Chemotherapy of leishmaniasis Part VI: Synthesis and bioevaluation of some novel terpenyl S,N- and N,N-acetals

Article abstract of DOI:10.1016/j.ejmech.2006.09.016

Some novel terpene based oxoketene S,N-acetals 2(a-g) and N,N-acetals 3(a-c) have been synthesized from oxoketene dithioacetal 1. The compounds were screened for their in vivo antileishmanial activity. Some of the compounds showed 50-70% inhibition in the

Full text of DOI:10.1016/j.ejmech.2006.09.016

European Journal of Medicinal Chemistry 42 (2007) 511e516
http://www.elsevier.com/locate/ejmech
Short communication
Chemotherapy of leishmaniasis Part VI: Synthesis and bioevaluation of
some novel terpenyl S,N- and N,N-acetals*
a
a
a
b
S.N. Suryawanshi a, , Susmita Pandey , Rashmirathi , B.A. Bhatt , Suman Gupta
*
a Division of Medicinal Chemistry, Central Drug Research Institute, Chatter Manzil, Lucknow 226001, Uttar Pradesh, India
b Division of Parasitology, Central Drug Research Institute, Chatter Manzil, Lucknow 226001, Uttar Pradesh, India
Received 18 April 2006; received in revised form 16 September 2006; accepted 21 September 2006
Available online 18 December 2006
Abstract
Some novel terpene based oxoketene S,N-acetals 2(aeg) and N,N-acetals 3(aec) have been synthesized from oxoketene dithioacetal 1. The
compounds were screened for their in vivo antileishmanial activity. Some of the compounds showed 50e70% inhibition in the hamster model.
Ó 2006 Elsevier Masson SAS. All rights reserved.
Keywords: Ionones; Oxoketene S,N- and N,N-acetals; Antileishmanial activity
1. Introduction
molecules [10] and some novel terpenyl 2,4-diamino pyrimi-
dines [11] are showing promising antimicrobial and dihydro-
folate reductase inhibitory activities. Rationally designed
2,4-diamino pyrimidines [12] and some computer aided mole-
cules [13] are also giving further inputs in the leishmanial di-
hydrofolate reductase activity. In continuation of our studies
on terpenyl pyrimidines as novel antileishmanial agents [14],
we synthesized some novel terpenyl S,N-acetals and N,N-ace-
tals, and evaluated them for their in vivo antileishmanial activ-
ity and the results are reported in this communication.
Leishmaniasis is an infection caused by protozoa of the
genus Leishmania presenting several forms of the disease
such as cutaneous (CL), mucocutaneous (MCL) and visceral
leishmaniasis (VL), which can be fatal when untreated. The
chemotherapy currently available for leishmaniasis is far
from satisfactory. Resistance to the pentavalent antimonials
[1,2], which have been recommended drugs for the treatment
of both visceral (VL) and cutaneous leishmaniasis (CL) for
>50 years, is now widespread in India. Although new drugs
have become available in recent years for the treatment of
VL including amphotericin B lipid complex [3] and the oral
drug miltefosine [4], treatment problems remain. Currently, ef-
forts are being made to search for new molecules from natural
sources and in this endeavour diaryl heptanoids [5,6,7],
oxygenated abietanes [8], iridoids [9] and heterocyclic ion-
one-like molecules [10] are showing promise as new lead
molecules. Randomly designed heterocyclic ionone-like
2. Chemistry
The polarized ketene dithioacetals, the masked a-ketoacids
are a novel class of compounds having considerable potential
in synthetic organic chemistry [15]. However, their biological
potential has not been fully explored. They are easily prepared
by reacting the corresponding active methylene compounds
with carbon disulfide in the presence of a suitable base fol-
lowed by alkylation, often in a one pot reaction [16]. Many
experimental variations have been developed within this broad
procedural framework to suit the substrate characteristics such
as the acidities of active methylene hydrogens, specific base
*
CDRI communication no. 6262.
* Corresponding author.
E-mail address: shivajins@yahoo.co.in (S.N. Suryawanshi).
0223-5234/$ - see front matter Ó 2006 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2006.09.016

512
S.N. Suryawanshi et al. / European Journal of Medicinal Chemistry 42 (2007) 511e516
sensitive functional groups and the optimum yields of the
corresponding dithioacetals.
in 42% yield. Similarly, m-fluoroaniline furnished 2e in 30%
yield. Cyclohexylamine, comparatively more reactive than ar-
ylamines, reacted with 1 in ethanol (reflux, 20 h) and furnished
2f in 43% yield as a white crystalline solid, which melted at
75e76 ꢀC.
The terpenyl ketene dithioacetal 1 was synthesized using
our recently developed method [17]. The literature methods
used in the synthesis of S,N- and N,N-acetals proved less use-
ful for the synthesis of terpenyl S,N- and N,N-acetals.
The reaction of b-ionone ketene dithioacetal 1 with aniline
at ethanol reflux temperature was found to be very slow and it
did not provide S,N- or N,N-acetal. However, the reaction of 1
with aniline in ethanol under steel bomb conditions (Table 1,
entry-1) furnished 2a in 59% yield. The reaction of p-methox-
yaniline with 1 was more facile as expected (Table 1, entry-2)
and it furnished S,N-acetal 2b in quantitative yield. The
method was found to be general and it worked on a series of
amines (Table 1). Chloroaniline was found to be less reactive
and did not react with 1 at ethanol reflux temperature. How-
ever, it reacted with 1 under steel bomb conditions (Table 1,
entry-3) to furnish S,N-acetal 2c as a crystalline compound
which melted at 85e86 ꢀC. The 1H NMR spectrum of 2c
was in agreement with the assigned structure. Under identical
reaction conditions p-fluoroaniline reacted with 1 to furnish 2d
Having successfully synthesized S,N-acetals of aryl/alkyl-
amines we turned our attention towards secondary amines.
The reaction of N-ethylaniline with 1 (Table 1, entry-7)
furnished S,N-acetal 2g in 60% isolated yield. The reaction
of excess of morpholine with 1 was quite facile and it
furnished N,N-acetal 3b in 68% yield as a colourless crystal-
line solid which melted at 141e142 ꢀC. The 1H NMR
spectrum of 3b displayed a doublet at 7.20 ppm (J ¼
16.00 Hz) for H-5 proton, another doublet at 6.10 ppm
(J ¼ 16.00 Hz) for H-4 proton, a singlet at 4.60 ppm for
the H-2 proton, and it confirmed the assigned structure.
Similarly, the reaction of 1 with piperazine was equally fac-
ile (ethanol reflux, 5 h) to furnish N,N-acetal 3a in quantita-
tive yield. The reaction of 1 with 1,2-diaminoethane was
quite facile and it furnished cyclic N,N-acetal 3c in 60%
yield (Table 1, entry-10).
i)
SMe
SMe
O
SMe
R
O
1
2
F
a) R
b) R
=
=
N
H
e) R =
f) R =
N
H
N
H
OMe
N
H
i)
c) R =
N
H
Cl
F
g) R
=
N
d) R
=
N
H
R1
R2
O
H
N
3
HN
O
a) R1 = R2
=
N
N
NH
O
3c
b) R1 = R2
=
Reaction conditions: 1) Amine, ethanol, steel bomb, heat.

S.N. Suryawanshi et al. / European Journal of Medicinal Chemistry 42 (2007) 511e516
513
Table 1
Serial
no.
Substrate
Amine
Reaction conditions
Product
S,N-acetal, %
N,N-acetal, %
H2N
1
1
Steel bomb, EtOH, 100e110 ꢀC, 9 h
2a, 59
e
H2N
H2N
H2N
OMe
Cl
2
3
4
5
6
7
8
1
1
1
1
1
1
1
EtOH, reflux, 15 h
2b, 87
2c, 90
2d, 42
2e, 30
2f, 43
2g, 68
e
e
Steel bomb, EtOH, 100e120 ꢀC, 20 h
Steel bomb, EtOH, 100e120 ꢀC, 22 h
EtOH, reflux, 40 h
e
F
e
F
H2N
H2N
e
EtOH, reflux, 20 h
e
HN
HN
EtOH, reflux, 20 h
e
NH
O
EtOH, reflux, 5 h
3a, 81
HN
9
1
1
EtOH, reflux, 5 h
EtOH, reflux, 5 h
e
e
3b, 60
3c, 60
NH2
NH2
10
3. Biological activities
P.I. ¼ percent inhibition of amastigotes multiplication,
ANAT ¼actual number of amastigotes in treated animals,
INAT ¼ initial number of amastigotes in treated animals, and
TIUC ¼ times increase of parasites in untreated control
animals.
The in vivo leishmanicidal activity was determined in golden
hamsters (Mesocricetus auretus) infected with HOM/IN/80/
DD8 strain of Leishmania donovani obtained through the cour-
tesy of P.C.C. Garnham, Imperial College, London (U.K.).
For in vivo evaluation of compounds, the method of Bever-
idge [18] as modified by Bhatnagar et al. [19] and Gupta et al.
[20] was employed. Male hamsters weighing 35e40 g were
infected with 1 ꢁ 107 amastigotes and the intensity of infec-
tion after 20 days was assessed by spleen biopsy. Animals
with 2þ infections (5e15 amastigote/100 cell nuclei) were se-
lected for screening the compounds. The infected animals
were randomized into several groups on the basis of their par-
asitic burdens. Usually 4e6 animals were used for each com-
pound and the same numbers were kept as untreated controls.
The drug treatment was given intraperitoneally for five con-
secutive days at 50 mg/kg dose level (Table 2). To assess the
effect of test compounds spleen biopsies were performed on
each animal after 7 and 28 days of last drug administration
and amastigote counts were assessed by Giemsa staining.
The percentage inhibition in amastigote multiplication was
calculated using the following formula:
4. Results and discussion
In our earlier studies [21] we have shown a-oxoketene di-
thioacetals as good pharmacophores in the chemotherapy of
Table 2
Antileishmanial activity of compounds against L. donovani in hamsters
Serial no.
Compound no.
Dose, mg/kg
Day-7, %
inhibition
Day-28, %
inhibition
1
2a
2b
50
50
50
50
50
50
50
50
50
50
50
40
12.5
NI (i.p.)
52 (i.p.)
18 (i.p.)
31 (i.p.)
53 (i.p.)
46 (i.p.)
NI (i.p.)
All died
NI
ND
ND
2
3
2c
2d
ND
ND
4
5
2e
ND
ND
6
2f
2g
7
ND
ND
8
3a
3b
9
10
ND
3c
3c
30 (i.p.)
40 (oral)
93 (i.p.)
94 (oral)
65 (IP)
71 (oral)
75 (i.p.)
69 (oral)
11
12
Stibanate
Miltefosine
ANAT ꢁ 100
P:I: ¼ 100 ꢂ
INAT ꢁ TIUC

514
S.N. Suryawanshi et al. / European Journal of Medicinal Chemistry 42 (2007) 511e516
leishmaniasis. We visualized that the activity profile of these
compounds was probably due to their alkylating nature i.e.
DNA alkylation properties. In the present study we visualized
that S,N-acetals and N,N-acetals probably may not be good al-
kylating agents but they can be good metal chelates and the
property is very much useful in the chemotherapy of cancer
and leishmania [22a,b]. As we expected S,N-acetals 2b and
2e showed 50e53% in vivo antileishmanial profile on day-7.
However, S,N-acetals having p-chloro and p-fluoro substitu-
tions resulted in the diminition of biological activity. However,
N,N-acetal 3c was found more interesting. It did not show in-
hibition on day-7 but on day-28 it showed 65% activity by in-
traperitoneal route. By oral route it was found better on day-28
and it showed 71% activity. In view to access their full biolog-
ical potential further optimization studies are in progress.
J ¼ 10.00 Hz, 2H), 7.15 (d, J ¼ 10.00 Hz, 1H), 7.35 (d,
J ¼ 16.00 Hz, 1H); 13C NMR (200 MHz) d 14.827 (q),
19.467 (t), 22.137 (q), 2 ꢁ 29.257 (q), 33.778 (s), 34.528 (t),
40.154 (t), 55.682 (q), 92.742 (d), 2 ꢁ 114.495 (d),
2 ꢁ 127.166 (d), 131.443 (s), 132.505 (d), 133.608 (s),
136.884 (s), 138.170 (d), 158.469 (s), 168.269 (s), 184.050
(s); MS: m/e 372 (mþ þ 1). Anal. calcd. for C22H29NO2S: C,
71.17; H, 7.87; N, 3.77. Found C, 70.98; H, 7.67; N, 3.79.
5.3. 1-Thiomethyl-1-N-( p-chlorophenyl amino)-5-
(20,60,60-trimethyl)-cyclohex-20-en-10-yl-pent-1,4-dien-3-
one (2c)
M.p. 85e86 ꢀC; IR (KBr, cmꢂ1) 3390, 2925, 1598; 1H
NMR (CDCl3, 200 MHz) d 1.00 (s, 6H), 1.40 (m, 2H), 1.60
(m, 2H), 1.75 (s, 3H), 2.00 (m, 2H), 2.30 (s, 3H), 5.20 (s,
1H), 6.05 (d, J ¼ 16.00 Hz, 1H), 7.25 (m, 5H); 13C NMR
(200 MHz) d 15.043 (q), 19.474 (t), 22.180 (q), 2 ꢁ 29.295
(q), 33.886 (t), 34.613 (t), 40.226 (t), 93.975 (d), 126.416
(d), 2 ꢁ 129.518, (d) 2 ꢁ 131.872 (d), 132.663 (s), 133.784
(s), 134.251 (s), 137.136 (s), 137.585 (s), 139.066 (d),
166.848 (s), 184.578 (s); MS: m/e 376 (mþ þ 1). Anal. calcd.
for C21H26OSClN: C, 67.10; H, 6.97; N, 3.73. Found: C,
66.68; H, 7.36; N, 4.06.
5. Experimental
The reported melting points (ꢀC) are the uncorrected ones.
The infrared spectra were recorded in KBr on a Perkin Elmer
model 881. NMR spectra were obtained in CDCl3 (with Me4Si
internal standard, Aldrich) and are reported in ppm downfield
from Me4Si. Proton, carbon NMR spectra were recorded on
Bruker Advance DRX 2000 instrument. Electron impact (EI)
mass spectra were recorded on a Jeol JMS-D-300 spectrometer
with the ionization potential of 70 eV. Elemental analyses
were carried out on a CarloeErba EA 1108 instrument.
5.4. 1-Thiomethyl-1-N-( p-fluorophenyl amino)-5-
(20,60,60-trimethyl)-cyclohex-20-en-10-yl-pent-1,4-dien-3-
one (2d)
5.1. 1-Thiomethyl-1-N-phenyl amino-5-(20,60,60-trimethyl)-
cyclohex-20-en-10-yl-pent 1,4-dien-3-one (2a)
1
IR (neat, cmꢂ1) 3020, 2933, 1548, 1200, 750; H NMR
(CDCl3, 200 MHz) d 1.10 (s, 6H), 1.45 (m, 2H), 1.60 (m,
2H), 1.75 (s, 3H), 2.00 (m, 2H), 2.25 (s, 3H), 5.25 (s, 1H),
6.10 (d, J ¼ 16.00 Hz, 1H), 6.95 (d, J ¼ 16.00 Hz, 1H), 7.25
(m, 4H); 13C NMR (200 MHz) d 14.830 (q), 19.455 (t),
22.120 (q), 2 ꢁ 29.250 (q), 33.815 (t), 34.554 (s), 40.177 (t),
93.376 (d), 115.934 (d), 116.385 (d), 127.279 (d), 127.446
(d), 132.241 (d), 133.962 (s), 134.878 (s), 135.711 (s),
137.094 (s), 138.718 (s), 167.574 (s), 184.394 (s); MS: m/e
360 (mþ þ 1), 312 (mþ ꢂ SCH3). Anal. calcd. for
C21H26NSOF: C, 70.16; H, 7.28; N, 3.90. Found C, 70.25;
H, 7.30; N, 3.82.
To a solution of ketene dithioacetal 1 (0.296 g, 1 mmol) in
absolute ethanol (20 ml) was added aniline (0.932 g, 10 mmol)
and the resulting reaction mixture was heated in a steel bomb
at 100e105 ꢀC for 9 h. It was concentrated in vacuo and the
residue was column chromatographed (SiO2, 60e120 mesh).
Elution with 2% ethylacetate in hexane furnished 2a (0.20 g,
1
59%) as a pale brown oil. IR (neat, cmꢂ1) 2927, 1552; H
NMR (CDCl3, 200 MHz) d 1.10 (s, 6H), 1.50 (m, 2H), 1.60
(m, 2H), 1.80 (s, 3H), 2.00 (m, 2H), 2.40 (s, 3H), 5.10 (s,
1H), 6.10 (d, J ¼ 16.00 Hz, 1H), 7.30 (m, 6H), 13.60 (s,
1H); 13C NMR (CDCl3, 200 MHz) d 15.042 (q), 19.506 (t),
22.180 (q), 2 ꢁ 29.311 (q), 33.358 (t), 34.621 (s), 40.232 (t),
93.550 (d), 2 ꢁ 125.271 (d), 126.489 (d), 2 ꢁ 129.387 (d),
132.428 (d), 133.893 (s), 137.196 (s), 138.703 (s), 138.895
(d), 167.233 (s), 184.436 (s); MS: m/e 342 (mþ), 295
(mþ ꢂ SCH3). Anal. calcd. for C21H27NOS: C, 73.86; H,
7.97; N, 4.10. Found: C, 74.0; H, 7.88; N, 4.20.
5.5. 1-Thiomethyl-1-N-(3-fluorophenyl amino)-5-
(20,60,60-trimethyl)-cyclohex-20-en-10-yl-pent-1,4-dien-3-
one (2e)
1
IR (neat, cmꢂ1) 3400, 3020, 2931, 1550, 1215; H NMR
(CDCl3, 200 MHz) d 1.00 (s, 6H), 1.45 (m, 2H), 1.60 (m,
2H), 1.80 (s, 3H), 2.00 (m, 2H), 2.40 (s, 3H), 5.20 (s, 1H),
6.10 (d, J ¼ 16.00 Hz, 1H), 6.85 (d, J ¼ 16.00 Hz, 1H), 7.25
(m, 4H); 13C NMR (CDCl3, 200 MHz) d 15.08 (q), 19.458
(t), 22.167 (q), 2 ꢁ 29.282 (q), 33.879 (t), 34.598 (s), 40.212
(t), 94.310 (d), 120.357 (d), 120.418 (d), 130.449 (d),
130.634 (d), 2 ꢁ 132.081 (d,s), 134.328 (s), 137.107 (s),
2 ꢁ 139.163 (d,s), 167.477 (s), 184.570 (s); MS: m/e 360
(mþ þ 1), 344 (mþ ꢂ CH3), 312 (mþ ꢂ SCH3). Anal. calcd.
5.2. 1-Thiomethyl-1-N-( p-methoxyphenyl amino)-5-
(20,60,60-trimethyl)-cyclohex-20-en-10-yl-pent-1,4-dien-3-
one (2b)
IR (neat, cmꢂ1) 3433, 1639, 1217; 1H NMR (CDCl3,
200 MHz) d 1.10 (s, 6H), 1.50 (m, 2H), 1.65 (m, 2H), 1.80
(s, 3H), 2.10 (m, 2H), 2.35 (s, 3H), 2.50 (m, 2H), 3.80 (s,
3H), 5.25 (s, 1H), 6.00 (d, J ¼ 16.00 Hz, 1H), 6.80 (d,

S.N. Suryawanshi et al. / European Journal of Medicinal Chemistry 42 (2007) 511e516
515
for. C21H26NSOF: C, 70.16; H, 7.28; N, 3.90. Found C, 70.01;
H, 7.18; N, 3.82.
132.765 (s), 134.322 (d), 136.858 (d), 137.235 (s), 166.118 (s),
184.511 (s); MS: m/e 374 (mþ). Anal. calcd. for: C22H34N2O3:
C, 70.55; H, 9.15; N, 7.48. Found: C, 70.62; H, 9.57; N, 7.50.
5.6. 1-Thiomethyl-1-cyclohexyl amino-5-(20,60,60-
trimethyl)-cyclohex-20-en-10-yl-pent-1,4-dien-3-one (2f)
5.10. 1,1-Diaminoethyl-5-(20,60,60-trimethyl)-cyclohex-
20-en-10-yl-pent-1,4-dien-3-one (3c)
M.p. 75e76 ꢀC; IR (KBr, cmꢂ1) 3394, 2935, 1662, 1554,
1
1215; H NMR (CDCl3, 200 MHz) d 1.00 (m, 6H), 1.40 (m,
M.p. 195e196 ꢀC; IR (KBr, cmꢂ1) 3400, 3018, 2916, 1710,
1
1595; H NMR (CDCl3, 200 MHz) d 1.04 (s, 6H), 1.45 (m,
12H), 1.80 (s, 3H), 2.00 (m, 2H), 2.40 (s, 3H), 3.60 (m,
1H), 5.00 (s, 1H), 6.00 (d, J ¼ 16.00 Hz, 1H), 7.20 (d,
J ¼ 16.00 Hz, 1H); 13C NMR (CDCl3, 200 MHz) d 14.531
(q), 19.525 (t), 22.123 (q), 2 ꢁ 24.809 (t), 25.779 (t),
2 ꢁ 29.265 (q), 2 ꢁ 33.57 (t), 33.702 (t), 34.573 (s), 40.161
(t), 53.339 (d), 90.778 (d), 132.619 (s), 133.147 (d), 137.270
(d), 137.359 (s), 168.010 (s), 183.345 (s); MS: m/e 347
(mþ), 299 (mþ ꢂ SCH3). Anal. calcd. for C21H33ONS: C,
72.88; H, 9.91; N, 4.03. Found: C, 72.88; H, 10.15; N, 4.69.
2H), 1.55 (m, 2H), 1.75 (s, 3H), 2.00 (m, 2H), 3.65 (m, 2H),
4.80 (m, 2H), 5.95 (d, J ¼ 16.00 Hz, 1H), 7.06 (s, 1H), 7.10
(d, J ¼ 16.00 Hz, 1H); 13C NMR (200 MHz) d 19.568 (t),
22.034 (q), 2 ꢁ 29.246 (q), 33.622 (t), 34.561 (s), 40.164 (t),
2 ꢁ 43.565 (t), 78.888 (d), 131.838 (s), 133.583 (d), 135.506
(d), 137.390 (s), 165.895 (s), 184.005 (s); MS: m/e 262
(mþ þ 2). Anal. calcd. for: C16H24N2O: C, 72.52; H, 7.69;
N, 15.38. Found: C, 72.57; H, 8.01; N, 15.41.
5.7. 1-Thiomethyl-1-(N-ethyl-N-phenyl amino)-5-
(20,60,60-trimethyl)-cyclohex-20-en-10-yl-pent-1,4-dien-3-
one (2g)
Acknowledgements
Financial support from NOVA-NORDIX, DOD and ICMR
is gratefully acknowledged. Technical assistance by Mrs.
Manju and Shiv Ram is gratefully acknowledged.
1
IR (KBr, cmꢂ1) 3020, 1558, 1473, 1215, 760; H NMR
(CDCl3, 200 MHz) d 1.10 (s, 6H), 1.45 (m, 2H), 1.60 (m,
2H), 1.75 (s, 3H), 2.00 (m, 2H), 2.40 (s, 3H), 2.95 (m, 3H),
3.55 (m, 2H), 5.00 (s, 1H), 6.05 (d, J ¼ 16.00 Hz, 1H), 7.30
(m, 6H); 13C NMR (CDCl3, 200 MHz) d 14.578 (q), 19.544
(q), 22.167 (q), 2 ꢁ 29.310 (q), 33.782 (t), 34.605 (s),
36.702 (t), 40.218 (t), 46.135 (t), 91.218 (d), 127.033 (d),
4 ꢁ 129.115 (d), 132.928 (d), 133.063 (s), 137.272 (s),
137.584 (d), 138.737 (s); MS: m/e 370 (mþ þ 1). Anal. calcd.
for C23H31NOS: C, 74.75; H, 8.45; N, 3.79. Found: C, 74.51;
H, 8.37; N, 3.82.
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5.8. 1,1-Dipiperazino-5-(20,60,60-trimethyl)-cyclohex-20-
en-10-yl-pent-1,4-dien-3-one (3a)
IR (neat, cmꢂ1) 3419, 2927, 1500; 1H NMR (CDCl3,
200 MHz) d 1.00 (s, 6H), 1.45 (m, 2H), 1.45 (m, 1H), 1.55
(m, 2H), 1.75 (s, 3H), 2.00 (m, 2H), 2.80 (m, 8H), 3.20 (m,
8H), 4.45 (s, 1H), 6.00 (d, J ¼ 16.00 Hz, 1H), 7.08 (d,
J ¼ 16.00 Hz, 1H); 13C NMR (CDCl3, 200 MHz) d 19.507
(t), 22.141 (q), 2 ꢁ 29.299 (q), 33.704 (s), 34.537 (t), 40.212
(t), 4 ꢁ 46.45 (t), 4 ꢁ 50.055 (t), 88.585 (d), 132.501 (s),
134.464 (d), 136.259 (d), 137.264 (s), 167.087 (s), 184.026
(s); MS: m/e 372 (mþ).
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1440, 1363; H NMR (CDCl3, 200 MHz) d 1.00 (s, 6H), 1.40
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