Towards a biomimetic synthesis of barrenazine A

Article abstract of DOI:10.1016/j.tetlet.2007.04.108

We report herein a concise and biomimetic synthesis of a precursor of barrenazine A, a cytotoxic alkaloid. The C₂-symmetry of this molecule suggested the dimerization of an aminoketone, as the precursor of the central core pyrazine. This compou

Full text of DOI:10.1016/j.tetlet.2007.04.108

Tetrahedron Letters 48 (2007) 4327–4330
Towards a biomimetic synthesis of barrenazine A
*
´ ´
´
Frederic Buron, Alain Turck, Nelly Ple, Laurent Bischoff and Francis Marsais
Laboratoire de Chimie Organique Fine et He´te´rocyclique (LCOFH), CNRS UMR 6014, Universite´ de Rouen—IRCOF,
INSA Rouen BP 08, 76131 Mont-Saint-Aignan Cedex, France
Received 21 March 2007; revised 18 April 2007; accepted 24 April 2007
Available online 27 April 2007
Abstract—We report herein a concise and biomimetic synthesis of a precursor of barrenazine A, a cytotoxic alkaloid. The C2-sym-
metry of this molecule suggested the dimerization of an aminoketone, as the precursor of the central core pyrazine. This compound
was prepared by assembly of aspartic acid and glycine.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
vated aspartic acid derivative. As depicted in Scheme
2, this synthetic pathway started with commercially
available N-Cbz aspartic acid a-benzyl ester (Z-Asp-
OBzl) (1). To effect the C-acylation of a glycine-derived
enolate, the free side-chain carboxylic acid was first acti-
vated with carbonyldiimidazole, but better results were
obtained when using an acid chloride. A smooth acyla-
tion of the enolate of ethyl N-diphenylmethylene glycin-
ate was obtained. The resulting a-imino-b-ketoester was
subsequently hydrolysed to yield the unstable hydro-
chloride 2. Unfortunately, this aminoketoester did not
lead to the expected pyrazine, but underwent a sponta-
neous cyclisation to afford lactam 3 in 85% overall yield,
predominantly observed as its enol tautomer.
In 20031 was reported the structural assignment of two
new cytotoxic alkaloids named barrenazines A and B,
extracted from a tunicate collected at Barren Islands,
Madagascar. These compounds display an interesting
symmetrical structure, consisting of a central pyrazine
ring, fused with two piperidines with a central C2-sym-
metry. More recently,2 an elegant synthesis involving a
diastereoselective addition of a Grignard reagent onto
a pyridinium salt was accomplished.
The presence of the pyrazine ring prompted us to syn-
thesize the central core of this molecule via condensation
of two identical aminoketones. Both stereogenic carbon
centres exhibiting the same stereochemistry revealed two
aspartic acid-derived synthons. Thus, we focused on a
retrosynthesis based on the dimerization of the amino-
ketone resulting from C-acylation of glycine by aspartic
acid side-chain carbonyl as shown in Scheme 1.
Presumably, this result may be explained by the low
reactivity of the ketone, due to its propensity for enoli-
zation. This low reactivity accounts for an easier intra-
molecular lactamisation, rather than the desired
intermolecular cyclic diimine formation.
The stereochemistry of the target molecule is consistent
with that of natural aspartic acid, suggesting a simple
transformation of the a-acid of the latter.
This result pointed out the need to lower the reactivity
of the a-acid. We initially believed that a reduction of
this acid moiety would afford an easy-to-handle alcohol
but spontaneous lactonisation of the latter prompted us
to introduce the alkyl chain in the first steps of the
synthesis.
2. Results and discussion
As shown in Scheme 3, reduction of the free a-acid of
commercially available Z-Asp(Ot-Bu)-OH with sodium
borohydride after chloroformate activation3 afforded the
alcohol 4. The optical purity of this alcohol was checked
by HPLC on chiral stationary phase and no racemisa-
tion was noticed. Mesylation of the latter was successful
but further attempt at reacting it with an homocuprate
Our first attempt at synthesizing this molecule consisted
in acylating a glycine equivalent with a suitably acti-
Keywords: Marine alkaloid; Barrenazine; Amino acid; Pyrazine
synthesis.
*
Corresponding author. Fax: +33 2 35522962; e-mail: laurent.bischoff@
insa-rouen.fr
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.04.108

4328
F. Buron et al. / Tetrahedron Letters 48 (2007) 4327–4330
N
(CH2)6CH3
NH
EtOOC
NH2
N
N
(CH2)6CH3
HN
H3C(H2C)6
NH2
COOEt
N
H3C(H2C)6
Barrenazine A
EtOOC
NH2
NH2
O
2 x
Asp + Gly
HOOC
Scheme 1. Retrosynthetic analysis of barrenazine A.
O
NHCbz
CbzHN
BnOOC
CbzHN
OH
a, b
COOH
COOEt
NH3+, Cl-
BnOOC
O
N
COOEt
H
1
2
3
Scheme 2. Reagents and conditions: (a) (COCl)2, cat DMF; (b) Ph2C@NCH2COOEt, t-BuOK, THF, ꢀ78 to 0 ꢁC, then H3O+.
NHZ
NHZ
NHZ
a
b
COOt-Bu
HO
COOt-Bu
RO2SO
COOt-Bu
HOOC
Z-Asp(Ot-Bu)-OH
4
5a : R= CH3
5b : R=4-Me(C6H4)
(5a)
Z
(5b)
d
N
c
COOt-Bu
6
(+ 4)
NHZ
NHZ O
O
NHZ O
O
f
e
C6H13
COOH
C6H13
C6H13
OEt
OEt
N
9
8
7
OH
g
C6H13
C6H13
O
NHZ O
O
EtOOC
NHZ
N
N
HN
C6H13
h
OEt
NHZ
COOEt
NH
N
NH2
N
O
C6H13
C6H13
10
11
Scheme 3. Reagents and conditions: (a) N-methyl morpholine, isobutyl chloroformate, ꢀ15 ꢁC, 1 min then aq NaBH4, 88%; (b) RSO2Cl, Et3N, cat
DMAP, CH2Cl2, 0 ꢁC, 54% (5a), 91% (5b); (c) (n-Hex)CuCNLi2, THF, ꢀ40 ꢁC, 26% (6); (d) (n-Hex)2CuLi, Et2O, ꢀ30 ꢁC, 70% then TFA, CH2Cl2,
rt, 100%; (e) Meldrum’s acid, DCC, DMAP, CH2Cl2, rt, then EtOH, reflux, 83%; (f) NaNO2, AcOH, rt, 98%; (g) Zn, AcOH, rt then Et3N, CH2Cl2,
air, rt; (h) H2, Pd/C, AcOH then toluene, reflux, 90%.
led to recovery of the starting alcohol, whereas the
cyanocuprate gave a mixture of alcohol 4 and aziridine
6. The necessary modulation of the leaving group reac-
tivity was obtained by replacing the mesylate with a tos-
ylate. Tosylation of the alcohol proceeded smoothly,
leading to 5b in 91% yield. Introduction of the alkyl
group was achieved via treatment with lithium dihexyl-
cuprate and subsequent TFA-mediated deprotection,
affording b-aminoacid 7.4 Interestingly, this aminoacid
was already found in another tunicate, and is a constit-
uent of the peptides Minalemines A and D.5 Further
formation of the pyrazine ring required the obtention
of an aminoketoester precursor. First experiments were
carried out by acylating diphenyliminoglycine ethyl
ester, but with this substrate the reaction was sluggish
and the yields were not reproducible. For these reasons
we decided to first prepare the b-keto ester before the
incorporation of the amino group.
Following this strategy, the acid was converted to the b-
ketoester 8 by acylation of Meldrum’s acid6 and reflux-
ing in ethanol. Introduction of the amino group was
carried out in a two-step electrophilic amination
procedure.7 Treatment of the b-ketoester with sodium
nitrite in acetic acid gave oxime 9 in a nearly quantita-
tive yield, as a mixture of (E) and (Z) isomers. Further
reduction with zinc in acetic acid converted the oxime
to the corresponding a-amino-b-ketoester which was
not isolated but underwent spontaneous dimerisation
followed by air-induced aromatization, to provide pyr-
azine 10. The last step was achieved by simultaneous
formation of both lactam rings. In this step, amine

F. Buron et al. / Tetrahedron Letters 48 (2007) 4327–4330
4329
deprotection by means of classical hydrogenolysis was
followed by rapid intramolecular amidification of ethyl
esters.
AcOH, 9:1:0.5) giving 3 (795 mg, 85%) as a yellow solid;
mp 155–156 ꢁC. H NMR (CDCl3): d 10.60 (br s, 1H),
1
7.34 (m, 5H), 5.86 (s, 1H), 5.11 (s, 2H), 4.32 (m, 3H),
3.21 (dd, J = 16.7, 6.6 Hz, 1H), 2.65 (m, 1H); 13C
NMR (CDCl3): d 165.8, 164.8, 157.5, 156.1, 136.1,
128.6, 104.3, 67.2, 62.1, 48.9, 32.4, 14.2; IR: 3311,
1659, 1529, 1239, 1073, 782, 746, 694 cmꢀ1. Anal. Calcd
for C16H18N2O6 (334.32): C, 57.48; H, 5.43; N, 8.38.
Found: C, 57.32; H, 5.19; N, 8.14.
Compound 11 was finally obtained in 29% yield over
eight steps. Unfortunately, attempts at reducing the
amide bonds were rendered difficult due to competitive
reduction of the pyrazine ring. This was observed with
hydrides such as NaBH4 or BH3, as well as with Raney-
nickel desulfurisation of the corresponding thioamide.
4.2.2.
3-(S)-3-Benzyloxycarbonylamino-4-hydroxy-1-
butanoic acid, t-butyl ester (4). To a solution of Z-Asp-
(Ot-Bu)-OH (2 g, 6.20 mmol) in 50 mL 1,2-dimethoxy-
ethane, was added N-methylmorpholine (0.47 mL,
6.51 mmol). The solution was stirred for 10 min at rt
and cooled to ꢀ15 ꢁC. Isobutyl chloroformate
(0.65 mL, 6.51 mmol) was added dropwise. After stirring
for 30 s at this temperature, N-methylmorpholine hydro-
chloride was removed by filtration through a short pad
of celite, washed with DME and the filtrate transferred
to a large flask chilled in an ice-salt bath. A solution
of NaBH4 (704 mg, 18.6 mmol) in 5 mL water was
added at once, producing a vigorous gas evolution. After
stirring for 1 h, 50 mL water was added and the alcohol
extracted with ethyl acetate. The crude product was puri-
fied by column chromatography (petroleum ether–
AcOEt, 1:1), yielding 4 (1.68 g, 88%), as a yellow liquid;
[a]20 ꢀ19.4 (c 1.1, CHCl3) (lit.8) [a]20 ꢀ19.6, (c 1.2,
3. Conclusion
This concise synthesis of an analogue of the natural
enantiomer of barrenazine A was achieved in eight steps
from suitably protected aspartic acid. Our retrosynthetic
analysis pointed out the assembly of a pair of Asp and
Gly, linked together with a carbon–carbon bond and
was validated by the easy formation of the pyrazine ring.
The natural alkaloid or some of its derivatives may be
accessible from diamide 11.
4. Experimental
4.1. General
1
Melting points were determined on a Kofler hot-stage
CHCl3); H NMR (CDCl3): d 7.33 (m, 5H), 5.60 (d,
1
apparatus. H spectra were recorded at 300 MHz and
J = 6.2 Hz, 1H), 5.10 (s, 2H), 4.30 (m, 1H), 3.67 (d,
J = 4.5 Hz, 1H), 2.53 (d, J = 6 Hz, 2H), 1.42 (s, 9H);
13C NMR (CDCl3): d 171.2, 156.4, 136.4, 128.6, 81.5,
66.9, 64.4, 50.4, 37.4, 28.1; IR: 3351, 2978, 1714, 1537,
1368, 1256, 1157, 1061, 698 cmꢀ1. Anal. Calcd for
C16H23NO5 (309.36): C, 62.12; H, 7.49; N, 4.53. Found:
C, 62.08; H, 7.59; N, 4.49.
13C NMR spectra at 75 MHz. IR spectra were obtained
from potassium bromide pellets. Anhydrous THF was
distilled from sodium/benzophenone. Unless otherwise
stated, column chromatographies were carried out
through silica gel (230–400 mesh)
4.2. Procedures and data
4.2.3. 3-(S)-3-(Benzyloxycarbonylamino)-p-toluene sulfon-
yloxy-butanoic acid t-butyl ester (5b). To a solution of
compound 3 (1.3 g, 4.20 mmol), triethylamine (0.89 mL,
6.30 mmol) and dimethylaminopyridine (51.3 mg,
0.42 mmol) in 60 mL CH2Cl2 under N2 at 0 ꢁC was
added a solution of tosyl chloride (1.20 g, 6.30 mmol)
in 5 mL CH2Cl2. The reaction medium was stirred for
12 h at 0 ꢁC and poured into ice-water. After extractive
work-up with ether, the crude product was purified by
column chromatography (heptane–ethyl acetate, 1:1).
Compound 5b crystallised upon trituration in petroleum
ether, as a white solid (1.77 g, 91%), mp 81–83 ꢁC. [a]20
ꢀ10.2 (c 1.1, CH2Cl2), lit.4 [a]20 ꢀ10.2 (c 3.1, acetone).
1H NMR (CDCl3): d 7.77 (d, J = 8.1 Hz, 2H), 7.34
(m, 7H), 5.35 (d, J = 8.6 Hz, 1H), 5.05 (s, 2H), 4.22
(m, 1H), 4.11 (d, J = 4.3 Hz, 2H), 2.53 (d, J = 5.9 Hz,
2H), 2.49 (s, 3H), 1.39 (s, 9H); 13C NMR (CDCl3): d
169.9, 155.5, 145.3, 136.3, 136.3, 128.4, 82.1, 70.2,
67.1, 47.1, 36.3, 28.1, 21.8; IR : 3369, 2971, 1658,
1524, 1023, 855, 698 cmꢀ1. Anal. Calcd for C23H29NO7S
(463.54): C, 59.59; H, 6.31; N, 3.02. Found: C, 60.14; H,
6.41; N, 3.01.
4.2.1.
(5S)-5-(Benzyloxycarbonylamino)-3-hydroxy-6-
oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid, ethyl
ester (3). A solution of N-benzyloxycarbonyl-aspartic
acid a-benzyl ester 1 (1 g, 2.80 mmol) and DMF
(100 lL) in 50 mL of dichloromethane was cooled to
0 ꢁC and treated with oxalyl chloride (0.53 mL,
4.19 mmol). The solution was stirred for 90 min at rt.
The solvent was removed in vacuo and the crude acid
chloride was dried under vacuum and used without fur-
ther purification. A solution of potassium tert-butoxide
(628 mg, 5.60 mmol) in 50 mL anhydrous THF was
cooled to ꢀ78 ꢁC under N2, and N-(diphenylmethyl-
ene)glycine methyl ester (1.50 g, 5.60 mmol) in 5 mL
THF was added. After 30 min, this orange solution
was added via cannula to a vigorously stirred solution
of the amino acid chloride in 50 mL dry THF at
ꢀ78 ꢁC. The mixture was stirred for 1 h, allowing the
temperature to reach 0 ꢁC. 50 mL of 3 M HCl were
added and stirring was kept for 1 h at rt. THF was
evaporated and the resultant aqueous layer washed with
ether, concentrated in vacuo, taken-up in water and
lyophilised. Methanol (20 mL) was added to the residue
and precipitated KCl was removed by filtration. Follow-
ing methanol evaporation, the crude product was puri-
fied by column chromatography (CHCl3–MeOH–
4.2.4. 3-(R)-3-Benzyloxycarbonylamino-decanoic acid
(7). A solution of 2.3 M n-hexyllithium in hexane
(19.7 mL, 45.3 mmol) was added dropwise at ꢀ20 ꢁC

4330
F. Buron et al. / Tetrahedron Letters 48 (2007) 4327–4330
over 20 min to a suspension of CuI (4.31 g, 22.6 mmol)
in dry ether under N2, turning from a yellow suspension
to a clear brown solution. After stirring for 25 min at
ꢀ20 ꢁC, then cooling down to ꢀ30 ꢁC, a solution of tos-
ylate 5b (3.5 g, 7.55 mmol) in 15 mL dry ether was added
over 20 min. The mixture was stirred at ꢀ30 ꢁC for 4.5 h
and treated with 50 mL satd NH4Cl and 10 mL concd
NH3. The brown organic layer was diluted with
100 mL ether and 20 mL AcOEt, and washed with brine
(3 · 25 mL). After drying and evaporation, the crude
product was taken-up in 15 mL dichloromethane and
trifluoroacetic acid (2 mL, 27 mmol) was added at rt.
After 5 h stirring, the solution was evaporated and the
residue was crystallised (petroleum ether–ether, 1:10)
to yield 7 (1.70 g, 70%), as a white solid, mp 107–
109 ꢁC; [a]20 +11.3 (c 1.67, CH2Cl2), lit.5 +10.0 (c
4.2.7. Diethyl 3(R),6(R)-3,6-di(benzyloxycarbonyl amino)-
pyrazine-2,5-dicarboxylate (10). To a solution of com-
pound 9 (600 mg, 1.47 mmol) in 10 mL acetic acid was
added zinc dust (965 mg, 14.7 mmol) in small portions.
The reaction mixture was stirred for 12 h at rt, then fil-
tered through a pad of celite, and the solid washed with
CH2Cl2. The solvents were evaporated, and the residue
dissolved in 20 mL dichloromethane. To this solution
was added triethylamine (0.62 mL, 4.44 mmol) and the
mixture was stirred for 1 h at rt. Additional water
(10 mL) was added, and the solution extracted with
dichloromethane (3 · 50 mL). The organic layer was
washed with brine (30 mL), dried over anhydrous
MgSO4 and the solvent evaporated. The crude product
was purified by column chromatography (petroleum
ether–AcOEt, 7:3), giving 10 (400 mg, 70%), as a white
1
1
0.48, CHCl3) H NMR (CDCl3): d 11.16 (m, 1H), 7.34
solid, mp 89–91 ꢁC. [a]20 ꢀ12.3 (c 1.54, CH2Cl2). H
(m, 5H,), 5.25 (d, J = 8.8 Hz, 1H), 5.10 (s, 2H), 3.96
(m, 1H), 2.60 (m, 2H), 1.53 (m, 2H), 1.25 (m, 10H),
0.88 (s, 3H); 13C NMR (CDCl3): d 177.3; 156.1; 136.4;
128.2; 66.9; 48.0; 38.9–22.7; 14.2; IR: 3331, 1952, 2923,
2853, 1692, 1537, 1258, 1064, 732, 695 cmꢀ1. Anal.
Calcd for C18H27NO4 (321.41): C, 67.26; H, 8.47; N,
4.36. Found: C, 67.11; H, 8.45; N, 4.39.
NMR (CDCl3): d 7.21 (m, 5H), 5.56 (d, J = 8.5 Hz,
1H), 4.92 (m, 2H), 4.32 (q, 2H), 4.02 (m, 1H), 3.25 (m,
2H),1.47 (m, 2H), 1.25 (m, 13H), 0.79 (s, 3H). 13C
NMR (CDCl3): d 165.0, 156.0, 152.0, 152.0, 136.9,
128.1, 66.5, 62.6, 51.4, 38.7–22.7, 14.2; IR: 3312, 2926,
2854, 1728, 1687, 1541, 1259, 1127, 697 cmꢀ1. Anal.
Calcd for C44H62N4O8 (774.46): C, 68.19; H, 8.06; N,
7.23. Found: C, 68.25; H, 8.07; N, 7.39.
4.2.5. Ethyl 5-(R)-5-(benzyloxycarbonylamino)-3-oxo-
dodecanoate (8). To a solution of compound 7 (3.3g,
10.2 mmol), Meldrum’s acid (1.62 g, 11.3 mmol) and
dimethylaminopyridine (0.375 g, 3.1 mmol) in 50 mL
CH2Cl2 was added N,N-dicyclohexylcarbodiimide
(2.32 g, 11.3 mmol). The solution was stirred for 12 h
at rt. N,N-dicyclohexylurea was filtered off and washed
with dichloromethane. The filtrate was washed with
5% HCl (25 mL), brine (30 mL), dried and concentrated.
The residue was refluxed in 100 mL absolute ethanol for
5 h. Following ethanol evaporation, the crude product
was purified by column chromatography (petroleum
ether–AcOEt, 7:3), providing 8 (3.33 g, 83%) as a white
4.2.8. (3R,8R)-3,8-Diheptyl-3,4,8,9-tetrahydrodipyrido
[4,3-b:40,30-e]pyrazine-1,6(2H,7H)-dione (11). To
a
solution of compound 10 (200 mg, 0.26 mmol) in
10 mL acetic acid was added 5% Pd/C (55 mg,
0.026 mmol). The mixture was stirred for 1 h at rt under
a hydrogen atmosphere and filtered. The precipitate was
washed with ethanol, and the solvents evaporated. The
solid was dissolved in toluene (15 mL), Et3N (0.08 mL,
0.52 mmol) was added and the solution was refluxed
for 2 h. After cooling, the solution was filtered to give
11 (48 mg, 90%) as a yellow solid. mp >250 ꢁC. [a]20
1
ꢀ50.8 (c 0.65, CHCl3); H NMR (CDCl3): d 6.54 (s,
1
solid, mp 83–85 ꢁC. [a]20 +10.5 (c 1.33, CH2Cl2). H
1H), 3.84 (m, 1H), 3.50 (dd, J = 16.6 and 4.8 Hz, 1H),
3.19 (dd, J = 16.6 and 4.8 Hz, 1H), 1.68 (m, 4H), 1.20
(m, 10H), 0.87 (m, 3H); 13C NMR (CDCl3): d 162.9,
153.6, 142.8, 50.4, 36.1–22.8, 14.2; IR: 3195, 3087,
NMR (CDCl3): d 7.36 (m, 5H), 5.09 (m, 3H), 4.21 (q,
2H), 3.96 (m, 1H), 3.46 (d, J = 6 Hz, 2H), 2.82 (m,
2H),1.53 (m, 2H), 1.28 (m, 13H), 0.89 (s, 3H); 13C
NMR (CDCl3): d 201.9, 167.1, 155.9, 136.2, 128.2,
66.8, 61.6, 49.9, 48.1, 47.2, 34.7–22.7, 14.2; IR: 3316,
2957, 2923, 2853, 1693, 1471, 1346, 1192, 807 cmꢀ1
.
Anal. Calcd for C24H38N4O2 (414.30): C, 69.53; H,
9.24; N, 13.51. Found: C, 69.47; H, 9.16; N, 13.44.
2959, 2922, 2854, 1736, 1712, 1681, 1542, 1269 cmꢀ1
.
Anal. Calcd for C22H33NO5 (391.50): C, 67.49; H,
8.50; N, 3.58. Found: C, 67.24; H, 8.67; N, 3.87.
References and notes
4.2.6. Ethyl 5(R)-2-(hydroxyimino)-5-(benzyloxy carbon-
ylamino)-3-oxododecanoate (9). To a solution of com-
pound 8 (500 mg, 1.27 mmol) in 10 mL acetic acid was
added dropwise an ice-cold solution of sodium nitrite
(0.45 g, 6.35 mmol) in 3 mL water. The mixture was stir-
red for 12 h, allowing the temperature to reach rt. Water
(10 mL) was added. Extractive work-up with ether affor-
1. Chill, L.; Aknin, M.; Kashman, Y. Org. Lett. 2003, 5, 2433.
2. Focken, T.; Charette, A. B. Org. Lett. 2006, 8, 2985.
3. Rodriguez, M.; Linares, M.; Doulut, S.; Heitz, A.; Marti-
nez, J. Tetrahedron Lett. 1991, 32, 923.
4. El Marini, A.; Roumestant, M. L.; Viallefont, P.; Razafindr-
amboa, D.; Bonato, M.;Follet, M. Synthesis 1992, 1104–1108.
5. Exposito, A.; Fernandez-Suarez, M.; Iglesias, T.; Munoz,
L.; Riguera, R. J. Org. Chem. 2001, 66, 4206.
6. Oikawa, Y.; Sugano, K.; Yonemitsu, O. J. Org. Chem.
1978, 43, 2087; Lokot, I. P.; Pashkovsky, F. S.; Lakhvich,
F. A. Tetrahedron 1999, 55, 4783.
7. Mordant, C.; Duenkelmann, P.; Ratovelomanana-Vidal,
V.; Genet, J.-P. Eur. J. Org. Chem. 2004, 3017.
1
ded 9 as a colourless liquid (523 mg, 98%). H NMR
(CDCl3): d 11.6( m, 1H), 7.34 (m, 5H), 5.49 (d,
J = 9.6 Hz, 1H), 5.05 (m, 2H), 4.38 (q, 2H), 3.96 (m,
1H), 3.16 (m, 2H),1.61 (m, 2H), 1.34 (m, 13H), 0.87 (s,
3H), 13C NMR (CDCl3): d 194.6, 162.1, 157.1, 136.4,
136.3, 128.5, 67.6, 62.6, 48.1, 41.9, 34.3, 23.0, 14.5; IR:
3375, 2928, 2856, 1693, 1530, 1455, 1259, 1026 cmꢀ1
.
8. Della Monache, G.; Misiti, D.; Salvatore, P.; Zappia, G.
Tetrahedron: Asymmetry 2000, 11, 1137.
MS (IC): m/z (%) = 439 (MNH4þ); 421 (MH+).