Concise enantioselective syntheses of quinolactacins A and B through alternative winterfeldt oxidation

Article abstract of DOI:10.1021/jo020746a

Enantioselective total syntheses of (+)-quinolactacin B and (+)-quinolactacin A2 through asymmetric Pictet-Spengler cyclization and KO₂ oxidation-an alternative Winterfeldt condition-are described.

Full text of DOI:10.1021/jo020746a

Con cise En a n tioselective Syn th eses of
Qu in ola cta cin s A a n d B th r ou gh
Alter n a tive Win ter feld t Oxid a tion
Xuqing Zhang,* Weiqin J iang, and Zhihua Sui
Drug Discovery, J ohnson & J ohnson Pharmaceutical
Research & Development, L. L. C., 1000 Route 202, Box 300,
Raritan, New J ersey 08869
F IGURE 1. Structures of quinolacatacins A-C.
xzhang5@prdus.jnj.com
Received December 17, 2002
Abstr a ct: Enantioselective total syntheses of (+)-quinolac-
tacin B and (+)-quinolactacin A2 through asymmetric Pic-
tet-Spengler cyclization and KO2 oxidationsan alternative
Winterfeldt conditionsare described.
Novel quinolone antibiotics, quinolactacins A-C (Fig-
ure 1) were first discovered from the cultured broth of
Penicillium sp. EPF-6, which was isolated from the larvae
of the mulberry pyralid (Margaronia pyloalis Welker).1
Quinolactacin A shows inhibitory activity against tumor
necrosis factor (TNF) production by murine macrophages
and macrophage-like J 774.1 cells stimulated with li-
popolysaccharide (LPS). More recently, the two quino-
lactacin A diastereomers were isolated from solid-state
fermentation of Penicillium citrinum 90648 and named
quinolactacin A1 and quinolactacin A2 (Figure 2).2 The
relative configuration of quinolactacin A2 is assumed to
be the same as that of the originally assigned quinolac-
tacin A from the cultured broth of Penicillium sp. EPF-6
on the basis of spectroscopic analysis. Quinolactacin A1
is the C-1′ diastereomer of A2. It is interesting that
quinolactacin A2 showed 14 times higher anti-acetylcho-
linesterease activity than its diastereomer quinolactacin
A1. The quinolactacins are the first pyrrolo[3,4-b]quino-
line-type compounds isolated from microbial metabolites.
The structures are unique in that a quinolone skeleton
is conjugated with a γ-lactam ring. A biomimetic total
synthesis of quinolactacin B has been reported by Tat-
suta’s group.3 The synthesis suggests that quinolactacins
might be biologically synthesized from three components,
amino acids, anthranilic acid, and acetic acid. This
synthesis also provides a general route to the analogues
of quinolactacin-type antibiotics.
F IGURE 2. Diastereomeric quinolacatacins A1 and A2.
quinolone skeletons might be assembled by the applica-
tion of an alternative Winterfeldt oxidation of â-carbo-
lines as recently developed in our group.4 In this paper,
we describe an efficient enantioselective syntheses of
quinolactacin B and quinolactacins A1 and A2.
A retrosynthetic analysis that outlines the implemen-
tation of our synthetic protocol is shown in Scheme 1.
Thus, it was envisioned that quinolone 1 possessing the
necessary functionalities could be furnished from â-car-
boline precursor 2 by KO2 oxidation. The construction of
â-carboline 2 could be achieved by diastereoselective
Pictet-Spengler cyclization of the indole 3. It should be
noted that various indoles 3 could be prepared by
condensation of commercially available tryptamine with
the corresponding aldehydes (RCHO). This methodology
should have potential in the synthesis of a series of
quinolactacin analogues.
We first investigated the diastereoselective syntheses
of chiral â-carboline-type structures 5 (Scheme 2). Asym-
metric Pictet-Spengler reactions on the precursors 4 by
employing chiral methyl benzyl or chiral naphthylethyl
groups as chiral auxiliaries have been reported in the
literature.5 However, these methods when employed on
our substrates resulted in very low diastereoselectivities
of the cyclization adducts. We were then attracted by
Waldmann’s asymmetric Pictet-Spengler cyclization
methodology using N,N-phthaloyl-protected amino acid
chlorides as chiral auxiliaries.6 Thus, the synthetic route
to (+)-quinolactacin B is shown in Scheme 3. Compound
8a was prepared according to Waldmann’s protocol using
These unique structures elicited our interest in the
quinolactacin alkaloids as targets for total synthesis. We
envisioned that the total synthesis of quinolactacin B
would confirm its absolute configuration as assigned by
the literature.1b,2 More importantly, the first total syn-
thesis of quinolactacin A will establish both absolute
configurations of A1 and A2, which have not been clearly
determined. In view of synthetic strategy, the functional
(4) (a) J iang, W.; Zhang, X.; Sui, Z. Org. Lett. 2003, 5, 43. (b) Zhang,
X.; J iang, W.; Sui, Z. Asymmetric total syntheses of quinolactacin A
and B through an improved Winterfeldt Oxidation. Abstracts of Papers;
224th ACS National Meeting, Boston, MA, 18-22 Aug, 2002; American
Chemical Society: Washington, DC, 2002.
(5) (a) Kawate, T.; Yamanaka, M.; Nakagawa, M. Heterocycles 1999,
50, 1033. (b) Soe, T.; Kawate, T.; Fukui, N.; Hino, T.; Nakagawa, M.
Heterocycles 1996, 42, 347. (c) Gremmen, C.; Willemse, B.; Wanner,
M.; Koomen, G.-J . Org. Lett. 2000, 2, 1955. (d) J iang, W.; Sui, Z.; Chen,
X. Tetrahedron Lett. 2002, 43, 8941.
* To whom correspondence should be addressed. Fax: 908-526-6469.
(1) (a) Kakinuma, N.; Iwai, H.; Takahashi, S.; Hmano, K.; Yanag-
isawa, T.; Nagai, K.; Tanaka, K.; Suzuki, K.; Kirikae, F.; Kirikae, T.,
Nakagawa, A. J . Antibiot. 2000, 53, 1247. (b) Takahashi, S.; Kakinuma,
N.; Iwai, H.; Yanagisawa, T.; Nagai, K.; Suzuki, K.; Tokunaga, T.,
Nakagawa, A. J . Antibiot. 2000, 53, 1252.
(2) Kim, W.-G.; Song, N.-K.; Yoo, I.-D. J . Antibiot. 2001, 54, 831.
(3) Tatsuta, K.; Misawa, H.; Chikauchi, K. J . Antibiot. 2001, 54,
109.
(6) (a) Waldmann, H.; Schmidt, G.; Henke, H.; Burkard, M. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2402. (b) Schmidt, G.; Waldmann, H.;
Henke, H.; Burkard, M. Chem. Eur. J . 1996, 2, 1565.
10.1021/jo020746a CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/26/2003
J . Org. Chem. 2003, 68, 4523-4526
4523

according to the studies by Waldmann.6 The chiral
auxiliary of the Pictet-Spengler adduct 8a could be
readily removed by cleavage of the amide bond of 8a with
LiAlH4 to give the enantiomerically pure tetrahydro-â-
carboline 9 in 78% yield. Protection of the sec-amine
group of 9 with Boc2O and Et3N (95% yield),8 followed
by modified Winterfeldt oxidation (KO2, 18-C-6) of the
resulting protected indole 10 gave the quinolone 11 in
75% yield. This is consistent with our previous findings
that KO2 is an efficient and mild reagent for transforma-
tion of â-carbolines to pyrroloquinolones.4 Traditional
Winterfeldt oxidation conditions using a strong base9,10
such as t-BuOK or NaH were avoided in our synthesis
due to the possibility of epimerization in the course of
the rearrangement. It is known that the oxidation of
â-carbolines under Winterfeldt conditions results in a
ketone amide intermediate, which could be very sensitive
to base-induced epimerization.11 To evaluate the mildness
of KO2 and 18-C-6 combination, we determined the ee
value of 11 by chiral HPLC. After integration of the peak
of chiral 11 on HPLC using rac-1112 as the standard, the
ee of chiral 11 was determined as >95%. This result
demonstrated that there was no epimerization in the
process of the rearrangement by using KO2 condition. The
quinolone 11 was then methylated with MeI in the
presence of K2CO3 to afford the methylated quinolone 12a
and the methylated pyridine 12b in 6:1 ratio (88% yield).
The isomers 12a and 12b were easily separated by
column chromatography. The desired quinolone 12a was
then subjected to the allylic oxidation conditions to
SCHEME 1. Retr osyn th etic An a lysis of
Qu in ola cta cin s A a n d B
SCHEME 2. Asym m etr ic P ictet-Sp en gler
Cycliza tion
N,N-phthaloyl-protected amino acid chloride 6a derived
from L-(+)-tert-leucine7 as chiral auxiliary in 68% yield
from tryptamine (7)and ∼7:1 ratiotoits C-3 diastereomer.6b
Because L-(+)-tert-leucine-derived chiral auxiliary was
used for the formation of the intermediate acyl iminium
species, the absolute stereochemistry of C-3 in the
â-carboline 8a was assigned as the R configuration
SCHEME 3. Asym m etr ic Tota l Syn th esis of (+)-Qu in ola cta cin B
4524 J . Org. Chem., Vol. 68, No. 11, 2003

SCHEME 4. Asym m etr ic Tota l Syn th esis of Qu in ola cta cin A2
deliver the ketone lactam functionality in the target
molecule. Several attempts to oxidize 12a to 13 with
common oxidants such as SeO2, MnO2, and RuO2 were
unsuccessful. However, treatment of 12a with PDC (0.2
equiv) and t-BuOOH (2.0 equiv) in PhH resulted in the
desired ketone lactam 13 in 25% yield.13 We then
optimized the reaction using CuBr as the catalyst to
improve the yield to 65%.14 After deprotection of Boc
group from 13 by the treatment with TFA in CH2Cl2, (+)-
(separated by column chromatography), allylic oxidation
of the desired quinolone 18a to 19 and deprotection of
Boc group of 19 (structure not shown), (+)-quinolactacin
A2 was obtained as a single enantiomer [[R]20 +19.5 (c
D
0.4, DMSO) [lit.1b [R]25 +17.9 (c 0.13, DMSO)]]. Spec-
D
troscopic data for synthetic (+)-quinolactacin A2 are in
full accordance with the data as reported in the litera-
ture.1b,2 Both C-3 and C-1′ stereochemistry are estab-
lished as the S configuration.
quinolactacin B was obtained in 85% yield [[R]20 +5.8
Quinolactacin A1 has been assigned as the diastere-
omer of A2 on the basis of its spectral data. Although
quinolactacin A1 was isolated concurrently with A2 from
the same microbial metabolites, it is still not clear
whether they are real diastereomers at C-1′. Due to the
unavailability of optically pure (R)-(-)-2-methylbutanal,
we took advantage of commercially available rac-2-
methylbutanal as starting material. Following the syn-
thetic route described, a pair of C-1′ diastereomers were
obtained. Chiral HPLC was used for separation of these
two diastereomers (see the Experimental Section). The
column was eluted with 2-propanol at a flow rate of 1
mL/min to afford quinolactacin A2 with a retention time
of 4.276 min and its C-1′ diastereomer at 5.706 min. From
1H NMR of the diastereomeric mixture, the C-1′ diaste-
D
(c 0.2, DMSO) [lit.1b [R]25 -3.3 (c 0.15, DMSO)]]. Our
D
synthetic quinolactacin B showed spectral data identical
with that of the natural product reported. The optical
rotation of our synthetic product is the opposite of the
natural product, which demonstrates that our product
is the enantiomer of the natural product. Thus, the result
confirmed that the absolute stereochemistry of C-3 in
natural (-)-quinolactacin B is the S configuration, as
assigned by the biomimetic synthesis.3 Utilizing the same
route, the natural product can be synthesized by using
the D-amino acid derived chiral auxiliary.
Due to the indetermination of absolute stereochemistry
of quinolactacin A, we extended the above synthetic route
to the synthesis of quinolactacin A. We assumed that C-1′
stereochemistry of quinolactacin A2 (reported first in ref
1b as quinolactacin A) could be derived from a natural
amino acid. Thus, (S)-(+)-2-methylbutanal15 was used as
the aldehyde component for the synthesis. The detailed
synthetic route to (+)-quinolactacin A2 is shown in
Scheme 4. Coupling tryptamine (7) with (S)-(+)-2-meth-
ylbutanal gave the Schiff base 3b (structure not shown
in Scheme 4). Asymmetric Pictet-Splengler cyclization
of 3b using the more expensive D-amino acid derived
chiral auxiliary 6b in the presence of Ti(O-n-Pr)4 afforded
the â-carboline 14a and 14b in 4:1 ratio. Thus, asym-
metric induction by the D-chiral auxiliary resulted in the
S configuration at C-3 of the major diastereomer 14a .
Removal of the chiral auxiliary from 14a by LAH
provided the chiral â-carboline 15 (structure not shown).
Reprotection of the corresponding sec-amine with Boc2O
(16), followed by KO2 oxidation, gave the quinolone 17
in 61% yield. After methylation of 17 to 18a and 18b
(7) For preparation of the chiral auxiliary, see: Sheehan, J .;
Chapman, D.; Roth, R. J . Am. Chem. Soc. 1952, 74, 3822.
(8) Lounasmaa, M.; Karvinen, E.; Koskinen, A.; J okela, R. Tetra-
hedron 1987, 43, 2135.
(9) Winterfeldt, E. Liebigs Ann. Chem. 1971, 745, 23.
(10) (a) Warneke, J .; Winterfeldt, E. Chem. Ber. 1972, 105, 2120.
(b) Boch, M.; Korth, T.; Nelke, J . M.; Pike, D.; Radunz, H.; Winterfeldt,
E. Chem. Ber. 1972, 105, 2126.
(11) (a) Demerson, C. A.; Humber, L. G. Can. J . Chem. 1979, 57,
3296. (b) Carniaux, J .-F.; Han-Fan, C.; Royer, J .; Husson, H.-P. Synlett
1999, 5, 563.
(12) rac-11 was prepared from rac-9, available from acid-catalyzed
Pictet-Spengler cyclization of tryptamine and isobutyraldehyde.
(13) Schultz, A. G.; Taveras, A. G.; Harrington, R. E. Tetrahedron
Lett. 1988, 29, 3907.
(14) Salvador, J . A. R.; Sa´ e Melo, M. L.; Campos Neves, A. S.
Tetrahedron Lett. 1997, 38, 119.
(15) For preparation of (S)-(+)-methylbutanal, see: J auch, J .; Czesla,
H.; Schurig, V. Tetrahedron 1999, 55, 9787.
(16) Gremmen, C.; Willemse, B.; Wanner, M.; Koomen, G. J . Org.
Lett. 2000, 2, 1955.
(17) Kawate, T.; Nakagawa, M.; Yamazaki, H.; Hirayama, M.; Hino,
T. Chem. Pharm. Bull. 1993, 41, 287.
J . Org. Chem, Vol. 68, No. 11, 2003 4525

9H), 1.21 (d, J ) 6.9 Hz, 3H), 0.78 (d, J ) 6.9 Hz, 3H); 13C NMR
(CDCl3) δ 173.7, 155.9, 152.4, 142.1, 132.2, 127.2, 126.7, 123.9,
117.6, 115.6, 80.6, 67.5, 51.6, 36.7, 34.5, 28.8, 21.4, 16.2, 14.5;
IR (neat, cm-1) 1697, 1625; MS (m/z) 343 [M + H]+, 365 [M +
Na]+; HRMS calcd for C20H26N2O3 (MH+) 343.2022, found
343.2033. Anal. Calcd for C20H26N2O3: C, 70.15; H, 7.65; N, 8.18.
Found: C, 70.02; H, 7.71; N, 8.08. 12b: 1H NMR (CDCl3) δ 8.21
(d, J ) 7.5 Hz, 1H), 8.03 (d, J ) 7.4 Hz, 1H), 7.68 (t, J ) 6.8 Hz,
1H), 7.45 (t, J ) 6.8 Hz, 1H), 5.38 (d, J ) 10.5 Hz, 1H), 5.01 (s,
1H), 4.90 (d, J ) 10.5 Hz, 1H), 4.22 (s, 3H), 2.42 (m, 1H), 1.55
(s, 9H), 0.98 (d, J ) 6.9 Hz, 6H); IR (neat, cm-1) 1692; MS (m/z)
343 [M + H]+, 365 [M + Na]+, 707 [2M + Na]+.
reomer of quinolactacin A2 could be differentiated by
comparison of the spectrum of A2. The spectrum is in
agreement with the data of quinolactacin A1 reported in
ref 2. This result confirms quinolactacin A1 is the C-1′
diastereomer of A2.
In conclusion, we have achieved the enantioselective
total syntheses of (+)-quinolactacin B and (+)-quinolac-
tacin A2. The route described herein affords (+)-quino-
lactacin B in overall 16% yield over eight steps from
tryptamine and (+)-quinolactacin A2 in 8% yield. The
synthetic protocol is highlighted by asymmetric Pictet-
Spengler cyclization and KO2 oxidation reactions. We also
confirmed that quinolactacin A1 is the C-1′ diastereomer
of A2. The present synthesis should be amenable to
provide general access to members of the quinolactacin
family and analogues.
3-(R)-Isop r op yl-4-m eth yl-1,9-d ioxo-1,3,4,9-tetr a h yd r op y-
r r olo[3,4-b]q u in olin e-2-ca r b oxylic Acid ter t-Bu t yl E st er
(13). To a solution of 12a (90 mg, 0.26 mmol) and CuBr (8 mg,
0.06 mmol) in PhH (6 mL) was added t-BuOOH (5.0 M in decane,
106 µL, 0.52 mmol) at room temperature. The mixture was then
heated at 50 °C for 2 h and stirred at room temperature
overnight. The solid was filtered through a pad of Celite. The
filtrate was then concentrated to give a light green oil, which
contained the crude product. Flash column chromatography
(silica gel, EtOAc, then CH2Cl2/MeOH ) 10:1) afforded 13 as a
white solid (61 mg, 65%): mp 254-255 °C dec; [R]20D +75 (c 0.26,
MeOH); 1H NMR (DMSO-d6) δ 8.46 (d, J ) 7.9 Hz, 1H), 7.81 (t,
J ) 7.8 Hz, 1H), 7.66 (d, J ) 8.5 Hz, 1H), 7.52 (t, J ) 7.5 Hz,
1H), 5.34 (d, J ) 2.0 Hz, 1H), 3.89 (s, 3H), 2.43 (m, 1H), 1.58 (s,
9H), 1.24 (d, J ) 6.8 Hz, 3H), 0.73 (d, J ) 6.8 Hz, 3H); 13C NMR
(DMSO-d6) δ 173.5, 164.8, 163.1, 150.8, 141.0, 134.2, 126.5,
125.5, 124.2, 121.5, 114.8, 108.5, 79.5, 62.0, 34.9, 28.0, 27.6, 20.6,
14.5; IR (neat, cm-1) 1753, 1625, 1605; MS (m/z) 357 [M + H]+,
379 [M + Na]+, 735 [2M + Na]+; HRMS calcd for C20H24N2O4
(MH+) 357.2178, found 357.2171.
Exp er im en ta l Section
1
Gen er a l Meth od s. All melting points were uncorrected. H
NMR spectra were obtained at 400 MHz and 13C NMR spectra
were recorded at 100 MHz, with d-chloroform or DMSO-d6 as
solvent. Chemical shifts are reported in ppm downfield from
TMS as an internal standard. Elemental analyses were per-
formed by Quantitative Technologies Inc., Whitehouse, NJ . Thin-
layer chromatography was carried out using silica gel 60 (250
µM layer) plates with UV detection. Flash chromatography was
done using EM science silica gel 60 (230-400 mesh). N,N-
Phthaloyl-protected amino acid chlorides 6a and 6b were
prepared according to the method reported by Sheeman.7
3-(R)-Isop r op yl-9-oxo-1,3,4,9-t et r a h yd r op yr r olo[3,4-b]-
qu in olin e-2-ca r boxylic Acid ter t-Bu tyl Ester (11). To a
solution of 10 (105 mg, 0.334 mmol) and 18-crown-6 (88 mg,
0.334 mmol) in DMF (3 mL) was added KO2 (95 mg, 1.34 mmol)
[Caution! Explosive Material!] in one portion at room temper-
ature. The reaction solution turned red. After 30 min, the red
color disappeared and the reaction was stirred for another 2 h.
The extra KO2 was then quenched with saturated NH4Cl, and
EtOAc was added into the reaction. The aqueous phase was
extracted five times with EtOAc. The combined organic layer
was washed with brine, dried over anhydrous Na2SO4, filtered,
and concentrated to give the crude product. Flash column
chromatography (silca gel, EtOAc) afforded 11 as a white solid
(83 mg, 75%). The ee value is >95% on the basis of Chiral AD
(+)-Qu in ola cta cin B. To a solution of 13 (50 mg, 0.14 mmol)
in CH2Cl2 (2 mL) was added TFA (0.5 mL) at room temperature.
The reaction mixture was stirred for 2 h. Saturated NaHCO3
was added, and the aqueous layer was extracted three times
with CH2Cl2. The combined organic layer was washed with brine,
dried over anhydrous Na2SO4, filtered, and concentrated to give
(+)-quinolactacin B as a white solid (31 mg, 85%). The product
was pure enough for characterization without further purifica-
1
tion. The H NMR and 13C NMR match the data reported in ref
1b: [R]20D +5.8 (c 0.12, DMSO) [lit.1b (-)-quinolactacin B, [R]25
-3.3 (DMSO)].
D
(+)-Qu in ola cta cin A2: white solid; yield 85%; [R]20 +19.5
HPLC-MS analysis: mp 245-247 °C dec; [R]20 +191 (c 0.21,
D
D
1
(c 0.7, DMSO) [lit.1b [R]25 +17.9 (c 0.13, DMSO)]. The H NMR
MeOH); 1H NMR (DMSO-d6) δ 8.16 (d, 1H, J ) 7.5 Hz), 7.62
(m, 2H), 7.30 (d, 1H, J ) 6.8 Hz), 5.05 (d, 1H, J ) 13.5 Hz), 4.55
(d, 1H, J ) 7.0 Hz), 4.21 (m, J ) 13.5 Hz, 1H), 2.32 (m, 1H),
1.46 (s, 9H), 1.02 (d, 3H, J ) 7.5 Hz), 0.82 (d, 3H, J ) 2.0 Hz);
13C NMR (CDCl3 + DMSO-d6) δ 174.1, 154.6, 140.8, 131.6, 125.4,
125.0, 123.3, 119.0, 116.0, 115.5, 82.2, 66.9, 34.5, 33.2, 28.4, 19.7,
17.0, 11.5; IR (neat, cm-1) 3395, 1684, 1620; MS (m/z) 329 [M +
H]+, 679 [2M + Na]+; HRMS calcd for C19H24N2O3 (MH+)
329.1865, found 329.1869. Anal. Calcd for C19H24N2O3: C, 69.49;
H, 7.37. Found: C, 69.25; H, 7.34.
D
and 13C NMR match the data reported in ref 1b.
Sep a r a tion of Qu in ola cta cin A1 a n d A2 by An a lytica l
Ch ir a l AD HP LC-MS. Diastereomeric quinolactacins A1 and
A2 were prepared using the same synthetic route described in
Scheme 4 from rac-2-methylbutanal. From 1H NMR of the
diasteromeric mixture (A1 and A2), spectra data of A1, compared
with that of A2, matched the data in ref 2. HPLC-MS (Chiral-
pak AD column, 250 mm × 46 mm) was used for separation of
the two diastereomers. The elution with 2-propanol at a flow
rate of 1.0 mL/min on the column afforded A2 (peak 1) with a
retention time at 4.276 min and A1 (peak 2) at 5.706 min.
Quinolactacin A2 prepared from (S)-(+)- 2-methylbutanal was
used for comparison.
3-(R)-Isopr opyl-4-m eth yl-9-oxo-1,3,4,9-tetr ah ydr opyr r olo-
[3,4-b]qu in olin e-2-ca r boxylic Acid ter t-Bu tyl Ester (12a )
a n d 3-(R)-Isop r op yl-9-m eth oxy-1,3-d ih yd r op yr r olo[3,4-b]-
qu in olin e-2-ca r boxylic Acid ter t-Bu tyl Ester (12b). To a
solution of 11 (110 mg, 0.33 mmol) and K2CO3 (92 mg, 0.67
mmol) in DMF (5 mL) was added MeI (42 µL, 0.67 mmol) at
room temperature. After 2 h, the mixture was diluted with
EtOAc and water. The aqueous phase with extracted twice with
EtOAc. The combined organic layer was washed with brine,
dried over anhydrous Na2SO4, filtered, and concentrated to give
the crude product. Flash column chromatography (silica gel,
hexanes/EtOAc ) 3:1, then 1:1) afforded 12b as a yellow oil (15
mg, 13%) and 12a as a white solid (86 mg, 75%). 12a : mp 219-
Ack n ow led gm en t. We are grateful to Dr. Naresh
J ain for help with the HPLC separation and Dr.
Raymond Ng for help with manuscript preparation.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
1
tails and characterizations for all new compounds; H NMR
and 13C NMR spectra of all new compounds; 1H NMR spectra
of (+)-quinolactacin A2 and (+)-quinolactacin B. This material
is available free of charge via the Internet at http://pubs.acs.org.
221 °C; [R]20 +168 (c 0.19, MeOH); 1H NMR (CDCl3) δ 8.52 (d,
D
J ) 7.5 Hz, 1H), 7.73 (t, J ) 7.6 Hz, 1H), 7.48 (d, ) 8.2 Hz, 1H),
7.42 (t, J ) 7.9 Hz, 1H), 5.41 (s, 1H), 4.88 (d, J ) 12.5 Hz, 1H),
4.42 (d, J ) 12.5 Hz, 1H), 3.78 (s, 3H), 2.25 (m, 1H), 1.51 (s,
J O020746A
4526 J . Org. Chem., Vol. 68, No. 11, 2003