A total synthesis of the antibiotic DB-2073

Article abstract of DOI:10.1081/SCC-120023438

A convergent aromatic annulation strategy based on the Michael addition of the dimethyl-1,3-acetonedicarboxylate 1 anion to 2-hexynal 2, followed by a regiocontrolled Dieckmann-type cyclization, has been applied to a total synthesis of the antibiotic, DB-2073 I. This tandem annulation reaction generates the fully substituted aromatic intermediate 3, which was transformed by a five-step sequence to I.

Full text of DOI:10.1081/SCC-120023438

This article was downloaded by: [Fordham University]
On: 02 October 2013, At: 09:07
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
A Total Synthesis of the Antibiotic DB-2073
Adrián Covarrubias-Zúñiga a , José G. Avila-Zárraga b & David Arias Salas a
a Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria,
Coyoacán, México
b Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria,
Coyoacán, México
Published online: 17 Aug 2006.
To cite this article: Adrián Covarrubias-Zúñiga , José G. Avila-Zárraga & David Arias Salas (2003) A Total Synthesis of the
Antibiotic DB-2073, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 33:18, 3173-3181, DOI: 10.1081/SCC-120023438
To link to this article: http://dx.doi.org/10.1081/SCC-120023438
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 18, pp. 3173–3181, 2003
A Total Synthesis of the Antibiotic DB-2073
2
Adrian Covarrubias-Zuniga,1, Jose G. Avila-Zarraga, and
*
David Arias Salas1
2
1Instituto de Quımica, and Facultadde Quı mica,
Universidad Nacional Autonoma de Mexico,
Ciudad Universitaria, Coyoacan, Mexico
ABSTRACT
A convergent aromatic annulation strategy basedon the Michael
addition of the dimethyl-1,3-acetonedicarboxylate 1 anion to 2-hex-
ynal 2, followedby a regiocontrolledDieckmann-type cyclization,
has been appliedto a total synthesis of the antibiotic, DB-2073 I.
This tandem annulation reaction generates the fully substituted
aromatic intermediate 3, which was transformedby a five-step
sequence to I.
*Correspondence: Adrian Covarrubias-Zuniga, Instituto de Quımica, Universi-
dad Nacional Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria,
Coyoacan 04510, Mexico; E-mail: adriancz@servidor.unam.mx.
3173
DOI: 10.1081/SCC-120023438
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3174
Covarrubias-Zuniga, Avila-Zarraga, and Salas
In recent years we have developed a total and a formal synthesis of
mycophenolic acid[Covarrubias-Zu niga, A.; Gonzalez-Lucas, A.
Tetrahedron Lett. 1998, 39, 2881; Covarrubias-Zuniga, A.; Dıaz-
Domınguez, J.; Olguın-Uribe, J.S. Synthetic Communications
2001, 31, 1373.] using as key step tandem reactions based on
Michael addition and intramolecular Dieckmann-cyclization; In
this article we utilize this synthetic approach for the total synthesis
of the resorcinol DB-2073 I. This tetrasubstitutedresorcinol was
isolatedandpurifiedfrom pseudomonas B-9004, showing antibacte-
rial andantifungal activities [Kanda, N.; Ishizaki, N.I.; Oshima, M.;
Handa, A.; Kitahara, T.J. Antibiotics 1975, 28, 935.]. The molecular
formula of DB-2073 was establishedby spectroscopic methosd
[Kitahara, T.; Kanda, N. J. Antibiotics 1975, 28, 943.], as 2-hexyl-
5-propyl-resorcinol I.
Key Words:
DB-2073 was first synthetizedby Danheiser [5] using an elegant regio-
controlledannulation approach to highly substitutedresorcinols based
on a thermal-photochemical step combination of alkynyl ethers andvinyl
ketenes derived from cyclobutenones. A second synthesis has been devel-
oped by Kotnis starting from 5-propyl-1,3-cyclohexanedione with iodine
in refluxing methanol.[6]
OH
n-hex
HO
I
RESULTS AND DISCUSSION
Our approach involves the Michael addition of the 2-hexyl-1,3-
dimethyl-acetone-dicarboxylate 1 anion to 2-hexynal (2) andintramolec-
ular Dieckmann-cyclization followedby spontaneous aromatization
(Sch. 1) to produce the hexasubstituted resorcinol (3) in 25% yield.
Compound 1 was preparedin three steps: formation of the enol
methyl ether of 1,3-dimethyl acetone dicarboxylate, alkylation with

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Antibiotic DB-2073
3175
O
O
n-hex
CO Me
2
n-hex
THF
Ar
CO Me
2
CHO
+
Me OC
Na
2
CO Me
2
2
Michael
Na
CHO
Dieckmann
CO2Me
O
OH
n-hex
O
n-hex
HO
-MeOH
CO2Me
+
H
aromatization
Na
MeO
CHO
CHO
3
Scheme 1.
OMe
OMe
n-hex
n-hex
MeO
CO2Me
CO2Me
3
MeO
CHO
CO2H
5
4
OMe
OMe
n-hex
MeO
n-hex
MeO
CO2H
I
CO2H
7
6
Scheme 2.
1-iodohexane in dry DMF and hydrolysis with a mixture of HCO2H-
hexane.[7] Aldeyde 2 was preparedaccording to the methodreportedby
Brandsma.[8] With compound 3 at hand, the completion of this synthesis
was accomplishedby employing the five-step sequence shown in Sch. 2.
Methylation of resorcinol 3 with NaH andMeI in rdy DMF gave

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3176
Covarrubias-Zuniga, Avila-Zarraga, and Salas
compound 4 in 90% yieldandthe subsequent oxidation of the formyl
group with Jones reagent[9] in acetone gave acid 5 in 82% yieldpresum-
ably for steric reasons it was necessary to modify the standard conditions
of Jones oxidation from 0ꢀC or room temperature to 40ꢀC. 5 was hydro-
lyzed under vigorous conditions with KOH in an ethylene glycol–water
mixture (6:4) to give compound 6 in 90% yield. The diacid 6 was
decarboxylated with CuO/quinoline[10] at 125ꢀC over argon atmosphere
in 54% yield. Finally the demethylation was accomplished employing
trimethylsilyl iodide[11] in acetonitrile under reflux, furnished DB-2073
as colorless crystals, m.p. 86–88ꢀC (Lit.[2] m.p. 86–88ꢀC) with properties
identical to the natural compound.
In conclusion, the synthesis reportedherein highlights the utility of
our aromatic regiocontrolledannulation methodas an efficient methodin
the synthesis of polysubstituedaromatic compounds. This convergent
route, delivers resorcinol I in five steps from 3 (8% overall yield). The
application of this methodology to other natural product synthesis is in
progress andwill be reportedin due course.
EXPERIMENTAL SECTION
Melting points are uncorrected. Thin-layer chromatography was
performedon silica gel 60 F
andvisualizedby UV irraadtion.
254
1H NMR spectra were recorded either at 200 or 300 MHz; while
13C NMR spectra were run at 75 MHz in CDCl3 solution. Mass spectra
were measuredat 70 eV (EI). Elemental analyses were performedby
Galbrait Laboratories, Inc.; column chromatography purifications were
carriedout using gel (70–230 mesh).
E-Methyl-4-carbomethoxy-3-methoxy-2-butenoate[12]
A mixture of 50 g of 1,3-dimethyl acetonedicarboxylate (0.28 mol,
42 mL, 97%), 400 mL of dry methanol, 18.8 g (0.177 mol) of trimethyl
orthoformiate and0.1 g of p-TsOH were refluxed40 h. The mixture was
pouredover 0.5 of Na CO3 in 300 mL of water andextractedwith ethyl
2
acetate (3 ꢁ 100 mL). The combined organic phase was dried over anhyd.
Na2SO4 and concentrated. The residue was purified by column chro-
matography (750 g of silica gel) andmethyl-4-carbomethoxy-3-methoxy-
2-butenoate III (49.8 g, 95% yield) was eluted using 5% ethyl acetate in
hexane. IR (neat) 1142, 1119, 1633, 1712, 1745, and2953 cm ꢂ1. 1H NMR

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Antibiotic DB-2073
3177
ꢀ ppm 3.68 (s, 3H), 3.69 (s, 3H), 3.71 (s, 3H), 3.84 (s, 2H), 5.20 (s,
1H). 13C NMR ꢀ ppm 38.10, 50.98, 52.06, 55.90, 92.95, 167.66, 168.05.
169.45. MS (EI) m/z (relative intensity) 188 (Mþ, 24), 157 (100), 156
(46), 125 (55). Anal. calcd. for C8H12O5: C, 51.06%; H, 6.38. Found:
C, 51.10; H, 6.36.
E-Methyl-4-carbomethoxy-4-hexyl-3-methoxy-2-butenoate[12]
To 2.34 g of NaH (58 mmol, 60%) in dry DMF (130 mL) was
dropped 13.3 g (49 mmol of methyl-4-carbomethoxy-2-butenoate, 17.7 g
(73.5 mmol) of 1-iodohexane was added and the mixture was stirred 36 h
at 40ꢀC. The mixture was pouredin 650 mL of water andextractedwith
ethyl acetate 4 ꢁ 50 mL. The organic phase was washedwith H 2O
2 ꢁ 25 mL, dried over Na2SO4, and concentrated. The residue was sub-
jectedto column chromatography (eluant ethyl acetate: hexane 4: 96,
300 g of silica gel) affording methyl-4-carbomethoxy-4-hexyl-3-meth-
oxy-2-butenoate (9.58 g, 76% yield). IR (neat) 1146, 1197, 1631, 1715,
1
1744, 2859 cmꢂ1. H NMR ꢀ ppm 0.88 (t, 3H, J ¼ 6.9 Hz), 1.15–1.35 (m,
8H), 1.65–2.05 (m, 2H), 3.65 (s, 3H), 3.67 (s, 3H), 3.69 (s, 3H), 4.93
(dd, 1H, J ¼ 6.38 Hz and J ¼ 6.26 Hz). 13C NMR ꢀ ppm 14.01, 22.54,
29.01, 31.57, 31.58, 46.03, 50.97, 52.02, 55.83, 90.92, 92.44, 167.64,
171.73, 171.98; MS (EI) m/z (relative intensity) 272 (Mþ, 13), 169
(100), 156 (98), 128 (68), 241 (48). Anal. calcd. for C14H24O5: C, 61.69;
H, 8.81. Found: C, 61.71; H, 8.79.
2-Hexyl-1,3-dimethyl Acetonedicarboxylate (1)
Methyl-4-carbomethoxy-4-hexyl-3-methoxy-2-butenoate
(15 g,
55.14 mmol), HCO2H (50 mL, ꢃ1.15 mol) andhexane (50 mL) were
ꢀ
stirredto 35 C for 36 h. The mixture reaction was pouredin 200 mL of
water andextractedwith ether (3 ꢁ 120 mL). The organic layer was sepa-
rated, washed with water (3 ꢁ 50 mL) andNa 2CO3 (5 g) in 50 mL of
water, dried Na2SO4 filtered, and concentrated. The residue was purified
by column chromatography (eluant ethyl acetate: hexane, 5:95, 300 g of
silica gel) affording 1 (12.1 g, 85% Yield). IR (neat) 1660, 1747,
1
2859 cmꢂ1. H NMR ꢀ ppm 0.87 (t, 3H, J ¼ 6.9 Hz), 1.10–1.18 (m, 8H),
1.63–1.91 (m, 2H), 3.57–3.66 (m, 3H), 3.73 (s, 6H). 13C NMR ꢀ ppm
13.88, 22.40, 27.14, 28.04, 28.86, 31.37, 47.76, 52.29, 58.76, 90.43, 167.07,
169.75, 197.53. MS (EI) m/z (relative intensity) 272 (Mþ, 13), 169 (100),

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3178
Covarrubias-Zuniga, Avila-Zarraga, and Salas
156 (98), 128 (68), 241 (48). Anal. calcd. for C14H24O5: C, 60.46; H, 8.52.
Found: C, 60.49; H, 8.50.
Methyl-3-formyl-5-hexyl-4,6-dihydroxy-2-propylbenzoate (3)
(4 g, 15.5 mmol) of 1 were added dropwise to a suspension of
NaH (60%, 0.87 g, 21.7 mmol) in dry THF (40 mL) with magnetic stir-
ring. To the resulting solution with argon atmosphere 2-hexynal 1.94 g
(20 mmol) were added and, after 0.5 h, the mixture was poured into
dilutedHCl (15 mL). The organic layer was separatedandthe aqueous
phase washed with brine (25 mL), dried over anhyd. Na2SO4 andcon-
centrated. The residue was subjected to column chromatography, the
resorcinol 3 (1.25 g, 25%) being elutedwith 5% ethyl acetate in hexane
(120 g of silica gel): IR (neat) 1632, 1660, 1727, 2857, 2958, 3360 cmꢂ1
.
1H NMRꢀ ppm 0.60–2.00 (m, 16H), 2.62 (t, J ¼ 7.9, 2H), 3.11–3.16(m, 2H),
3.98 (s, 3H), 10.19 (s, 1H), 12.09 (s, 1H), and13.10 (s, 1H). 13C NMR
ꢀ ppm 14.1, 14.45, 22.15, 26.81, 28.33, 29.49, 29.73, 31.01, 31.82, 52.69,
106.09, 112.62, 116.00, 151.21, 166.02, 166.37, 171.73, 194.23. MS m/z
(relative intensity) 322 (Mþ, 44), 219 (100), 290 (18), 251 (18). Anal.
calcd. for C18H26O5: C, 67.08; H, 8.07. Found: C, 67.22; H, 8.10.
Methyl-3-formyl-5-hexyl-4,6-dimethoxy-2-propylbenzoate (4)
3 (0.6 g, 1.86 mmol) was dissolved in dry DMF (12 mL) and NaH
(89 mg, 2.23 mmol, 60%) was added portionwise with stirring. MeI
(0.3 mL, 4.80 mmol) was added and stirring continued for 1.5 h. NaH
(89 mg, 2.23 mmol, 60%) and MeI (0.3 mL, 4.80 mmol) were added and
stirring continuedfor 3 h the reaction mixture was pouredinto water
(50 mL) andextractedwith ether (3 ꢁ 20 mL). The organic layer was
separated, washed with water (10 mL), dried (Na2SO4), filtered, and con-
centrated. The residue was purified by column chromatography ( eluant
ethyl acetate:hexane, 0.3:9.7, 18 g of silica gel) affording 4 (587 mg, 90%).
IR (neat) 1632, 1661, 2857 cmꢂ1 1H NMR ꢀ ppm 0.82–1.05 (m, 2H),
.
1.20–1.70 (m, 10H), 2.54–2.65 (m, 2H), 2.72–2.82 (m, 2H), 3.83 (s, 3H),
3.84 (s, 3H), 3.93 (s, 3H), 10.40 (s, 1H). 13C NMR ꢀ ppm 14.04, 14.53,
22.56, 24.12, 24.92, 29.78, 30.00, 31.54, 32.77, 52.36, 62.42, 64.32, 123.93,
126.97, 128.54, 142.44, 160.43, 165.29, 168.37, 191.22. MS m/z (relative
intensity) 350 (Mþ, 40), 318 (17), 279 (16), 247 (100). Anal. calcd. for
C20H30O5: C, 68.48; H, 8.56. Found: C, 68.72; H, 8.53.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Antibiotic DB-2073
3179
3-Carbomethoxy-5-hexyl-4,6-dimethoxy-2-propyl
Benzoic Acid (5)
4 (0.4 g, 1.14 mmol) was dissolved in acetone (6 mL) and 2 mL of
Jones Reagent[9] was added with stirring. The reaction mixture was
heated(40–50 ꢀC) for 5 h, andthen pouredinto water (30), extracted
with ether (4 ꢁ 15 mL). The organic layer was separated, dried
(Na2SO4), filtered, and concentrated. The residue was purified by
column chromatography (eluant ethyl acetate:hexane, 15:85) affording
5 (343 mg, 82%). IR: 1160, 1575, 1704, 1734, 2872, 3210 cmꢂ1
.
1H NMR ꢀ ppm 0.84–1.02 (m, 6H), 1.20–1.80 (m, 10H), 2.54–2.68
(m, 4H), 3.81 (s, 3H), 3.86 (s, 3H), 3.93 (s, 3H), 3.50–4.00 (bs, 1H).
13C NMR ꢀ ppm 14.05, 14.47, 22.57, 24.57, 24.76, 29.85, 29.90, 31.53,
33.45, 52.36, 62.56, 62.86, 123.82, 125.72, 128.33, 137.67, 157.76, 168.36,
171.26. MS m/z (relative intensity) 366 (Mþ, 100), 335 (54), 295 (78).
Anal. calcd. for C20H30O6: C, 65.57; H, 8.19. Found: C, 65.92; H, 8.09.
4,6-Dimethoxy-5-hexyl-2-propyl-1,3-benzenodioic Acid (6)
5 (80 mg, 0.218 mmol) was dissolved in ethylene glycol (1.6 mL),
KOH (120 mg) in water (1.1 mL) was aꢀdded and Ar was bubbled. The
reaction mixture was heatedto 115–120 C for 2 h, cooledat room tem-
perature, andpouredinto water (10 mL), extractedwith ether
(2 ꢁ 10 mL). The aqueous layer was separatedandacidifiedto pH 4
with aqueous HCl (10%), extractedwith ether (4 ꢁ 10 mL), the organic
layer were separated, dried (Na2SO4), filtered, and concentrated. The
residue was purified by column chromatography (eluant ethyl acetate:
hexane, 20:80) affording 6 (69 mg, 90%). IR: 1574, 1704, 2930,
1
3403 cmꢂ1. H NMR 0.70–1.00 (m, 6H), 1.15–1.70 (m, 10H), 2.45–2.70
(m, 4H), 3.66 (s, 3H), 3.77 (s, 3H), 4.70-5.15 (bs, 2H). 13C NMR ꢀ ppm
13.98, 14.34, 22.48, 24.49, 24.77, 29.77, 29.84, 31.44, 33.44, 62.69, 125.13,
128.23, 136.97, 157.35, 170.93. MS m/z (relative intensity) 352 (Mþ, 99),
221 (100), 337 (60), 263 (40). Anal. calcd. for C20H30O6: C, 68.18; H, 8.52.
Found: C, 68.22; H, 8.50.
2-Hexyl-5-propyl-1,3-dimethoxybencene (7)
6 (60 mg, 0.17 mmol), dry quinoline (1 mL) and CuO (22 mg), were
heatedunedr argon atmosphere to 215 ꢀC for 15 min. The reaction
mixture was cooledat room temperature andpouredinto aqueous HCl

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
3180
Covarrubias-Zuniga, Avila-Zarraga, and Salas
(5 mL, 10%) extractedwith ether (3 ꢁ 10 mL), the organic layer was
separated, dried (Na2SO4), filtered, and concentrated. The residue was
purifiedby column chromatography (eluant ethyl acetate:hexane, 1: 99)
1
affording 7 (25 mg, 55.6%). IR: 1575, 2872, 2957 cmꢂ1. H NMR ꢀ ppm
0.80–1.10 (m, 6H), 1.20–1.80 (m, 10H), 2.50–2.70 (m, 4H), 3.79 (s, 6H),
6.36 (s, 2H). MS m/z (relative intensity) 264 (Mþ, 41), 193 (100), 133 (12).
Anal. calcd. for C17H28O2: C, 77.27; H, 10.60. Found: C, 77.55; H, 10.24.
2-Hexyl-5-propyl-1,3-bencenediol (I)
7 (50 mg, 0.189 mmol) was dissolved in dry acetonitrile (3 mL) and
NaI (142 mg, 0.945 mmol) andMe 3SiCl (103 mg, 0.947 mmol) were added
with stirring. The reaction mixture was refluxedunder Ar atmosphere for
48 h. the reaction mixture was pouredinto H O (10 mL) andextracted
2
wih ether (3 ꢁ 10 mL). Drying, filtration, andconcentration of the
organic layer gave an oily residue that was purified by column chroma-
tography using ethyl acetate:hexane (1:99) as eluant I (40 mg) was
obtainedin 89% yield.
ACKNOWLEDGMENTS
This research was supportedby a Grant-in-Aidfor Scientific
Research No. 27610-E from CONACYT, Mexico. The authors thank
Dr. N. Zuniga for helpful discussions, We thank Messrs. R. Gavino,
R. Patino, L. Velasco, andF. J. Pe rez for running the spectra.
REFERENCES
1. Covarrubias-Zuniga, A.; Gonzalez-Lucas, A. Tetrahedron Lett.
1998, 39, 2881.
2. Covarrubias-Zuniga, A.; Dıaz-Domınguez, J.; Olguın-Uribe, J.S.
Synthetic Communications 2001, 31, 1373.
3. Kanda, N.; Ishizaki, N.I.; Oshima, M.; Handa, A.; Kitahara, T.J.
Antibiotics 1975, 28, 935.
4. Kitahara, T.; Kanda, N. J. Antibiotics 1975, 28, 943.
5. Danheiser, R.L.; Gee, S.K. J. Org. Chem. 1984, 49, 1672.
6. Kotnis, A.S. Tetrahedron Lett. 1991, 29, 3441.
7. Barbot, F.; Miginiac, P. Synthesis 1983, 651. In our case hexane was
substitutedby pentane andthe HCO 2H contained12% of H O.
2

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
Antibiotic DB-2073
3181
8. Brandsma, L.; Verkruijsse, H.D. Synthesis of Acetylenes, Allenes and
Cumulenes; Elsevier Scientific Publishing Company: Netherlands,
1981; 101–102.
9. Bowers, A.; Halsall, T.G.; Jones, E.R.H.; Lemin, A.J. J. Chem. Soc.
1953, 22, 2548.
10. (a) Cohen, T.; Schambach, R.A. J. Am. Chem. Soc. 1970, 92, 3189.
(b) Cairncross, A.; Roland, J.R.; Henderson, R.M.; Sheppard, W.A.
J. Am. Chem. Soc. 1970, 92, 3187.
11. Olah, G.A.; Narang, S.C.; Gupta, B.G.; Malhurta, R. J. Org. Chem.
1979, 44, 1247.
12. The stereochemistry was assignedby 1H NMR analysis of other
isomeric compounds, Methyl-4-carbomethoxy-4-alkyl-3-methoxy-
2-butenoates andby X-ray analysis of E-Methyl-4-carbomethoxy-
4-isopropyl-3-methoxy-2-butenoate (unpublishedresults).
Receivedin the USA December 18, 2002

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.