Synthesis of models of metabolites: Oxidation of variously substituted chromenes including acronycine, by a porphyrin catalytic system

Article abstract of DOI:10.1002/jhet.5570420704

The influence of chemical neighbouring on oxidation of substituted 2,2-dimethylchromenes derivatives 5-8 by a biomimetic catalytic system was first studied. It was then applied to acronycine an anti-cancer drug in order to obtain in one single step oxidized products resulting from the reactivity of the 1,2-double bond in the pyranic D-ring. These 2,2-dimethylchromenes constitute the structural moiety responsible for the activity of acronycine. This oxidation showed the sensitivity of the ethylenic bond, leading to the formation of the corresponding epoxides, diols and/or ketoalcohol. In the case of 5-dimethylamino-2,2-dimethylchromene 8, the double bond was not sensitive to oxidation, but the N-methyl groups reacted to lead to the formamide derivative 16 and an imino-alcohol 17. This methodology applied to acronycine molecule 1, allowed to obtain in one step, two oxidized compounds, a trans-diol 3 and a ketoalcohol 4 under preparative conditions.

Full text of DOI:10.1002/jhet.5570420704

Nov-Dec 2005
1267
Synthesis of Models of Metabolites: Oxidation of Variously Substituted
Chromenes Including Acronycine, by a Porphyrin Catalytic System
[a]
[a]
[a]
Bernardin Akagah , François Estour , Philippe Vérité ,
[a]
[b]
[a]
Elisabeth Seguin , François Tillequin , Olivier Lafont*
[a] Laboratoire de Pharmacochimie, Faculté de Médecine et de Pharmacie de Rouen,
22 Boulevard Gambetta, 76183 Rouen Cedex 1, France.
[b] Laboratoire de Pharmacognosie, U.M.R./C.N.R.S. No 8638,
Faculté des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l’Observatoire, 75006 Paris, France.
e-mail address : Olivier.Lafont@univ-rouen.fr
Received March 4, 2005
The influence of chemical neighbouring on oxidation of substituted 2,2-dimethylchromenes derivatives 5-
8 by a biomimetic catalytic system was first studied. It was then applied to acronycine an anti-cancer drug in
order to obtain in one single step oxidized products resulting from the reactivity of the 1,2-double bond in
the pyranic D-ring. These 2,2-dimethylchromenes constitute the structural moiety responsible for the activ-
ity of acronycine. This oxidation showed the sensitivity of the ethylenic bond, leading to the formation of the
corresponding epoxides, diols and/or ketoalcohol. In the case of 5-dimethylamino-2,2-dimethylchromene 8,
the double bond was not sensitive to oxidation, but the N-methyl groups reacted to lead to the formamide
derivative 16 and an imino-alcohol 17. This methodology applied to acronycine molecule 1, allowed to
obtain in one step, two oxidized compounds, a trans-diol 3 and a ketoalcohol 4 under preparative conditions.
J. Heterocyclic Chem., 42, 1267 (2005).
Metabolic studies in living animals can be limited by the
tives [8,9]. In particular, the trans-1,2-dihydroxy-1,2-dihy-
dro-acronycine (Figure 1, compound 3) isolated from
Sarmelicope glauca [10] proved to be a suitable candidate
for esterification reactions leading to active derivatives.
But, extraction yields of compounds from plants are
often weak. Microbiological methods did not allow one to
obtain any metabolites resulting from oxidation of the 1,2-
double bond [11]. Direct chemical oxidation of acronycine
by potassium permanganate [1] allowed for the prepara-
tion of the trans-diol of acronycine 3, but in two steps.
Direct oxidation led to a ketoalcohol 4, and had to be fol-
lowed by reduction of the keto function (Scheme 1) [1].
toxicity of a drug. Most often, it is not possible to adminis-
ter an anticancer drug during a long period, and alternative
methods are necessary to access models of metabolites. In
the particular case of acronycine (Figure 1, compound 1), a
natural alkaloid isolated from Acronychia baueri Schott, a
supplementary difficulty is caused by its very weak water-
solubility, which excludes parenteral formulation of the
drug [1]. Thus, only some experiments have been realized
in vivo [2]. Results of these biotransformations have
shown a reactivity of one of the methyl groups linked on
the D-ring or an hydroxylation on various positions of the
A-ring. Nevertheless, several studies proved that the 1,2-
double bond of the pyranic D-ring was the main structural
moiety of the molecule responsible for anticancer activity
[3-7].
Scheme 1.
Figure 1. Acronycine and its metabolites.
Recent published results allowed to consider acronycine
1,2-epoxide (Figure 1, compound 2) as the metabolite
which in vivo plays a major role in the anti-tumor activity
of acronycine [8]. Moreover, hydroxylated acronycine
analogs on the double bond have constituted excellent
chemical intermediates to access to more cytotoxic deriva-
Acronycine chemical oxidation by KMnO .
4
The original preparative chemical method using the bio-
mimetic catalytic system Mn(TDCPP)Cl [TDCPP stands

1268
B. Akagah, F. Estour, P. Vérité, E. Seguin, F. Tillequin, O. Lafont
Vol. 42
for tetrakis-(2,6-dichloro-phenyl)porphyrin]/imidazole/
H O had recently proved a great efficiency in the synthe-
diol 10 and an epoxide 9 with very weak yields (Scheme
2). Ths cis-epoxide 9 was stable enough to be isolated by
column chromatography without any transformation into
the corresponding diol.
2
2
sis of models of metabolites of bioactive compounds
(Figure 2) [12-14]. This approach allowed for example to
obtain, in a one-pot synthesis, sufficient amounts of sev-
eral oxidized products, in the case of octalones precursors
of steroids [14].
Scheme 2
2,2-Dimethylchromene oxidation.
No formation of epoxide was observed in the case of the
7-methoxy analog 6, but a keto alcohol 11 was isolated in
5% yield, in addition to the corresponding trans-diol 12
(Scheme 3).
III
Figure 2. Mn (TDCPP)Cl, imidazole, perhydrol.
Scheme 3
This novel method could then be applied to acronycine
in order to obtain, in one single step, oxidized products
resulting from the reactivity of the 1,2-double bond in the
pyranic D-ring. Before applying the method to the tetra-
cyclic alkaloid itself, it was necessary to study the influ-
ence of chemical neighbouring on the reactivity of this eth-
ylenic bond. Compounds 5-8 (Figure 3) constitute models
of the essential structural moiety responsible for
acronycine activity. Oxidation of these compounds by the
biomimetic manganese/porphyrin/imidazole catalytic sys-
tem, was then studied.
Scheme 3. 7-Methoxy-2,2-dimethylchromene oxidation.
Hypothesis was made that the ketoalcohol 11 resulted
from an oxidation at a higher degree from the correspond-
ing dihydroxy derivative (Scheme 4). In order to prove this
hypothesis, the diol 12 was submitted to a second reaction
catalyzed by the system Mn(TDCPP)Cl/imidazole/H O ,
2
2
under the same conditions as the first oxidation. This reac-
tion gave compound 11 in 40% yield. The hydroxy group
on C-4 in 12 underwent an additional oxidation leading to
a keto group conjugated with the phenyl.
Figure 3. Chromenes 5-8.
Scheme 4
Oxidation of 2,2-dimethylchromenes (5-8).
Oxidation of these substrates by the catalytic system
Mn(TDCPP)Cl/imidazole/H O occurred on the 3,4-dou-
2
2
ble bond (equivalent to 1,2-double bond in acronycine) for
compounds 5, 6 and 7. The sensitivity of this ethylenic
bond was slightly modified according to the nature and the
position of substituents on the 2,2-dimethylchromene syn-
thon. Compounds 5 and 6 showed a similar reactivity.
Unsubstituted dimethylchromene 5 gave mainly a trans-
3,4-Dihydroxy-7-methoxy-2,2-dimethylchromane oxidation.

Nov-Dec 2005
Synthesis of Models of Metabolites: Oxidation of Variously Substituted Chromenes
1269
Amongst the four chromenes, the 6-acetyl analog 7
proved to be the most reactive. Its oxidation led to the for-
mation of a trans-diol 13 together with two epoxides (cis-
epoxide 14 and trans-epoxide 15) in 31% total yield
(Scheme 5). Even if cis-epoxides were more common, the
formation of conformationally rigid systems such as trans-
epoxides had already been described in some cases [15,16].
cis-isomer) [19]. Moreover, the weak yield (2%) obtained
for the strained trans-epoxide 15 can be explained by its
instability during the chromatographic purification process.
This low stability was experimentally proved when a pure
sample of the trans-epoxide 15 was submitted to a second
chromatography on silica gel, a ring opening occured and it
led to a corresponding diol (in fact, it was the trans-diol 13).
Concerning the N,N-dimethyl-2,2-dimethylchromene 8,
the double bond was not sensitive to oxidation, but methyl
groups on the nitrogen atom reacted to lead to the for-
mamide derivative 16 and an imino-alcohol 17 resulting
from a dealkylation of 16 (Scheme 6). Carbon atoms in α
position of amino groups were sensitive to oxidation by
this catalytic manganoporphyrin system. This behaviour
had already been observed in the case of imidazole oxida-
tion, leading to carbonyl groups [12]. Furthermore, the
demethylation of N,N-dimethylamides often occured in
oxidation processes [20,21].
These results showed that the presence of a carbonyl
group in position 6 favoured the oxidation of the double
bond, while the presence of a nitrogen atom in position 5
lowered the sensitivity of the double bond to oxidation.
These two functions being both included in acronycine
formula it was interesting to study the relative influence of
both these functions on the behaviour of the double bond
in this alkaloid.
1
The epoxides 14 and 15 were characterized by H NMR
spectroscopy and mass spectrometry. In this experiment, the
formation of the trans-epoxide 15 was proved by compari-
son of spectral data to those of the cis 14. The mass spec-
+_
trum showed a molecular peak at M = 218 for both iso-
mers. The original Karplus equation [16,17] is not applica-
ble in the case of rigid compounds. Anyway, in such confor-
mationally restricted systems, a specific Karplus-like rela-
tionship exists between the dihedral angle and the corre-
sponding vicinal proton – proton coupling constant [18].
The vicinal coupling constant between H-3 (3.5 ppm) and
H-4 (3.9 ppm) is 4.2 Hz for compound 14, while it is 8.9 Hz
for compound 15. The high coupling constant between H-3
and H-4 is only in agreement with a trans stereochemistry.
13
The difference between C NMR chemical shifts ∆δ for C-
3 and C-4 was 11.8 ppm for cis-epoxide 14, and 16.4 ppm
for trans-epoxide 15. This observation is in agreement with
what was observed for trans and cis-10-methyldecalin
epoxides (∆δ = 16.8 ppm for trans and ∆δ = 12.1 ppm for
Scheme 5
6-Acetyl-2,2-dimethylchromane oxidation.
Scheme 6
N,N-Dimethyl-2,2-dimethylchromene oxidation.

1270
B. Akagah, F. Estour, P. Vérité, E. Seguin, F. Tillequin, O. Lafont
Vol. 42
NMR (75 MHz) spectra were taken on a Brüker Avance DPX spec-
Oxidation of Acronycine (1).
1
13
trometer. H NMR and C NMR spectra were obtained in CDCl
3
Oxidation of this anticancer agent presented two major
interests. The first was to compare the sensitivity of the
different positions, which could potentially be oxidized to
more functionalized chemical structures. The second
advantage of this approach was to prepare models of
metabolites from acronycine.
Oxidation of acronycine by hydrogen peroxide cat-
alyzed by Mn(TDCPP)Cl in the presence of imidazole
(same conditions as previuos oxidations) led to two oxi-
dized products, the trans-diol 3 and the ketoalcohol 4
(Scheme 7). In both cases, the ethylenic bond proved to be
the most reactive part of the molecule despite the presence
of an aminomethyl group. In opposition to what occured in
open systems, the aminomethyl group when it was
included in a quinolone ring, was not able to protect the
double bond from oxidation. On the other hand, the pres-
ence of a carbonyl in position β to the nitrogen atom acti-
vated the double bond as it was the case for compound 7.
Oxidation of the ethylenic bond occurred in acronycine as
it had already been the case for chromenes 5 – 7.
with tetramethysilane as an internal standard. Mass spectra were
obtained on a GC-MS system. An Agilent 6890 gas chromatograph
was equipped with a non polar capillary column; the carrier gas was
helium. The mass spectrometer (Hewlett Packard 5970 MSD) was
operating in electron impact mode (70 eV) and directly interfaced
with the gas chromatograph apparatus.
Mn(TDCPP)Cl was prepared according to published procedures
[22-25]. The 2,2-dimethylchromenes (5-7) and acronycine (1)
were prepared according to the method previously described [6].
5-Dimethylamino-2,2-dimethylchromene (8).
To a solution of 5-amino-2,2-dimethylchromene [6] (1.05 g, 6
mmoles) in dry THF (10 ml) was added sodium hydride (0.72 g,
18 moles, 60% dispersion in oil). The mixture was stirred for
thirty minutes, methyl iodide (1.2 ml, 18 mmoles) was added,
and the reaction mixture was refluxed for eleven hours, sodium
hydride (0.36 g, 9 mmoles) and sodium iodide (0.6 ml, 9 mmoles)
were then added. The reaction mixture was refluxed for 48 addi-
tional h. The solvent was evaporated under reduced pressure. The
residue was dissolved in 15 ml of ammonium chloride, then
extracted with 4 x 15 ml of ethyl acetate. The organic layers were
collected and dried over sodium sulfate. The solvent was
Scheme 7
Acronycine oxidation by Mn(TDCPP)Cl.
removed in vacuo. The crude product was purified via chro-
matography (solid phase: SiO , solvent: CH Cl ). Compound 8
Nevertheless, no epoxide was isolated, probably due to the
very low stability of such a structure included in a bulky
system as acronycine.
2
2
2
-1
1
was obtained in 95% yield; ir: 3215, 2975 cm ; H nmr: δ 1.22
(s, 6H, 2 x CH ) ; 2.52 (s, 6H, 2x CH ), 5.38 (d, 1H, H-3, J = 9.8
3
3
Direct acronycine oxidation in these two oxidized com-
pounds constituted an interesting result, because the other
chemical method, using potassium permanganate had only
given the ketoalcohol 4. The obtention of 3 needing then
either another chemical step (reduction) or an extraction
from Sarcomelicope glauca. Thus, the use of Mn(TDCPP)Cl
proved to be an essential tool to obtain in one single step suf-
ficient amounts of oxidized products from acronycine, and it
allowed to synthesize major chemical intermediates for the
development of the structure-activity relationships in the
acronycine series.
Hz), 6.27-6.33 (m, 2H, 6-H and H-8), 6.40 (d, 1H, H-4, J = 9.8
13
Hz), 6.83 (t, 1H, H-7, J = 8.0 Hz); C nmr: δ 27.7 (C -CH ),
2
3
45.0 (N-CH ), 75.1 (C-2), 110.0 (C-8), 110.9 (C-6), 115.0 (C-4a),
3
120.4 (C-4), 128.5 (C-3), 129.2 (C-7), 151.2 (C-5), 154.4 (C-8a);
+•
ms: m/z 203 (M , 53), 189 (22), 188 (100), 173 (17), 172 (24),
160 (12), 144 (9), 93 (15).
Anal. Calcd. for C
H NO: C, 76.86; H, 8.36; N, 6.89.
13 17
Found: C, 76.58; H, 8.61; N, 7.02.
General Procedure for Oxidation of Acronycine 1 and Substrates
5-8.
A solution of Mn(TDCPP)Cl (0.25 mmol), imidazole (1
mmole) and substrate (10 mmoles) in 33 ml of dichloromethane/
acetonitrile (1/1, v/v) was prepared in a flask. In another flask,
imidazole (5 mmoles) was dissolved in 45 ml of acetonitrile, then
hydrogen peroxide (35% in water, 5 ml) was added. This mixture
was added dropwise (during two hours) at room temperature to
the first solution. The mixture was stirred at room temperature for
EXPERIMENTAL
Melting points were determined on a Kofler hot-plate melting
1
13
point apparatus and are not corrected. H NMR (300 MHz) and
C

Nov-Dec 2005
Synthesis of Models of Metabolites: Oxidation of Variously Substituted Chromenes
1271
two more hours. The solvent was then evaporated under reduced
pressure, and the residual oil was chromatographed (solid phase:
silica gel, solvent: dry acetone) in order to separate the products
from the catalyst. A second chromatography (solid phase: silica
gel; solvent: see below) was necessary to separate the different
oxidized products of the reaction.
(C-2), 118.4 (C-8), 120.2 (C-4a), 130.0 (C-7), 130.9 (C-6), 131.6
(C-5), 157.4 (C-8a), 196.9 (C=O). ms: m/z 218 (M , 48), 203
(12), 187 (42), 175 (100), 162 (32), 147 (42).
+•
Anal. Calcd. for C
H O : C, 71.58; H, 6.41. Found: C,
13 14 4
71.23; H, 6.18.
Trans-3,4-Epoxy-6-acetyl-2,2-dimethylchromane (15).
Oxidation of acronycine 1.
This compound was obtained in 2% yield; mp 109-111°; ir:
-1 1
The solvent for the second chromatography was cyclo-
hexane/dry acetone (1/1, v/v). Both isolated compounds 3 (yield:
15%) and 4 (yield: 9%) were already known compounds[1,10].
3050, 2935, 1385, 1270 cm ; H nmr: δ 1.19 (s, 3H, CH ), 1.49
3
(s, 3H, CH ), 2.50 (s, 3H, CH CO), 3.79 (d, 1H, H-3, J = 8.9 Hz),
3
3
4.92 (d, 1H, H-4, J = 8.9 Hz), 6.77 (d, 1H, H-8, J = 8.3 Hz), 7.74
13
(d, 1H, H-7, J = 8.3 Hz), 8.06 (s, 1H, H-5); C nmr: δ 19.2
Oxidation of 2,2-Dimethylchromene 5.
(CH ), 27.0 (CH ), 27.2 (CH CO), 60.1 (C-4), 76.5 (C-3), 80.1
3a
3b
3
The solvent for the second chromatography was cyclo-
hexane/ethyl acetate (1/2, v/v). Both isolated compounds 3,4-
epoxy-2,2-dimethyl-chromane 9 (yield: 2%) and 3,4-dihydroxy-
2,2-dimethylchromane 10 (yield: 15%) were already known
compounds [26-30].
(C-2), 117.8 (C-8), 120.9 (C-4a), 130.7 (C-7), 131.0 (C-6), 131.7
(C-5), 156.8 (C-8a), 197.1 (C=O); ms: m/z 218 (M , 25), 203
(3), 190 (9), 176 (12), 175 (100).
+•
Anal. Calcd. for C H O : C, 71.58; H, 6.41. Found: C,71.10;
13 14
3
H, 6.15.
Oxidation of 7-Methoxy-2,2-dimethylchromene 6.
Oxidation of 5-Dimethylamino-2,2-dimethylchromene 8.
The solvent for the second chromatography was cyclohexane/
ethyl acetate (1/1, v/v). 3,4-Dihydroxy-7-methoxy-2,2-dimethyl-
chromane 12 (yield: 13%) was a known compound [30-32].
The solvent for the second chromatography was cyclo-
hexane/ethyl acetate (1/1, v/v).
5-N-Methylformamido-2,2-dimethylchromene (16).
3-Hydroxy-7-méthoxy-2,2-dimethylchroman-4-one (11).
This compound was obtained in 11.5% yield; ir: 3000, 1690,
This compound was obtained in 5% yield; ir: 3450, 2920,
-1 1
1620, 1490 cm ; H nmr: δ 1.38 (s, 6H, 2 x CH ), 3.15 (s, 3H, N-
3
-1 1
1660, 1585 cm ; H nmr: δ 1.18 (s, 3H, CH ), 1.56 (s, 3H, CH ),
3
3
CH ), 5.64 (d, 1H, H-3, J = 10.0 Hz), 6.21 (d, 1H, H-4, J = 10.0
3
3.72 (d, 1H, OH, J = 2.2 Hz), 3.76 (s, 3H, OCH ), 4.28 (d, 1H, H-
3
Hz), 6.61 (d, 1H, H-6, J = 8.0 Hz), 6.73 (d, 1H, H-8, J = 8.0 Hz),
3, J = 2.2 Hz), 6.31 (d, 1H, H-8, J= 2.0 Hz), 6.50 (dd, 1H, H-6, J
13
7,05 (t, 1H, H-7, J = 8.0 Hz), 8.08 (s, 1H, CHO); C nmr: δ 28.1
13
= 2.0, 9.0 Hz), 7,68 (d, 1H, H-5, J = 9.0 Hz); C nmr: δ 19.7
(C -CH ), 34.2 (N-CH ), 76.4 (C-2), 116.7 (C-8), 117.5 (C-4),
2
3
3
(CH ), 27.3 (CH ), 56.3 (OCH ), 76.2 (C-3), 82.1 (C-2), 101.7
3
3
3
118.7 (C-4a), 129.4 (C-6), 129.7 (C-7), 132.4 (C-3), 138.4 (C-5),
(C-6), 110.3 (C-8), 112.6 (C-4a), 128.8 (C-5), 162.3 (C-8a),
+•
154.5 (C-8a), 163.7 (C=O); ms: m/z 217 (M , 17), 203 (16), 202
+•
167.3 (C-7), 193.0 (C-4); ms: m/z 222 (M , 34), 193 (20), 178
(100), 161 (41), 87 (9).
(5), 152 (12), 151 (100).
Anal. Calcd. for C
H NO : C, 71.91; H, 6.90; N, 6.44.
13 15 2
Anal. Calcd. for C
H O : C, 64.89; H, 6.30. Found: C,
12 14 4
Found: C, 71.73; H, 7.10; N, 6.31.
64.72; H, 6.69.
5-Formamido-2,2-dimethylchromene (17) (5-N-Hydroxyform-
imino-2,2-dimethylchromene).
Oxidation of 6-Acetyl-2,2-dimethylchromene 7.
The solvent for the second chromatography was cyclo-
hexane/ethyl acetate (7/3, v/v).
This compound was obtained in 3% yield; ir: 3350, 3050,
-1 1
1690, 1580 cm ; H nmr: δ 1.18 (s, 3H, CH ), 1.37 (s, 3H, CH ),
3
3
5.66 (d, 1H, H-3, J = 10.0 Hz), 6.31 (d, 1H, H-4, J = 10.0 Hz),
3,4-Dihydroxy-6-acetyl-2,2-dimethylchromane (13).
6.58-6.66 (m, 2H, H-6, H-8), 7.03 (t, 1H, H-7, J = 8.0 Hz), 8.14
This compound was obtained in 21% yield; mp 129-131°; ir:
13
(d, 1H, OH, J = 8.2 Hz), 8.37 (d, 1H, N=CH, J = 8.2 Hz);
C
-1
1
3450, 3050, 2980, 1614 cm ; H nmr: δ 1.17 (s, 3H, CH ), 1.40
3
nmr: δ 30.7 (C -CH ), 76.2 (C-2), 115.1 (C-8), 116.8 (C-4),
125.9 (C-4a), 127.1 (C-6), 129.7 (C-7), 132.4 (C-3), 136.1 (C-5),
154.3 (C-8a), 164.3 (N=CH-OH); ms: m/z 204 ((M+H) , 14),
2
3
(s, 3H, CH ), 2.40(s, 3H, CH CO), 3.51 (d, 1H, H-3, J = 8.9 Hz),
3
3
4.50 (d, 1H, H-4, J = 8.9 Hz), 4.60 (s broad, 1H, OH), 5.00 (s
broad 1H, OH), 6.65 (d, 1H, H-8, J = 8.7 Hz), 7.63 (d, 1H, H-7, J
+
189 (13), 188 (100), 160 (21).
13
= 8.7 Hz), 8.00 (s, 1H, H-5); C nmr: δ 19.5 (CH ), 26.9 (CH ),
3
3
Anal. Calcd. for C
H NO : C, 70.96; H, 6.40; N, 6.89.
12 13 2
27.0 (CH CO), 69.2 (C-4), 75.8 (C-3), 80.2 (C-2), 117.2 (C-8),
3
Found: C, 70.61; H, 6.08; N, 7.13.
124.1 (C-4a), 129.3 (C-6), 130.2 (C-7), 130.2 (C-5), 157.2 (C-
+•
8a), 198.3 (C=O); ms: m/z 236 (M , 39), 218 (11), 187 (89), 175
Acknowledgement.
(38), 165 100), 163 (27), 149 (53), 72 (34).
The authors thank Emilie Toussaint for excellent technical
assistance.
Anal. Calcd. for C
H O : C, 66.12; H, 6.77. Found: C,
13 16 4
65.81; H, 6.57.
Cis-3,4-Epoxy-6-acetyl-2,2-dimethylchromane (14).
REFERENCES AND NOTES
This compound was obtained in 8% yield; mp 119-121°; ir:
-1
1
3050, 2935, 1385, 1270 cm ; H nmr: δ 1.22 (s, 3H, CH ), 1.53
3
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3
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13
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(CH ), 25.9 (CH ), 26.7 (CH CO), 51.0 (C-4), 62.8 (C-3), 74.7
3
3
3

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Vol. 42
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