Synthesis of the tetronate-containing core structure of the antibiotic abyssomicin C

Article abstract of DOI:10.1055/s-2004-837208

The core structure of abyssomicin C (1) containing an oxabicyclooctanone ring and a tetronate was prepared from the addition product of lithium ethyl propiolate and 4-tert-butyldimethylsilyloxycyclohexanone. Tetronate formation via addition of sodium methanolate followed by hydrolysis gave the hydroxy tetronic acid 27. The spiro compound 27 could be cyclized to the tricyclic tetronate 23 by a transannular Mitsunobu lactonization. Alternatively, 27 could be prepared from the cyanohydrin cis-19.

Full text of DOI:10.1055/s-2004-837208

314
LETTER
Synthesis of the Tetronate-Containing Core Structure of the Antibiotic
Abyssomicin C
Synthesis
e
of the
A
bys
a
somicin Co
n
re Structure-Philippe Rath, Martin Eipert, Stephan Kinast, Martin E. Maier*
Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
Fax +49(7071)295137; E-mail: martin.e.maier@uni-tuebingen.de
Received 12 November 2004
13
Me
O
Me
H
H
Abstract: The core structure of abyssomicin C (1) containing an
oxabicyclooctanone ring and a tetronate was prepared from the ad-
dition product of lithium ethyl propiolate and 4-tert-butyldimethyl-
silyloxycyclohexanone. Tetronate formation via addition of sodium
methanolate followed by hydrolysis gave the hydroxy tetronic acid
27. The spiro compound 27 could be cyclized to the tricyclic
tetronate 23 by a transannular Mitsunobu lactonization. Alterna-
tively, 27 could be prepared from the cyanohydrin cis-19.
HO
HO
O
O
O
16
4
H
H
2
O
1
N
8
O
O
O
O
O
HO
Me
Me
Me
Me
Key words: bicyclics, cyanohydrins, Mitsunobu, ring closure,
Wittig reactions
abyssomicin C (1)
abyssomicin B (2)
Figure 1 Structures of two important abyssomicins.
The increasing resistance of gram-positive bacteria
against classical antibiotics demonstrates the necessity for
finding new molecular targets and lead structures. In this
regard, the inhibition of biosynthesis pathways that are
exclusive for microorganisms seems particularly attrac-
tive. Recently, the group of R. Süssmuth described the
abyssomicins which are natural products with unprece-
dented structures (Figure 1).1,2 The abyssomicins are
polyketide-type structures containing a highly functional-
ized cyclohexane ring with a spiro-tetronate subunit. The
spiro-tetronic acid bridges the cyclohexane ring resulting
in a tetronate and an oxabicyclo[2.2.2]octane ring. Anoth-
er bridge extends from the tetronate to the cyclohexane
ring. Among the three natural products abyssomicin C is
the active one and it inhibits Staphylococcus aureus al-
ready at a concentration of 4 mg/mL. It is believed that the
enone system, which is part of abyssomicin C, functions
as a Michael acceptor. The abyssomicins were discovered
during the screening of rare antinocycetes for the inhibi-
tion of the p-aminobenzoate (pABA) biosynthesis. Be-
cause of the unique structural features and the interesting
biological activity we initiated a program aimed at the to-
tal synthesis of abyssomicin C. In this paper we describe
the synthesis of the core structure of abyssomicin C using
a transannular Mitsunobu reaction.
precursor of structure 5 could be a bicyclic lactone (cf. 6)
or a spiro tetronate (cf. 7). While bicyclic lactones are ac-
cessible,3 their tendency to undergo lactone opening
makes this approach somewhat less attractive. On the
other hand, this strategy might be advantageous for the
introduction of substituents or for controlling relative
stereochemistry en-route to a spiro tetronate.4 If one looks
at the spiro tetronate A88696F5,6 (8) the similarity to abys-
somicin C is striking. Accordingly, the spiro tetronic acid
9 might be a biosynthetic intermediate. A transannular
epoxide opening would lead to abyssomicin C.
Initially, we performed some model studies based on tan-
dem Michael additions.7–9 Thus, the known 1,3-diketone10
10 was converted to the vinylogous ester 11. Treatment of
this ester with LDA at –78 °C followed by the addition of
methyl crotonate gave a good yield of the bicyclooctanone
12 (Scheme 1). However, this structure is lacking the car-
bonyl group at C16. Therefore, the pyrandione 13 was
prepared from 1-bromo-3-phenyl-2-propanone and the
salt of oxalic acid monoester.11 While the tandem Michael
addition of 14 with 15 was possible the yield was moder-
ate. The structure of this compound was supported by an
X-ray analysis (see Chem3D rendering in Scheme 1). Un-
fortunately, attempted cleavage of the methyl ether of 15
led to a complex mixture. In addition, substrate 13 without
the phenyl group is not known. At this point we aban-
doned this approach and focused on the transannular
tetronate formation.
Some retrosynthetic considerations are summarized in
Figure 2. Initially, it might be wise to remove the large
sector that bridges the tetronate and the bicyclooctane. For
the construction of this macrocycle, intramolecular
Horner–Emmons, intramolecular Nozaki, or intramole-
cular acylation of the tetronate can be envisioned. A com-
pound such as 4 should be available from the alkyne 5. A
Starting from 1,4-cyclohexanediol (16) a mono-oxidation
gave 4-hydroxy cyclohexanone12 (17) (Scheme 2). The
alcohol function of 17 was protected as tert-butyldi-
methylsilyl ether giving the cyclohexanone13 18. Among
the nucleophiles that, after addition to a ketone, allow
further transformation to a tetronic acid or tetronate,
SYNLETT 2005, No. 2, pp 0314–0318
0
1.
0
2.
2
0
0
5
Advanced online publication: 17.12.2004
DOI: 10.1055/s-2004-837208; Art ID: G42904ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of the Abyssomicin Core Structure
315
cyanide14,15 and the propiolate anions16 are the most com-
mon ones.17–19 In the event, reaction of the cyclohexanone
18 with Me3SiCN in the presence of catalytic amounts of
ZnI2 followed by acidic work-up gave a 5:1 mixture of the
cis- and trans-diols cis-19 and trans-19.20 In analogy to
the work of Nagao, it was assumed that the major dia-
stereomer is the cis-diol, resulting from axial attack on the
conformer with an axial tert-BuMe2SiO- group.21 This
could be proven by hydrolysis of the major cyanohydrin
cis-19 to the dihydroxy acid 20 followed by a transannular
Mitsunobu lactonization resulting in the lactone 21. Un-
fortunately, a conversion of the bicyclic lactone 21 to the
bicyclic tetronate 23 with the ketene ylide22,23 22 was not
successful, even under forcing conditions.
Me
Me
H
H
HO
HO
O
O
O
O
H
H
Wittig–Horner
X
acylation
O
Nozaki
O
O
O
O
O
4
3
Me
Me
O
Me
O
H
H
H
X
HO
HO
HO
or
OH
O
H
H
H
O
HO
O
O
O
6
5
7
OH
OH
TBSO
Me
H
1. Me3SiCN
ZnI2 (cat.)
O
Et
O
H
KBrO4, CAN
79%
TBSCl
OH
O
OH
imidazole
99%
2. 1 N HCl
O
OH
O
O
OH
16
17
18
O
O
O
OH
OH
OH
Me
Me
concd. HCl
reflux, 81%
A88696F (8)
possible biosynthesis precursor 9
+
Figure 2 Retrosynthetic considerations for the abyssomicins;
X = leaving group or part of epoxide, the methyl groups at C4 and C6
are omitted for simplicity.
HO CN
NC OH
HO CO2H
cis-19 (major)
trans-19
20
22
Ph3P
C
C
O
DEAD, Ph3P
THF, 53%
O
O
MeO
O
O
O
MeOH, pTsOH
LDA, THF, –78 °C
toluene, reflux
O
HO
70%
CO2Me
83%
O
O
O
OTBS
10
11
21
23
O
H
MeO2C
O
18
O
O
small nucleophile
16
MeO
12
Scheme 2 Synthesis of the bicyclic lactone 21 via Mitsunobu
lactonization.
Ph
Ph
O
OMe
O
O
OH
O
CH2N2, THF
84%
LDA, THF, –78 °C
A slight modification of the hydrolysis conditions con-
verted the cyanohydrins to the dihydroxy ester 24
(Scheme 3).15a,24 This compound could be obtained dia-
stereomerically pure after chromatography. After protec-
tion of the secondary hydroxyl goup, heating with the
ketene ylide 22 gave rise to the spiro tetronate 26. Hydro-
lysis of both the silyl ether and the tetronate delivered the
polar hydroxytetronic acid 27. Gratifyingly, stirring this
hydroxy acid with Ph3P and diethyl azodicarboxylate
(DEAD) in THF for 48 hours provided the bicyclic
tetronate 23 in good yield.25,26 The structure of this com-
pound is supported by the 13C spectrum showing the
required seven signals. In the IR the carbonyl resonates
at 1743 cm–1 and the tetronate C–H at 3128 cm–1, respec-
tively.
CO2Me
62%
O
O
13
14
MeO2C
O
O
O
OMe
Ph
15
15
Scheme 1 Bicyclic lactones by tandem Michael additions.
Synlett 2005, No. 2, 314–318 © Thieme Stuttgart · New York

316
J.-P. Rath et al.
LETTER
OTBS
OTBS
OH
OTBS
Li
CO2Et
concd. HCl, MeOH
TBSCl
18
+
19
THF, –78 °C, 94%
imidazole, 95%
70%
HO
OH
HO CO2Me
HO CO2Me
25
24
CO2Et
EtO2C
cis-28 (major)
trans-28
OTBS
OH
22
OTBS
OH
5 N HCl, 60 °C
5 h, 86%
Ph3P
C
C
O
toluene, reflux
72%
MeONa, MeOH
60 °C, 2 h, 64%
2 N HCl
98%
cis-28
OMe
OH
O
O
OMe
OMe
O
O
O
O
26
27
O
O
26
29
DEAD, Ph3P
5 N HCl, 60 °C
5 h, 85%
O
27
23
THF, 23 °C, 48 h
57%
O
O
OTBS
OTBS
23
Li
CO2Me
18
+
Scheme 3 Synthesis of the tricyclic tetronate 23 from the cyano-
hydrins 19.
THF, –78 °C
OMe
O
HO
The tetronate 26 could also be prepared from the pro-
piolate cis-28 which is available by addition of lithium
ethylpropiolate16,27 to the ketone 18 (cis-28/trans-
28 = 9:1, Scheme 4). Stirring of cis-28 with MeONa in
methanol affected Michael addition and lactonization
leading to 26 in 64% yield.28 If one uses the anion of me-
thyl propiolate, the addition to 18 is less clean and repro-
ducible. While the normal addition product 30 is still the
major compound in the mixture, a substantial amount of
the spiro-tetronate 26 was observed. Problems in the addi-
tion reactions of lithium methylpropiolate have been no-
ticed before, but a structure of the side product was not
given.29 Hydrolysis of 26 with 1 N HCl gave the tetronate
29. Stronger acid induced hydrolysis to the hydroxy-
tetronic acid 27.
O
CO2Me
30 (75%, cis/trans = 9:1)
26 (24%)
Scheme 4 Synthesis of the tetronate 23 from the propiolate cis-28.
1H NMR (400 MHz, DMSO): d = 1.47–1.64 [m, 4 H, CH(CH2)2],
1.67–1.79 [m, 2 H, C(CHH)], 1.82–1.92 [m, 2 H, C(CHH)], 3.44–
3.53 (m, 0.2 H, trans CH), 3.54–3.66 (m, 1 H, cis CH), 4.57 (d,
J = 4.0 Hz, 1 H, cis CHOH), 4.66 (d, J = 4.6 Hz, 0.2 H, trans
CHOH), 6.36 (s, 1 H, cis OH), 6.47 (s, 0.2 H, trans OH). 13C NMR
(400 MHz, DMSO): d = 29.46 (C-2, C-6), 33.18 (C-3, C-5), 64.28
(C-4), 66.94 (C-1), 123.14 (C-9). MS (EI, 70eV): m/z (%) = 142.1
(6) [M + H]+, 124.2 (8) [M + H – H2O]+, 115.2 (100) [M + H –
HCN]+, 97. 2 (58) [M + H – HCN – H2O]+. FT-ICR (ESI): m/z calcd
for C7H11NO2Na: 164.06820; found: 164.06790.
In summary, we have shown that it is possible to fashion
the bicyclic tetronate 23 by a transannular Mitsunobu
lactonization of the spiro tetronic acid 27. Further work
will focus on the synthesis of higher functionalized tetron-
ic acids containing a handle for attachment of the macro-
cyclic ring. Also the regiochemistry of the transannular
epoxide opening with a tetronic acid will be studied.
1,4-Dihydroxycyclohexanecarboxylic Acid Methyl Ester (24).
HCl (concd, 35 mL) was added to a solution of cyanohydrin 19
(2.12 g, 15.0 mmol) in MeOH (35 mL). The reaction mixture was
refluxed for 36 h. After cooling, the mixture was extracted with
EtOAc several times until precipitation of NH4Cl appeared. The
combined organic layers were dried with MgSO4, filtered, and the
solvent was removed in vacuo. The residue was purified by flash
chromatography (EtOAc–petroleum ether, 4:1) to yield compound
24 (1.83 g, 70%) as a colorless solid, mp 82–84.5 °C. TLC (EtOAc–
petroleum ether, 4:1): Rf = 0.22. IR (KBr): 3390, 3320, 2954, 2870,
1735, 1446, 1256, 1072, 980, 621 cm–1. 1H NMR (400 MHz, DM-
SO): d = 1.40–1.66 (m, 8 H, CH2), 3.29–3.44 (m, 1 H, CH), 3.60 (s,
3 H, CH3), 4.49 (d, J = 4.6 Hz, 1 H, CHOH), 5.12 (s, 1 H, COH).
13C NMR (400 MHz, DMSO): d = 30.00 (C-2, C-6), 32.42 (C-3, C-
5), 51.65 (C-12), 67.75 (C-4), 71.80 (C-1), 176.53 (C-9). FT-ICR
(ESI): m/z calcd for C8H14O4Na: 197.07843; found: 197.07811.
1,4-Dihydroxycyclohexanecarbonitrile (19).
To a solution of the ketone 18 (8.00 g, 35.0 mmol) in CH2Cl2 (25
mL) was added at 0 °C TMSCN (5.13 mL, 38.5 mmol) and neat
ZnI2 (560 mg, 1.75 mmol). The reaction mixture was stirred for 5 h
at r.t. and some precipitated solid was filtered off. The obtained so-
lution was concentrated in vacuo and the crude product was stirred
for 12 h with HCl (1 N, 100 mL). The aqueous layer was extracted
with EtOAc (3 × 100 mL) and the combined organic layers were
dried with MgSO4 and filtered. The solvent was removed in vacuo.
Flash chromatography (EtOAc–petroleum ether, 1:1) provided pure
compound 19 (3.32 g, 67%) as a colorless solid in a ratio of cis/trans
5:1, mp 121–126 °C. TLC (EtOAc–petroleum ether, 2:1): Rf = 0.3.
4-(tert-Butyldimethylsilanyloxy)-1-hydroxycyclohexane-
carboxylic Acid Methyl Ester (25).
A solution of a-hydroxy ester 24 (696 mg, 4.0 mmol), imidazole
(300 mg, 4.4 mmol), DMAP (24 mg, 0.20 mmol) and TBDMSCl
(663 mg, 4.4 mmol) in DMF (35 mL) was stirred at r.t. for 12 h. The
Synlett 2005, No. 2, 314–318 © Thieme Stuttgart · New York

LETTER
Synthesis of the Abyssomicin Core Structure
317
mixture was poured on aq sat. NaHCO3 (7 mL). After separation of
the phases, the aqueous phase was extracted with Et2O (3 × 30 mL).
The combined organic layers were dried with MgSO4, filtered, and
concentrated in vacuo. Purification of the residue by flash chroma-
tography (EtOAc–petroleum ether, 1:10) provided compound 25
(1.10 g, 95%) as a colorless solid. TLC (EtOAc–petroleum ether,
48 h at r.t. before it was concentrated in vacuo and purified by flash
chromatography (EtOAc–petroleum ether, 1:2) to yield the desired
bicycle 23 (285 mg, 57%) as a colorless solid, mp 79.8–80.3 °C.
TLC (Et2O): Rf = 0.32. IR (KBr): 3128, 2958, 2881, 1743, 1631,
1400, 1246, 1169, 1072, 895, 806, 563 cm–1. 1H NMR (400 MHz,
CDCl3): d = 1.64–1.75 [m, 2 H, (CHH)C], 1.87–1.97 [m, 2 H,
(CHH)CH], 2.10–2.22 [m, 2 H, (CHH)CH], 2.24–2.35 [m, 2 H,
(CHH)C], 4.71 [tt, J = 3.5, 1.8 Hz, 1 H, CH(CH2)2], 4.91 (s, 1 H,
CH). 13C NMR (400 MHz, DMSO): d = 24.71 (C-7, C-11), 27.41
(C-8, C-10), 75.55 (C-6), 77.08 (C-9), 82.95 (C-3), 172.44 (C-2),
185.41 (C-4). MS (FAB, 30 °C): m/z (%) = 355.3 (4) [2 M + Na]+,
333.1 (8) [2 M + H]+, 189.0 (18) [M + Na]+, 166.9 (100) [M + H]+.
FT-ICR (ESI): m/z calcd for C9H10O3Na: 189.05222; found:
189.05224.
1
1:4): Rf = 0.55. H NMR (400 MHz, CDCl3): d = 0.03 [s, 6 H,
Si(CH3)2], 0.86 [s, 9 H, Si(CH3)3], 1.66–1.84 (m, 8 H, CH2), 2.85 (s,
1 H, OH), 3.57–3.69 (m, 1 H, OCH), 3.74 (s, 3 H, CH3). 13C NMR
(400 MHz, CDCl3): d = –4.65 (C-9, C-13), 18.11 (C-14), 25.82 (C-
15, C-18, C-19), 30.54 (C-2, C-6), 33.16 (C-3, C-5), 52.66 (C-17),
69.97 (C-1), 72.57 (C-4), 177.58 (C-11).
8-(tert-Butyldimethylsilyloxy)-4-methoxy-1-oxaspiro[4.5]dec-3-
en-2-one (26).
a) From 25: To a solution of the a-hydroxy acid ester 25 (433 mg,
1.5 mmol) in THF (8 mL) was added the phosphanylidene 22 (544
mg, 1.8 mmol), dissolved in THF (8 mL), and a catalytic amount of
pTsOH (6 mg) at –10 °C. The reaction mixture was stirred at –10 °C
for 1 h and then refluxed for 12 h. The mixture was poured on cold
aq sat. NH4Cl (20 mL) and extracted with Et2O (3 × 30 mL). The
combined organic layers were dried with MgSO4, filtered, and the
solvent removed in vacuo. The crude product was purified by flash
chromatography (Et2O–petroleum ether, 4:1) to yield compound 26
(339 mg, 72%) as a colorless solid, mp 145–150 °C.
[4-(tert-Butyldimethylsilyloxy)-1-hydroxycyclohexyl]pro-
pynoic Acid Ethyl Ester (28).
To a solution of ethyl propiolate (2.73 mL, 27.0 mmol) in THF (50
mL) at –78 °C was slowly added n-BuLi (13 mL, 2.5 M in hexane,
32.4 mmol). After the mixture was stirred at –78 °C for 1 h, cyclo-
hexanone 18 (6.17 g, 27.0 mmol), dissolved in THF (5 mL), was
added dropwise. The reaction mixture was stirred for additional 2 h
at –78 °C and then allowed to warm to r.t. After another 1 h at r.t.,
the mixture was poured onto aq sat. NH4Cl (50 mL). After separa-
tion of the layers, the aqueous layer was extracted with Et2O (2 × 25
mL). The combined organic layers were dried with MgSO4, filtered,
and concentrated in vacuo. Purification of the residue by flash chro-
matography (Et2O–petroleum ether, 1:1) provided compound 28
(8.31 g, 94%) as a colorless, wax-like solid, mp 89.7–90.5 °C. TLC
(Et2O–petroleum ether, 4:1): Rf = 0.68. IR (KBr): 3413, 2954, 2857,
2230, 1714, 1472, 1369, 1254, 1057, 1019, 968, 848 cm–1. 1H NMR
(400 MHz, CDCl3): d = 0.01 [s, 6 H, Si(CH3)2], 0.85 [s, 9 H,
Si(CH3)3], 1.28 (t, J = 7.1 Hz, 3 H, CH2CH3), 1.65–1.70 [m, 4 H,
CH(CH2)2], 1.73–1.81 [m, 2 H, C(CHH)2], 1.96–2.05 [m, 2 H,
C(CHH)2], 2.39 (s, 1 H, OH), 3.80–3.86 (m, 1 H, CH), 4.20 (q,
J = 7.2 Hz, 2 H, CH2CH3). 13C NMR (400 MHz, CDCl3): d = –4.9
(C-9, C-15), 13.95 (C-20), 17.98 (C-16), 25.72 (C-17, C-21, C-22),
30.84 (C-2, C-6), 34.28 (C-3, C-5), 62.06 (C-19), 66.00 (C-4), 67.93
(C-1), 75.59 (C-12), 90.11 (C-11), 153.58 (C-13). MS (FAB): m/z
(%) = 349.1 (3) [M + Na]+, 327.1 (7) [M + H]+, 309 (28) [M + H –
H2O]+, 177 (95) [M + H – H2O – HOTBDMS]+, 105.1 (100) [M +
H – H2O – HOTBDMS – CO2Et]+. FT-ICR (ESI): m/z calcd for
C17H30O4SiNa: 349.18056; found: 349.18053.
b) From 28: MeOH (100 mL) was added to Na (1.44 g, 62.5 mmol)
under nitrogen atmosphere. After evolution of hydrogen was fin-
ished, the propynoic ester 28 (8.15 g, 25 mmol) was added and the
reaction was gently refluxed for 2 h. The mixture was poured onto
aq sat. NH4Cl (100 mL). After separation of the phases, the aqueous
layer was extracted with Et2O (2 × 40 mL). The combined organic
layers were dried with MgSO4 and the solvent was removed under
reduced pressure. The crude product was purified by flash chroma-
tography (Et2O–petroleum ether, 4:1) to yield compound 26 (5.02
g, 64%) as a colorless solid. TLC (Et2O–petroleum ether, 4:1):
Rf = 0.32. IR (KBr): 3113, 2935, 2888, 1759, 1635, 1446, 1365,
1241, 1057, 833, 463 cm–1. 1H NMR (400 MHz, CDCl3): d = 0.04
[s, 6 H, Si(CH3)2], 0.87 [s, 9 H, Si(CH3)3], 1.64–1.85 (m, 8 H, CH2),
3.57–3.66 [m, 1 H, (CH2)2CH], 3.85 (s, 3 H, OCH3), 4.95 (s, 1 H,
CH). 13C NMR (400 MHz, CDCl3): d = –4.60 (C-16, C-17), 18.09
(C-18), 25.80 (C-19, C-20, C-21), 31.12 (C-6, C-10), 31.72 (C-7, C-
9), 59.38 (C-13), 69.37 (C-8), 82.56 (C-5), 87.32 (C-3), 171.69 (C-
2), 185.69 (C-4). FT-ICR (ESI): m/z calcd for C16H28O4SiNa:
335.16491; found: 335.16526.
Further experimental details including copies of NMR spectra of
important compounds can be obtained from the author.
4,8-Dihydroxy-1-oxaspiro[4.5]dec-3-en-2-one (27).
The methyl tetronate 26 (6.25 g, 20 mmol) was added to HCl (5 N,
100 mL) and the mixture stirred for 5 h at 60 °C. The mixture was
diluted with H2O (100 mL), washed with n-hexane (50 mL) twice
and extracted with EtOAc (10 × 100 mL). The combined organic
layers were dried with NaSO4, filtered and concentrated in vacuo.
Purification of the residue by flash chromatography (EtOAc–petro-
leum ether, 4:1 + 0.1% HOAc) gave tetronic acid 27 (3.14 g, 85%)
as a colorless crystalline solid, mp 170.4–173.9 °C. TLC (EtOAc–
petroleum ether, 4:1 + 0.1% HOAc): Rf = 0.25. IR (KBr): 3251,
3132, 2938, 2862, 1893, 1732, 1678, 1620, 1304, 1053, 976, 802
cm–1. 1H NMR (400 MHz, DMSO): d = 1.33–1.57 [m, 4 H,
CH(CH2)2], 1.70–1.86 [m, 4 H, C(CH2)2], 3.36–3.49 [m, 1 H,
CH(CH2)2], 4.78 (s, 1 H, CH), 12.63 (s, 1 H, COH). 13C NMR (400
MHz, DMSO): d = 30.96 (C-6, C-10), 31.27 (C-7, C-9), 67.14 (C-
8), 81.82 (C-5), 86.50 (C-3), 172.07 (C-2), 185.01 (C-4). FT-ICR
(ESI): m/z calcd for C9H12O4Na: 207.06278; found: 207.06264.
Acknowledgment
Financial support by the Deutsche Forschungsgemeinschaft (grant
Ma 1012/17-1) and the Fonds der Chemischen Industrie is grate-
fully acknowledged. We also thank Prof. R. D. Süssmuth and the
members of his group for helpful discussions.
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LETTER
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Synlett 2005, No. 2, 314–318 © Thieme Stuttgart · New York