Chemistry Letters 2000
1015
When the key quinone compound 12a was treated with
K2CO3 in methanol, an intramolecular condensation between
the acyl and masked β-keto ester moieties was triggered by
nucleophilic attack of methanol to give only the aimed 3-
hydroxy-8-methoxy-9,10-anthraquinone-2-carboxylate 13a in
70% yield. Deprotection of the methyl ether of 13a with BBr3
gave aloesaponarin I (1) in 69% yield. The physical and spec-
troscopic data were identical with those of reported ones.3 The
butyroyl intermediate 12b was also converted to K1115A
methyl ester 14b. Since saponification of the methyl ester 14b
to K1115A failed, the nucleophile was changed to p-methoxy-
benzyl alcohol (PMB alcohol) and the PMB ester 15 was
obtained in 72% yield. Simultaneous deprotection of the
methyl ether and PMB ester of 15 was achieved by the treat-
ment with BBr3 at –78 ˚C to provide K1115A (2) in 59% yield.
Identity of the synthetic and authentic K1115A was confirmed
by NMR experiments of the mixed sample. On the other hand,
when the key intermediate 12a was treated with a strong base
such as KHMDS, a clean intramolecular Michael-type reaction
between the acyl and β-alkoxy α,β-unsaturated ester moieties
occurred to give only 1-hydroxy-8-methoxy-9,10-
anthraquinone-3-acetic acid (16) in 62% yield (eq 1).
In conclusion, we succeeded in constructing the 1,6- and
1,8-dihydroxy-9,10-anthraquinone skeletons from the common
pentaketo precursors via biomimetic routes. To our knowledge,
this is the first example of complete differentiation of bio-
mimetic pathways by the simple modification of reaction condi-
tions. Aloesaponarin I and K1115A were prepared in good
yields.
This work was partially supported by a Grant-in-Aid for
Scientific Research (No 12640521) from the Ministry of
Education, Science, Sports and Culture. We greatly thank Dr.
Masaki Goto (Tsukuba Lab., Eisai Co.) for the gift of authentic
K1115A.
References and Notes
1
R. H. Thomson, "Naturally Occurring Quinones III," Chapman and
Hall, London (1987).
2
For recent examples, see: F. Lombó, E. Künzel, L. Prado, A. F.
Braña, K. U. Bindseil, J. Frevert, D. Bearden, C. Méndez, J. A.
Salas, and J. Rohr, Angew. Chem., Int. Ed. Engl., 39, 796 (2000). E.
Künzel, B. Faust, C. Oelkers, U. Weissbach, D. W. Bearden, G.
Weitnauer, L. Westrich, A. Bechthold, and J. Rohr, J. Am. Chem.
Soc., 121, 11058 (1999). T. L. Graybill, E. G. Casillas, K. Pal, and C.
A. Townsend, J. Am. Chem. Soc., 121, 7731 (1999). C. M. H.
Watanabe and C. A. Townsend, J. Am. Chem. Soc., 120, 6231
(1998). P. J. Kramer, R. J. X. Zawada, R. McDaniel, C. R.
Huchinson, D. A. Hopwood, and C. Khosla, J. Am. Chem. Soc., 119,
635 (1997).
3
4
A. Yagi, K. Makino, and I. Nishioka, Chem. Pharm. Bull., 22, 1159
(1974).
H. Inouye and E. Leistner, “The Chemistry of Quinonoid
Compounds,” ed. by S. Patai and Z. Rappoport, John Wiley and
Sons, London (1988), Vol. 2, Chap. 22, p 1293.
The similar transformation to 1,6- and 1,8-dihydroxy-
anthraquinones was also achieved by employing the TBS ether
8a as a substrate. Treatment of 8a with K2CO3 in MeOH and
with KHMDS in THF brought about the similar ring closures
followed by air oxidation to give the quinone 13a and 16 in
55% and 56% yields, respectively. Very facile ring closures
observed in the reactions of 8 and 12 would be understood by
the spatial proximity between the two intramolecular reacting
carbons. From the X-ray analysis of 8a (Figure 1),12 intramole-
cular hydrogen bonding of the phenolic hydrogen is not
observed with the acetyl oxygen but with the peri-positional
oxygen, and the aromatic ring and the acetyl group are not co-
planar (52.4˚) probably due to the sterical congestion of the
substituents. Both distances of C1'–C3" and C2'–C2" are quite
short (3.97 and 3.27 Å, respectively). This conformation would
be kept in solution, because the phenolic proton signal of 8a
was observed 4.22-ppm higher than that of 2-acetyl-4,8-
dimethoxy-1-naphthol,8 where intramolecular hydrogen bond-
ing with the acetyl group would be expected (9.60 ppm for 8a
and 13.82 ppm for the latter).
5
6
R. H. Thomson, “Naturally Occurring Quinones: Recent Advances,”
4th ed., Blackie Academic & Professional, London (1997).
K. Krohn, N. Böker, U. Flörke, and C. Freund, J. Org. Chem., 62,
2350 (1997). M. Yamaguchi, T. Okuma, A. Horiguchi, C. Ikeura,
and T. Minami, J. Org. Chem., 57, 1647 (1992). T. M. Harris, C. M.
Harris, T. A. Oster, L. E. Brown, Jr., and J. Y. C. Lee, J. Am. Chem.
Soc., 110, 6180 (1988). H. Uno, Y. Naruta, and K. Maruyama,
Tetrahedron, 40, 4725, (1984). S. Mahalingam, P. C. Kuzuma, J. Y.
-C. Lee, and T. M. Harris, J. Am. Chem. Soc., 107, 7760 (1985). T.
M. Harris, A. D. Webb, and C. M. Harris, J. Am. Chem. Soc., 98,
6065 (1976).
N. Naruse, M. Goto, Y. Watanabe, T. Terasawa, and K. Dobashi, J.
Antibiot., 51, 545 (1998).
H. Uno, J. Org. Chem., 51, 350 (1986).
B. L. Pagenkopf, J. Krüger, A. Stojanovic, and E. M. Carreira,
Angew. Chem., Int. Ed. Engl., 37, 3124 (1998). Y. Kim, R. A.
Singer, and E. M. Carreira, Angew. Chem., Int. Ed. Engl., 37, 1261
(1998). R. A. Singer and E. M. Carreira, J. Am. Chem. Soc., 117,
12360 (1995).
7
8
9
10 1H NMR Data for 7a: δ (CDCl3) 0.22 (9H, s), 1.39 (3H, s), 1.59
(3H, s), 1.91 (1H, dd, J = 13.9 and 12.0 Hz), 2.25 (1H, dd, J = 13.9
and 5.6 Hz), 2.34 (3H, s), 3.93 (4H, m), 4.12 (1H, s), 7.20 (1H, br
d, J = 8.3 Hz), 7.42 (1H, br d, J = 7.3 Hz), and 7.51 (1H, dd, J =
8.3 and 7.3 Hz).
11 K. Krohn, N. Böker, A. Gauhier, G. Schäfer, and F. Werner, J.
Prakt. Chem., 338, 349 (1996).
12 Crystallographic summary for 8a: C26H34O7Si, FW = 486.64, yellow
crystal, 0.5 × 0.1 × 0.1 mm, orthorhonbic, P212121 (#19), Z = 4, a =
13.131(1) Å, b = 26.173(2) Å, c = 7.621(1) Å, V = 2619.2(5) Å3,
ρcalc = 1.23 g·cm–3, Cu Kα, F(000) = 1040.0, 2375 unique reflec-
tions. The final R = 0.075, Rw = 0.126, R1 = 0.049 (1974 reflns),
goodness-of-fit = 1.36 for 309 parameters refined on F2. The
absolute conformation was determined by the anomarous dispersion
method and the probability was over 99.5% by the Hamilton limita-
tion based on the R-factor ratio.13
13 "International Tables for X-Ray Crystallography," Kluwer Academic
Publishers, Dordrecht (1989), Vol. 4, p. 288.