment exists in
the vacuoles of hydrangea sepals developing a beautiful
blue color. Further investigations are in progress.
1
23%); H NMR (CD3OD, 600 MHz) d 1.98 (dd, J = 11.0,
14.0 Hz, 1H), 2.14 (m, 1H), 2.16 (m, 1H), 2.28 (dd, J = 3.0,
15.0 Hz, 1H), 3.81 (dd, J = 3.0, 9.0 Hz, 1H), 4.22 (ddd,
J = 4.0, 9.0, 11.0 Hz, 1H), 5.44 (q, J = 3.0 Hz, 1H), 6.47
(d, J = 16.0 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H), 7.18
(d, J = 8.0 Hz, 1H), 7.24 (s, 1H), 7.69 (d, J = 16.0, 1H).
12. Compound 2 was synthesized by Sefkow et al. using the
similar synthetic route Sefkow, M.; Kelling, A.; Schilde,
U. Eur. J. Org. Chem. 2001, 14, 2735–2742.
13. During the deprotection reaction in aqueous acidic solu-
tion 5-O-acyl moiety was hydrolyzed simultaneously,
therefore the reaction was low yield.
14. Hydrogenation of 2 with H2/Pd–C gave 10 in quantitative
yield.
Acknowledgments
We are grateful to Dr. K. Oyama, Nagoya University
for valuable discussion, and Mr. S. Okumura, Okumura
Seika-En for providing plant materials. This work was
financially supported by the Ministry of Education, Sci-
ence, Sports, Culture, Technology, Japan (The 21st Cen-
tury COE Program No. 14COEB01-00, Creative
Scientific Research No. 16GS0206), Ministry of Agricul-
ture, Forestry and Fisheries of Japan (The Pioneer
Research Project), Hayashi Memorial Foundation for
Female Natural Scientists, and Yamada Science
Foundation.
15. 5-OH in 6 was selectively silylated with TBDMS-Cl–
imidazole/DMF, then 1-OH was methylated with NaH–
CH3I/DMF. After desilylation with TBAF (16, 32%) the
compound was acylated by treatment of cinnamoyl
chloride, then deprotected to give 11 (11%).
16. Hydrogenation of sikimate derivative (17) with H2/Pd–C
(29%) gave an undesired diastereo-isomer at 1-COOCH3
References and notes
(J1,2eq = 2.2 Hz, J1,2ax = 5.1 Hz, J1,6eq = 2.2 Hz, J1,6ax
=
1. (a) Goto, T.; Kondo, T. Angew. Chem., Int. Ed. Engl.
1991, 30, 17–33; (b) Brouillard, R. In The Flavonoids
Advances in Research Since 1986; Harborne, J. B., Ed.;
Chapman and Hall: London, 1994; pp 525–538.
6.2 Hz). Therefore, the H-1 was epimerized with NaOMe/
MeOH to give the thermodynamic product (18, 32%,
J1,2eq = 4.4 Hz, J1,2ax = 12.5 Hz, J1,6eq = 3.3 Hz, J1,6ax
=
12.5 Hz).