Total synthesis of secobatzelline B

Article abstract of DOI:10.1080/00397910701410954

A concise and efficient total synthesis of Secobatzelline B is reported. The synthesis involves eight steps starting from known 4,6,7-trimethoxyindole. Synthetic tactics involve a one-step reduction of an indole-3-glyoxalic ester using LiAlH4, resulting i

Full text of DOI:10.1080/00397910701410954

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Total Synthesis of Secobatzelline B
Bidhan A. Shinkre a & Sadanandan E. Velu a
a Department of Chemistry, University of Alabama at Birmingham,
Birmingham, Alabama, USA
Published online: 11 Jul 2007.
To cite this article: Bidhan A. Shinkre & Sadanandan E. Velu (2007) Total Synthesis of Secobatzelline B,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:14, 2399-2409, DOI: 10.1080/00397910701410954
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Synthetic Communicationsw, 37: 2399–2409, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701410954
Total Synthesis of Secobatzelline B
Bidhan A. Shinkre and Sadanandan E. Velu
Department of Chemistry, University of Alabama at Birmingham,
Birmingham, Alabama, USA
Abstract: A concise and efficient total synthesis of Secobatzelline B is reported. The
synthesis involves eight steps starting from known 4,6,7-trimethoxyindole. Synthetic
tactics involve a one-step reduction of an indole-3-glyoxalic ester using LiAlH4,
resulting in complete reduction of the ester group and a partial reduction of the viny-
logous amide carbonyl group. Synthesis also involves the use of a mixture of NaCl and
oxone as a new reagent for regioselective chlorination of an indoloquinone derivative.
Keywords: indoloquinone, total synthesis, secobatzelline
INTRODUCTION
For the past quarter of a century, global marine sources have proven to be rich
sources of vast array of new medicinally valuable compounds.[1] These natural
products exist as secondary metabolites in marine invertebrates such as
sponges, bryazoa, tunicates, and ascidians. Most of these alkaloids are
isolated from marine sponges. More than 15,000 marine products have been
described thus far. Sponges, in particular, are responsible for more than
5300 different products, and every year hundreds of new compounds are
being discovered.[2,3] Many of these compounds have generated interest as
challenging problems for structure elucidation and synthesis, as well as for
their biological activities. Most bioactive compounds from sponges have
exhibited anti-inflammatory, antitumor, immunosuppressive, neurosuppres-
sive, antiviral, antimalarial, and antibiotic activities. Over the past decade,
Received in the USA December 8, 2006
Address correspondence to Sadanandan E. Velu, Department of Chemistry, Univer-
sity of Alabama at Birmingham, 901 14th Street South, Birmingham, AL 35294-1240,
USA. E-mail: svelu@uab.edu
2399

2400
B. A. Shinkre and S. E. Velu
several new natural products and related compounds derived from marine
sources have entered advanced preclinical and clinical trials.[4] Marine
alkaloids are isolated in only very small quantities, precluding their
thorough biological evaluations. Laboratory synthesis of these compounds
or their analogs in larger quantities will allow us to perform a more
complete study of their biological profiles.
Marine sponges of the genera Latrunculia, Batzella, Prianos, and Zyzzya
are rich sources of alkaloids bearing a pyrrolo[4,3,2-de]quinoline skeleton.[5,6]
This series of alkaloids comprises about 60 metabolites including discorhab-
dins,[7] epinardins,[8] batzellines,[9] isobatzellines,[9] makaluvamines,[10–14]
damirones,[11–15] and veiutamine.[16] Pyrrolo[4,3,2-de]quinoline alkaloids
have shown a variety of biological activities such as inhibition of topoisome-
rase I[14] and II,[10] cytotoxicity against different tumor cell lines,[10,17] and
antifungal[14] and antimicrobial activities.[18] This class of alkaloids has
recently received increasing attention as a source of new anticancer
drugs.[19–24] Their unique fused-ring skeletons carrying interesting biological
properties have made them challenging targets for several synthetic and bio-
logical studies. There has been a rapid growth of interest in the synthesis and
biological evaluation of this class of compounds and their analogs. Several
reviews have been published on the chemistry and bioactivity of this class
of compounds.[6,25,26]
Secobatzelline A(1) and B(2) (Figure 1) are two marine natural products
structurally related to pyrrolo[4,3,2-de]quinoline alkaloids and are isolated
from a deep-water marine sponge of genus Batzella.[27,28] Secobatzelline A
possesses an unusual pyrroloaminoquinone moiety, and Secobatzelline B
possesses a pyrroloquinone moiety. Secobatzellines A and B are probable pre-
cursors of pyrrolo[4,3,2-de]quinoline alkaloids.
Secobatzelline A and B have exhibited interesting biological activities.
Secobatzelline A and B inhibit the phosphatase activity of calcineurin,
which is a serine-threonine protein phosphatase involved in signal transduc-
tion and is recognized as one of the principal signaling molecules that
regulates the immune response. Secobatzelline A also inhibits the peptidase
activity of CPP32. Secobatzelline A and B also showed in vitro cytotoxicity
against P-388 and A-549 cell lines.[27,28] Even though these compounds
Figure 1. Secobatzellines and structurally related isobatzellines.

Total Synthesis of Secobatzelline B
2401
have been known since 1999, a synthesis of these compounds has not been
reported in the literature. As a part of our ongoing interest in the synthesis
of pyrroloquinone, dipyrroloquinone, and pyrroloiminoquinone alkaloids,
we report a total synthesis of secobatzelline B.
RESULTS AND DISCUSSION
Synthesis of secobatzelline B is outlined in Scheme 1. Synthesis started with
previously known 4,6,7-trimethoxyindole (5), which is prepared in four steps
starting from commercially available 2,4,5-trimethoxybenzaldehyde.[29]
Treatment of 4,6,7-trimethoxyindole with oxalyl chloride in anhydrous
ether resulted in the formation of the indole-3-glyoxalyl chloride derivative.
This product was not isolated and characterized. Instead, it was reacted with
anhydrous ethanol to form glyoxalic ester 6 in 88% overall yield.
Our next attempt was to reduce the glyoxalic ester side chain of compound
6 to the corresponding dialcohol. Reduction of compound 6 was carried out
using LiAlH4 with the anticipation that the ester group would get reduced to
a primary alcohol and the vinylogous amide carbonyl group would get
reduced to a secondary alcohol in one step. However, this reduction did not
yield the expected dialcohol. Instead, it gave a mixture of products in which
the completely reduced product, monoalcohol 7, was the major component.
Scheme 1.

2402
B. A. Shinkre and S. E. Velu
To achieve the partial reduction of the vinylogous amide carbonyl group
present in compound 6, it was deactivated by protecting the indole nitrogen
with an electron-withdrawing tosyl group. This was accomplished by
treatment of 6 with tosic anhydride in the presence of NaH in anhydrous
DMF to obtain the N-tosylated compound 8 in 84% yield. Reduction of the
N-tosylated glyoxalic ester 8 using LiAlH4 in a mixture of anhydrous ether
and THF resulted in partial reduction to provide the expected dialcohol 9 in
81% yield. Hydroxyl groups of 9 were then protected with acetyl groups by
treatment with acetic anhydride in the presence of Et3N and N,N-dimethyl-
aminopyridine (DMAP) in CH2Cl2 to yield the diacetyl derivative 10 in
96% yield. Oxidation of 10 to the corresponding quinone 11 was carried out
by treatment with ceric ammonium nitrate (CAN) in the presence of
nBu4NHSO4 in CH2Cl2 in 65% yield. Introduction of chlorine at the
5-position of quinone 11 was carried out in 45% yield by treatment with
NaCl and oxone in a mixture of EtOAc and water to afford the chlorinated
product 12. In this reaction, NaCl reacts with oxone, providing a mild
supply of the chlorine required for this reaction. The methoxy group at the
6-position of the quinone 12 was replaced by an amino-group by treatment
with NH4OH in EtOH to provide the amino-substituted compound 13 in
58% yield. Deprotection of acetyl and tosyl groups in compound 13 was
carried out in one step by treatment with NaOMe in MeOH to provide the
final product, Secobatzelline B. Spectral data of the synthetic Secobatzelline
B were in excellent agreement with the literature values.[28]
CONCLUSION
In conclusion, a concise and efficient total synthesis of Secobatzelline B
starting from known 4,6,7-trimethoxyindole is disclosed. The advantages of
this synthesis include its small number of steps, procedural simplicity, and
high efficiency. The synthetic procedures described are general and could
be used for the synthesis of other structurally similar alkaloids. The
synthesis involves eight steps. A key step of this synthesis is the one-step
reduction of a glyoxalic ester using LiAlH4, resulting in complete reduction
of the ester group and partial reduction of the vinylogous amide carbonyl
group to produce a dialcohol in one step. A new methodology for the regiose-
lective chlorination of an indole quinone derivative using a mixture of NaCl
and oxone as a mild source of Cl2 is employed in the synthesis.
EXPERIMENTAL
Melting points were determined using an Electrothermal 9100 apparatus and
are uncorrected. IR spectra were taken with Brucker Vector-22 and Bomen
MB-104 instruments. All 1H and 13C NMR spectra were recorded on a

Total Synthesis of Secobatzelline B
2403
Brucker 300-MHz spectrometer using TMS as internal standard. The values of
chemical shifts (d) are given in parts per million (ppm) and coupling constants
(J) in Hertz. Elemental analyses were performed by Atlantic Microlab,
Norcross, Georgia, and the results are within +0.4% of theoretical values.
Reactions were monitored by thin-layer chromatography (TLC) (Whatmann,
Si gel, UV 254, 25-mM plates), and flash column chromatography was done
using Baker silica gel (40 mM) in the solvent systems indicated. The solvents
used for reactions were purchased as anhydrous in Sure-SealTM bottles from
Aldrich chemical company. The chemicals used were purchased from
Aldrich, Lancaster, or Acros chemical companies and were used as received.
Ethyl 2-(4,6,7-Trimethoxyindol-3-yl)-2-oxoacetate (6)
To a solution of 4,6,7-trimethoxyindole 5 (1.0 g, 4.83 mmol) in anhydrous
ether (50 mL) at 08C, a solution of oxalyl chloride (0.63 mL, 7.24 mmol) in
anhydrous ether (10 mL) was added dropwise over a period of 15 min. The
reaction mixture was stirred and allowed to attain room temperature, at
which it was stirred for another 2 h. Ethanol (1.41 mL, 24.1 mmol) was
then added to the reaction mixture and stirred at room temperature for 2 h.
TLC examination (ethyl acetate/hexanes, 1:1) revealed that the reaction
was complete. The solvent was removed under vacuum. The residue
obtained was dissolved in dichloromethane (100 mL) and washed with
water (3 ꢀ 50 mL) and brine (1 ꢀ 50 mL). The organic layer was dried
over Na2SO4 and filtered. The solvent was removed from the filtrate under
vacuum to obtain the crude product, which was purified by column chromato-
graphy over silica gel (15 ꢀ 3 cm) using ethyl acetate/hexanes (1:1) as eluent
to afford the pure product 6 (1.3 g, 88%); oil; 1H NMR (CDCl3) d 1.38 (t, 3H,
J ¼ 7.2 Hz), 3.90 (s, 3H), 3.92 (s, 3H), 3.94 (s, 3H), 4.38 (q, 2H, J ¼ 7.2 Hz),
6.41 (s, 1H), 8.04 (d, 1H, J ¼ 3.3 Hz), and 9.14 (br s, 1H); 13C NMR (CDCl3)
d 13.9, 56.1, 57.1, 61.1, 61.7, 93.2, 110.2, 114.8, 128.8, 132.3, 134.8, 148.3,
149.6, 164.9, and 181.2; IR (CHCl3) 1636, 1732, 3290 cm21; MS (ESþ) m/z
308 (M þ H). Anal. calcd. for C15H17NO6: C, 58.63; H, 5.58; N, 4.56.
Found: C, 58.35; H, 5.56; N, 4.46.
Ethyl 2-(4,6,7-Trimethoxy-1-tosylindol-3-yl)-2-oxoacetate (8)
To a suspension of KH (0.195 g, 4.86 mmol) in anhydrous THF (25 mL) under
an N2 atmosphere, a solution of 6 (1.15 g, 3.74 mmol) in anhydrous THF
(40 mL) was added dropwise over a period of 30 min. The reaction mixture
was stirred at room temperature for 2 h. The reaction mixture was then
cooled to 08C using an ice bath, and a solution of tosic anhydride (1.586 g,
4.86 mmol) in anhydrous THF (25 mL) was added dropwise at 08C over a
period of 30 min. The ice bath was removed, and it was allowed to attain

2404
B. A. Shinkre and S. E. Velu
room temperature and stirred for 12 h at room temperature. TLC examination
(ethyl acetate/hexanes, 2:3) revealed that the reaction was complete. The
reaction mixture was then cooled back to 08C and quenched by a careful
slow addition of water (2 mL). The solvent was completely removed under
vacuum. The residue obtained was dissolved in dichloromethane (150 mL)
and washed with water (3 ꢀ 100 mL) and brine (1 ꢀ 100 mL). The organic
layer was dried over Na2SO4 and filtered, and the solvent was removed
under vacuum to obtain the crude product, which was purified by column
chromatography over silica gel (15 ꢀ 4 cm) using ethyl acetate/hexanes
(2:3) to afford the pure product 8 as a yellow solid (1.45 g, 84%); mp 125–
1
1268C; H NMR (CDCl3) d 1.39 (t, 3H, J ¼ 6.6 Hz), 2.38 (s, 3H), 3.82
(s, 3H), 3.84 (s, 3H), 3.88 (s, 3H), 4.38 (q, 2H, J ¼ 6.6 Hz), 6.43 (s, 1H),
7.28 (d, 2H, J ¼ 9.0 Hz), 7.78 (d, 2H, J ¼ 9.0 Hz), and 8.44 (s, 1H); 13C
NMR (CDCl3) d 13.9, 21.5, 55.8, 56.6, 60.7, 62.0, 94.0, 112.3, 117.0,
126.1, 127.7 (2C), 129.7 (2C), 130.4, 134.3, 135.2, 145.1, 148.6, 151.3,
163.1, and 182.2; IR (CHCl3) 1680, 1737 cm21; MS (ESþ) m/z 462
(M þ H). Anal. calcd. for C22H23NO8S: C, 57.26; H, 5.02; N, 3.04. Found:
C, 56.88; H, 4.97; N, 3.25.
1-(4,6,7-Trimethoxy-1-tosylindol-3-yl)ethane-1,2-diol (9)
To a solution of compound 8 (2.60 g, 5.64 mmol) in a mixture of anhydrous
ether (100 mL) and anhydrous THF (50 mL) at 258C, LiAlH4 (0.749 g,
19.7 mmol) was added in small portions. The reaction mixture was allowed
to warm up to 108C, then stirred at that temperature for 2 h. TLC examination
(ethyl acetate/hexanes, 3:1) indicated the completion of the reaction. The
reaction mixture was then cooled back to 08C and quenched by slow
addition of an aqueous solution of saturated Na2SO4. The inorganic solids
were filtered off, and the residue was washed with dichloromethane
(75 mL). The combined filtrate was concentrated under vacuum to obtain
the crude residue. The crude residue was dissolved in dichloromethane
(100 mL) and washed with water (3 ꢀ 50 mL) and brine (1 ꢀ 50 mL). The
organic layer was dried over Na2SO4 and filtered, and the solvent was
removed under vacuum to obtain the crude product, which was purified by
column chromatography over silica gel (15 ꢀ 3 cm) using ethyl acetate/
hexanes (3:1) to afford the pure product 9 as a white solid (1.92 g, 81%);
mp 109–1108C; 1H NMR (CDCl3) d 2.36 (s, 3H), 3.76 (s, 3H), 3.87
(s, 3H), 3.88 (d, 2H, J ¼ 6.3 Hz), 3.94 (s, 3H), 5.01 (t, 1H, J ¼ 6.3 Hz),
6.41 (s, 1H), 7.23 (d, 2H, J ¼ 8.1 Hz), 7.62 (s, 1H) and 7.75 (d, 2H,
J ¼ 8.1 Hz); 13C NMR (CDCl3) d 21.5, 55.9, 56.8, 60.6, 66.4, 68.7, 92.9,
114.6, 119.5, 124.1, 127.2 (2C), 129.5 (2C), 129.9, 131.2, 136.4, 144.2,
147.7, and 150.6; IR (CHCl3) 3416 cm21
;
MS (ESþ) m/z 404
(M 2 H2O þ H). Anal. calcd. for C20H23NO7S: C, 57.00; H, 5.50; N, 3.32.
Found: C, 56.89; H, 5.32; N, 3.26.

Total Synthesis of Secobatzelline B
2405
2-Acetoxy-2-(4,6,7-trimethoxy-1-tosylindol-3-yl)ethyl acetate (10)
To a solution of compound 9 (0.80 g, 1.9 mmol) in anhydrous dichloro-
methane (25 mL) at 08C, triethyl amine (1.32 mL, 9.5 mmol), DMAP (2–3
crystals), and acetic anhydride (0.7 mL, 9.5 mmol) were added. The
reaction mixture was then stirred at room temperature for 1 h. TLC examin-
ation (ethyl acetate/hexanes, 2:3) indicated the completion of the reaction.
The reaction mixture was then diluted with dichloromethane (25 mL) and
washed with water (3 ꢀ 20 mL) and brine (1 ꢀ 20 mL). The organic layer
was dried over Na2SO4 and filtered, and the solvent was completely
removed under vacuum to obtain the crude product, which was purified by
column chromatography over silica gel (10 ꢀ 3 cm) using ethyl acetate/
1
hexanes (2:3) to afford the pure product 10 (0.92 g, 96%); oil; H NMR
(CDCl3) d 2.09 (s, 3H), 2.18 (s, 3H), 2.36 (s, 3H), 3.75 (s, 3H), 3.85
(s, 3H), 3.86 (s, 3H), 4.25 (dd, 1H, J1 ¼ 2.9 Hz, J2 ¼ 11.9 Hz), 4.65 (dd,
1H, J1 ¼ 7.3 Hz, J2 ¼ 11.9 Hz), 6.35 (s, 1H), 6.52–6.58 (m, 1H), 7.23
(d, 2H, J ¼ 8.2 Hz), 7.62 (s, 1H) and 7.72 (d, 2H, J ¼ 8.2 Hz). 13C NMR
(CDCl3) d 20.8, 21.1, 21.5, 55.5, 56.7, 60.6, 65.4, 68.1, 92.7, 113.9, 116.1,
124.2, 127.2 (2C), 129.4, 129.5 (2C), 130.6, 136.3, 144.2, 148.9, 150.8,
170.0, and 170.5; IR (CHCl3) 1742 cm21; MS (ESþ) m/z 446 (M – OAc).
Anal. calcd. for C24H27NO9S: C, 57.02; H, 5.38; N, 2.77. Found: C, 56.80;
H, 5.21; N, 2.70.
3-(1,2-Diacetoxyethyl)-6-methoxy-1-tosylindole-4,7-dione (11)
To a solution of diacetate 10 (1.92 g, 3.8 mmol) in anhydrous dichloro-
methane (150 mL), tetrabutyl ammonium hydrogen sulfate (2.58 g,
7.6 mmol) and ceric ammonium nitrate (4.17 g, 7.6 mmol) were added and
stirred for 5 min at room temperature. To the reaction mixture was then
added 1 drop of water, and stirring continued for 5 min. After every 5 min,
1 drop of water was added. After adding about 8 drops of water, the
reaction mixture was stirred at room temperature and monitored by TLC
(ethyl acetate/hexanes, 2:3) for completion. It required 4–5 h of stirring at
room temperature for completion of the reaction as indicated by TLC. Con-
trolled addition of water is crucial for this experiment as excess water can
lead to the formation of by-products. The inorganic solids were filtered and
washed with dichloromethane (50 mL). The organic layer was then washed
with water (2 ꢀ 50 mL) and brine (1 ꢀ 50 mL). The organic layer was
dried over Na2SO4 and filtered, and the solvent was removed under vacuum
to obtain the crude product, which was purified by column chromatography
over silica gel (20 ꢀ 4 cm) using ethyl acetate/hexanes (2:3) to afford the
1
pure product 11 as a yellow solid (1.17 g, 65%); mp 152–1548C; H NMR
(CDCl3) d 2.07 (s, 3H), 2.18 (s, 3H), 2.43 (s, 3H), 3.79 (s, 3H), 4.35–4.45
(m, 2H), 5.75 (s, 1H), 6.50 (t, 1H, J ¼ 4.3 Hz), 7.35 (d, 2H, J ¼ 8.4 Hz),

2406
B. A. Shinkre and S. E. Velu
7.81 (s, 1H) and 8.03 (d, 2H, J ¼ 8.4 Hz); 13C NMR (CDCl3) d 20.5, 20.8,
21.6, 56.8, 64.1, 66.8, 106.4, 121.1, 127.0, 128.2, 129.1 (2C), 129.6 (3C),
132.9, 146.4, 159.3, 168.9, 169.4, 170.2, and 182.7; IR (CHCl3) 1647,
1682, 1744 cm21; MS (ESþ) m/z 416 (M 2 OAc). Anal. calcd. for
C22H21NO9S: C, 55.57; H, 4.45; N, 2.95. Found: C, 55.61; H, 4.38; N, 3.02.
3-(1,2-Diacetoxyethyl)-5-chloro-6-methoxy-1-tosylindole-4,7-dione (12)
To a solution of quinone 11 (0.095 g, 0.2 mmol) in ethyl acetate (15 mL) and
water (1.5 mL), solid NaCl (2.92 g, 50 mmol) was added and stirred at room
temperature for 10 min. To the reaction mixture, oxone (0.984 g, 1.6 mmol)
was then added and stirred at room temperature for 30 min. TLC examination
(ethyl acetate/hexanes, 1:3) revealed that the reaction was complete. The
reaction mixture was then diluted with ethyl acetate (20 mL) and washed
with water (3 ꢀ 15 mL). The organic layer was dried over Na2SO4 and
filtered, and the solvent was completely removed under vacuum to obtain
the crude product, which was purified by column chromatography over
silica gel (20 ꢀ 2 cm) using ethyl acetate/hexanes (1:3) to afford the pure
product 12 (0.046 g, 45%); oil; 1H NMR (CDCl3) d 2.06 (s, 3H), 2.18
(s, 3H), 2.46 (s, 3H), 4.14 (s, 3H), 4.40 (d, 2H, J ¼ 4.5 Hz), 6.46 (t, 1H,
J ¼ 4.5 Hz), 7.38 (d, 2H, J ¼ 8.2 Hz), 7.79 (s, 1H) and 8.02 (d, 2H,
J ¼ 8.2 Hz); 13C NMR (CDCl3) d 20.7, 21.0, 21.8, 61.9, 64.1, 67.0, 122.0,
125.6, 125.8, 128.2, 128.3, 129.2 (2C), 129.9 (2C), 133.0, 146.9, 155.4,
168.8, 169.6, 170.4, and 176.2; IR (CHCl3) 1595, 1677, 1745 cm21; MS
(ESþ) m/z 450 (M 2 OAc). Anal. calcd. for C22H20ClNO9S: C, 51.82; H,
3.95; N, 2.75. Found: C, 51.53; H, 3.87; N, 2.78.
3-(1,2-Diacetoxyethyl)-6-amino-5-chloro-1-tosylindole-4,7-dione(13)
To a solution of quinone 12 (0.050 g, 0.1 mmol) in ethanol (12 mL), aqueous
ammonium hydroxide (2.0 mL) was added and stirred at room temperature for
4 h. TLC examination (ethyl acetate/hexanes, 2:3) revealed that the reaction
is complete. The solvent was completely removed under vacuum. The residue
was dissolved in dichloromethane (30 mL) and washed with water
(1 ꢀ 15 mL) and brine (1 ꢀ 15 mL). The organic layer was dried over
Na2SO4 and filtered, and the solvent was removed under vacuum to obtain
the crude product, which was purified by column chromatography over
silica gel (20 ꢀ 2 cm) using ethyl acetate/hexanes (2:3) to afford the
product 13 (0.028 g, 58%); oil; 1H NMR (CDCl3) d 2.06 (s, 3H), 2.18
(s, 3H), 2.46 (s, 3H), 4.36–4.47 (m, 2H), 5.40 (br s, 2H), 6.52 (t, 1H,
J ¼ 5.1 Hz), 7.37 (d, 2H, J ¼ 8.5 Hz), 7.79 (s, 1H), and 7.98 (d, 2H,
J ¼ 8.5 Hz); 13C NMR (CDCl3) d 20.8, 21.0, 21.8, 64.4, 67.2, 108.0, 122.7,
126.7, 127.9, 128.9, 129.0 (2C), 129.9 (2C), 133.1, 144.0, 146.8, 167.8,

Total Synthesis of Secobatzelline B
2407
169.6, 170.5, and 174.9; IR (CHCl3) 1614, 1683, 1744, 3386 cm21; MS (ESþ)
m/z 493 (M – H). Anal. calcd. for C21H19ClN2O8S: C, 50.97; H, 3.87; N, 5.66.
Found: C, 51.27; H, 4.16; N, 5.37.
Secobatzelline B (2)
To a solution of aminoquinone 13 (0.020 g, 0.04 mmol) in anhydrous
methanol (8 mL) at 08C, sodium methoxide (0.032 g, 0.6 mmol) was added
and stirred for 30 min. The reaction mixture was further stirred at room temp-
erature for 2 h. It was then cooled to 08C and quenched by dropwise addition of
water (10 drops). Solvent was completely removed under vacuum, and residue
was purified by column chromatography over silica gel (10 ꢀ 1.5 cm) using
methanol/chloroform (1:9) to afford pure product Secobatzelline B (2)
(0.009 g, 86%). 1H NMR (10% DMSO-d6-CD3COCD3) d 3.43–3.52
(m, 1H), 3.60–3.70 (m, 1H), 4.20 (t, 1H, J ¼ 5.4 Hz), 4.85–4.95 (m, 1H),
5.03 (d, 1H, J ¼ 6.0 Hz), 6.84 (br s, 1H), 7.18 (s, 1H), and 12.56 (br s, 1H);
13C NMR (10% DMSO-d6 in acetone-d6) d 67.3, 69.0, 106.7, 123.9, 126.8,
128.8, 129.9, 146.5, 170.4, and 177.2; MS (ESþ) m/z 255 (M 2 H).
ACKNOWLEDGMENTS
Authors acknowledge the financial support from the Breast Spore pilot grant
from the University of Alabama at Birmingham (UAB). S.V. also acknowl-
edges the financial support from a faculty development grant from UAB
Faculty development program (FGDP).
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