A simple and efficient stereoselective synthesis of (-)-cleistenolide

Article abstract of DOI:10.1016/j.tetlet.2012.01.123

A simple and straightforward stereoselective synthesis of α,β-unsaturated δ-lactone, (-)-cleistenolide has been accomplished in 10 steps in an overall yield of 19%, starting from inexpensive and commercially available starting materials, respectively. This linear synthesis utilizes Sharpless asymmetric dihydroxylation, sulfur ylide mediated epoxide opening followed by ring-closing metathesis (RCM) for the formation of six-membered lactone ring as the key step sequence.

Full text of DOI:10.1016/j.tetlet.2012.01.123

Tetrahedron Letters 53 (2012) 1823–1825
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Tetrahedron Letters
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A simple and efficient stereoselective synthesis of (ꢀ)-cleistenolide
⇑
T. Vijaya Kumar, K. Suresh Babu, J. Madhusudana Rao
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and straightforward stereoselective synthesis of
a
,b-unsaturated d-lactone, (ꢀ)-cleistenolide
Received 1 November 2011
Revised 26 January 2012
Accepted 28 January 2012
Available online 3 February 2012
has been accomplished in 10 steps in an overall yield of 19%, starting from inexpensive and commercially
available starting materials, respectively. This linear synthesis utilizes Sharpless asymmetric dihydroxy-
lation, sulfur ylide mediated epoxide opening followed by ring-closing metathesis (RCM) for the forma-
tion of six-membered lactone ring as the key step sequence.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
(ꢀ)-Cleistenolide
Antibacterial
Appel reaction
Sharpless dihydroxylation
Ring-closing metathesis
Natural products possessing
has long been a privileged scaffold in drug discovery because of
a
,b-unsaturated d-lactone motif,
of many synthetic methods for this class of compounds, there still
exists a need to develop procedures more efficient than those cur-
rently in existence. In continuation of our ongoing studies on the
synthesis of bioactive natural products,6 we have focused on the
synthesis of (ꢀ)-cleistenolide because of its potential biological
activities. Herein, we report short and straightforward stereoselec-
their diverse array of biological activities including their antifungal
and antitumour properties.1
a,b-Unsaturated d-lactone unit is pre-
sumed to be an active pharmacophore responsible for biological
activities as a result of its ability to act as a Michael acceptor.2
Among these lactones, 5-hydroxy-a,b-unsaturated d-lactones have
tive synthesis of (ꢀ)-cleistenolide starting from
D-mannitol derived
attracted considerable attention due to their broad range of biolog-
ical activities. Representative examples of this class of molecules
are cleistenolide (1), pectinolide A (2), phomopsolide D (3), and
acetylphomolactone (4) (Fig. 1). Cleistenolide (1), perhaps is the
best example of these interesting compounds that have been iso-
lated from the medicinal plant Cleistochlamys kirkii oliver,3 that be-
longs to the family of annonaceae species with its origin from
Tanzania and Mozambique. Cleistenolide (1) exhibits in vitro anti-
bacterial activity against Staphylococcus aureus, Bacillus anthracis
and antifungal activity against Candida albicans. Moreover, the ex-
tracts of this plant have been utilized for the treatment of wound
infections, rheumatism, and tuberculosis.4
ester (S,E)-ethyl 3-(2,2-dimethyl-1,3-dioxolan-4-yl) with an over-
all yield of 19%. The synthesis involved the Sharpless asymmetric
dihydroxylation, sulfur ylide mediated epoxide ring opening and
Grubbs ring-closing metathesis as the key reaction sequence.
Our retrosynthetic analysis of the target compound (ꢀ)-clei-
stenolide is outlined in Scheme 1. As indicated, the cyclic frame
work of 1 could be constructed by ring-closing metathesis (RCM)
followed by PCC oxidation. The requisite diene 5, in turn, could
be accessed from the key intermediate 6 through allylation
O
O
3
4
O1
2
5
O
Owing to this combination of interesting structural features and
potential biological activities of cleistenolide (1), synthesis of this
compound has attracted much attention among organic chemists.
Consequently, several syntheses have appeared in the literature.
To date, only five total syntheses have been reported.5 The first
synthesis was reported by Schmidt et al.,5a using the mannitol de-
rived (R,R)-1,5-hexadiene-3,4-diol as a starting material and other
OAc
O
6
O
OAcOAc
OAc
(-)-Cleistenolide (1)
Pectinolide A (2)
O
O
O
O
OH
syntheses were achieved using D D
-arabinose,5b -mannitol,5c,d and
O
O
OAc
(ꢀ)-isoascorbic acid5e as starting materials. Despite the availability
OH
Phomopsolide D (3) (+)-Acetylphomolactone (4)
⇑
Figure 1. Reperesentative structures of some 5-substituted
lactones.
a,b-unsaturated d-
Corresponding author. Tel.: +91 40 27193166; fax: +91 40 27160512.
E-mail address: janaswamy@iict.res.in (J. Madhusudana Rao).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.01.123

1824
T. Vijaya Kumar et al. / Tetrahedron Letters 53 (2012) 1823–1825
further purification, was treated with powdered NaOH in dry THF
OAc OAc
OAcOAc
O
BzO
O
to give epoxide in a 79% yield as the key intermediate (over two
O
O
steps) with 95% ee.9
O
5
RCM
O
O
O
OH
The hydroxyl group in the key intermediate 6 was allylated
using NaH and allyl bromide in THF to afford 10 in a 95% yield.
With the allylated epoxide 10 in hand, we then shifted our focus
to the regioselective ring opening of epoxide with dimethylsulfo-
nium methylide (Me3SI, n-BuLi) to afford allylic alcohol 11 in a
94% yield,11 which was then acetylated with acetic anhydride in
the presence of triethylamine and a catalytic amount of DMAP
furnished the corresponding ester 12. Subsequent acetonide depro-
tection with 60% aq AcOH afforded diol 13 in a 75% yield. Benzoyl-
ation of primary alcohol in 13 was with benzoyl chloride in the
presence of pyridine in CH2Cl2 that gave the mono-benzoate which
was, without further purification, acetylated by the addition of ace-
tic anhydride to yield the triester 5 in an 80% yield. As mentioned
in our retrosynthetic analysis, next stage of our plan involved the
construction of six-membered d-lactone ring by ring-closing
metathesis. This may be considered as the most critical step in
our synthetic scheme because the preparation of medium-sized
rings by RCM may be difficult in some instances (especially from
acyclic precursors) owing to entropic factors and transannular
repulsions that develop as the ring is formed. Gratifyingly, and in
spite of these potential problems, in our case treatment of 5 with
Grubb’s second generation catalyst (5 mol %) in dry DCM under re-
flux conditions yielded 14 in a 90% yield. Finally, the allylic meth-
ylene group in 14 was oxidized with PCC and pyridine in dry DCM
that furnished the target compound, (ꢀ)-cleistenolide (1) in a 72%
yield (Scheme 2).12 The spectral data13 (1H NMR, 13C NMR, and
Mass data) derived from each of the intermediate compounds were
in full accordance with those of the assigned structures. Further-
more, chirooptical data, spectroscopic, and physical data of com-
pound 1 were identical in all respects to the data reported in the
literature.3,5a,b
6
1
O
O
O
O
Cl
OEt
D-Mannitol
O
7
8
Scheme 1. Retrosynthetic analysis of 1.
O
a
O
O
f
O
c
b
O
O
O
O
O
OEt
O
OH
Cl
O
OH
8
9
6
7
O
OH
O
OAc
O
g
O
e
O
O
d
O
O
O
10
OH OAc
11
12
OAcOAc
OAcOAc
O
HO
i
O
h
O
O
O
O
O
5
13
14
j
OAcOAc
O
O
O
O
1
Scheme 2. Reagents and conditions: (a) DIBAL-H, CH2Cl2, 0 °C, 3 h, 91%; (b) PPh3,
CCl4, NaHCO3, reflux, 6 h, 75%; (c) (i) AD-mix-b, CH3SO2NH2, NaHCO3, tBuOH/H2O,
0 °C, 24 h; (ii) NaOH, THF, 2 h, 0 °C–rt, 79% (over two steps); (d) allyl bromide, NaH,
THF, 0 °C–rt, 3 h, 95%; (e) (CH3)3S+Iꢀ, n-BuLi, ꢀ20 °C, 2 h, 94%; (f) Ac2O, Et3N, DMAP,
CH2Cl2, 0 °C–rt, 1 h, 95%; (g) 60% aq AcOH, 0 °C–rt, 12 h, 90%; (h) (i) Py, BzCl, CH2Cl2,
0 °C–rt, 4 h; (ii) Ac2O, 0 °C–rt, 4 h, 71% (over two steps); (i) Grubbs-II, CH2Cl2, reflux,
30 min, 90%; (j) PCC, Py, CH2Cl2, reflux, 8 h, 72%.
In conclusion, the stereoselective total synthesis of (ꢀ)-clei-
stenolide has been achieved by employing Sharpless asymmetric
dihydroxylation, sulfurylide mediated epoxide opening and ring
closing metathesis reactions as the key reaction sequence. On the
basis of the route described herein, further work toward prepara-
tion of the library of analogues for biological analysis is in progress
at our laboratory.
followed by sulfur ylide mediated epoxide ring opening. The key
intermediate 6 could be obtained from Sharpless dihydroxylation
of 7, which was derived from
egy, as a whole, relies on chiral starting material,
D
-mannitol in a few steps. This strat-
-mannitol and
D
its derivative 6 as the key reaction intermediate. The key step
was the highly stereospecific Sharpless dihydroxylation of manni-
tol derived ester 8 (Scheme 1). Although, our synthetic strategy
Acknowledgment
T.V.K. thanks the CSIR, New Delhi, India, for the financial sup-
port in the form of fellowship.
also utilized D-mannitol as a starting material, we have success-
fully implemented a strategy that minimizes protecting group
manipulation in a unique fashion, a common and unavoidable
practice in (ꢀ)-cleistenolide synthesis.
References and notes
1. Davies-Coleman, M. T.; Rivett, D. E. A. In Progress in the Chemistry of Organic
Natural Products; Herz, W., Grisebach, H., Kirby, G. W., Tamm, C., Eds.; Springer-
Verlag: Wien and New York, 1989; Vol. 55, pp 1–35.
2. (a) de Fatima, A.; Kohn, L. K.; de Carvalho, J. E.; Pilli, R. A. Bioorg. Med. Chem.
2006, 14, 622–631; (b) Buck, S. B.; Hardouin, C.; Ichikawa, S.; Soenen, D. R.;
Gauss, C. M.; Hwang, I.; Swingle, M. R.; Bonness, . M.; Honkanen, R. E.; Boger, D.
L. J. Am. Chem. Soc. 2003, 125, 15694–15695; (c) Kumar, P.; Naidu, S. V. J. Org.
Chem. 2006, 71, 3935–3941; (d) Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int.
Ed. Engl. 1985, 24, 94–110.
As shown in Scheme 2, the synthesis of cleistenolide was
started from enantiomerically pure (S,E)-ethyl 3-(2,2-dimethyl-
1,3-dioxolan-4-yl)acrylate 8, which was prepared from commer-
cially available D
-mannitol using the literature procedure.7 The es-
ter functionality in compound 8 was reduced to alcohol using
DIBAL-H to furnish the corresponding allylic alcohol 9 in an excel-
lent yield (91%). The stereochemistry of the double bond in 9 was
confirmed as E by the large coupling constant (J = 15 Hz) observed
from the 1H NMR spectrum. Next, we have investigated the Sharp-
less asymmetric dihydroxylation8 to install the two stereogenic
centers in 1. It is well known that allylic chlorides are excellent
substrates for Sharpless asymmetric dihydroxylation.9
With this view, hydroxyl functionality in 9 was subjected to the
Appel reaction conditions (triphenyl phosphine, CCl4, reflux)10 to
afford its corresponding allylic chloride 7. Subsequently, this allyl
chloride 7 was subjected to Sharpless asymmetric dihydroxylation
using AD-mix-b to give intermediate chloro-diol, which, without
3. Samwel, S.; Mdachi, S. J. M.; Nkunya, M. H. H.; Irungu, B. N.; Moshi, M. J.;
Moulton, B.; Luisi, B. S. Nat. Prod. Commun. 2007, 2, 737–741.
4. Nkunya, M. H. H. Pure Appl. Chem. 2005, 77, 1943–1955.
5. (a) Schmidt, B.; Kunz, O.; Biernat, A. J. Org. Chem. 2010, 75, 2389–2394; (b)
Chao, C.; Jun, L.; Yuguo, D.; Robert, J. L. J. Org. Chem. 2010, 75, 5754–5756; (c)
Ramesh, P.; Meshram, H. M. Tetrahedron Lett. 2011, 52, 2443–2445; (d) Subba
Reddy, B. V.; Reddy, B. P.; Pandurangam, T.; Yadav, J. S. Tetrahedron Lett. 2011,
52, 2306–2308; (e) Chanti babu, D.; Jhon paul selvam, J.; Kumar reddy, D.;
Shekar, Y.; Venkateshwarlu, V. Tetrahedron 2011, 67, 3815–3819.
6. (a) Shankaraiah, G.; Kumar, R. S. C.; Poornima, B.; Babu, K. S. Tetrahedron Lett.
2011, 52, 4885–4887; (b) Kumar, R. S. C.; Reddy, G. V.; Babu, K. S.; Rao, J. M.
Tetrahedron Lett. 2011, 52, 4382–4384; (c) Sreedhar, E.; Venkanna, A.;
Chandramouli, N.; Babu, K. S.; Rao, J. M. Eur. J. Org. Chem. 2011, 1078–1083;

T. Vijaya Kumar et al. / Tetrahedron Letters 53 (2012) 1823–1825
1825
(d) Kumar, R. S. C.; Reddy, G. V.; Shankaraiah, G.; Babu, K. S.; Rao, J. M.
Tetrahedron Lett. 2010, 51, 1114–1116; (e) Reddy, G. V.; Kumar, R. S. C.;
Sreedhar, E.; Babu, K. S.; Rao, J. M. Tetrahedron Lett. 2010, 51, 1723–1726; (f)
Reddy, G. V.; Kumar, R. S. C.; Babu, K. S.; Rao, J. M. Tetrahedron Lett. 2009, 50,
4117–4120; (g) Kumar, R. S. C.; Sreedhar, E.; Reddy, G. V.; Babu, K. S.; Rao, J. M.
Tetrahedron: Asymmetry 2009, 20, 1160–1163; (h) Sreedhar, E.; Kumar, R. S. C.;
Reddy, G. V.; Robinson, A.; Babu, K. S.; Rao, J. M. Tetrahedron: Asymmetry 2009,
20, 440–448.
924 cmꢀ1 1H NMR (CDCl3, 300 MHz): 1.32 (s, 3H), 1.40 (s, 3H), 3.42–3.45 (m,
;
1H), 3.84–3.91 (m, 1H), 3.98–4.05 (m, 1H), 4.09–4.20 (m, 4H), 5.15–5.38 (m,
3H), 5.81–5.89 (m, 1H), 5.90–5.97 (m, 1H); 13C NMR (CDCl3, 75 MHz): d 25.3,
26.5, 66.3, 72.1, 73.3, 75.8, 80.8, 109.1, 116.1, 117.5, 134.3, 137.5; ESIMS m/z
251 (M+Na)+; ESI-HRMS: m/z calcd for C12H20O4Na: 251.12538, found:
251.12505.
(1S,2R)-1-(Allyloxy)-1-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)but-3-en-2-yl acetate
(13): ½a 2D5
ꢁ
+20.4 (c 0.5, CHCl3); IR (KBr) mmax 3077, 2937, 1740, 1451, 1372,
7. Takano, S.; Kurotaki, A.; Takahashi, M.; Ogasawara, K. Synthesis 1986, 403–406.
8. Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483.
9. VanHessche, K. P. M.; Wang, Z.-M.; Sharpless, K. B. Tetrahedron Lett. 1994, 35,
3469.
10. Gowrisankar, P.; Pujari, S. A.; Kaliappan, K. P. Chem. Eur. J. 2010, 16, 5858–5862.
11. Alcarez, L.; Hamett, J. J.; Mioskowski, C.; Martel, J. P.; Le Gall, T.; Shin, D.-S.;
Falck, J. R. Tetrahedron Lett. 1994, 35, 5449.
1277, 1236, 714 cmꢀ1 1H NMR (CDCl3, 300 MHz): 1.31 (s, 3H), 1.38 (s, 3H),
;
2.09 (s, 3H), 3.61 (t, 1H), 3.86–3.95 (m, 2H), 4.03–4.1 (m, 1H), 4.15–4.19 (m,
2H), 5.13–5.18 (m, 1H), 5.22–5.34 (m, 4H), 5.78–5.93 (m, 2H); 13C NMR (CDCl3,
75 MHz): d 21.1, 25.4, 26.3, 65.3, 73.8, 74.1, 75.7, 76.7, 108.6, 117.3, 118.1,
133.2, 134.4, 169.8; ESIMS m/z 293 (M+Na)+; ESI-HRMS: m/z calcd for
C
14H22O5Na: 293.13594, found: 293.13585.
(3R,4R,5S)-4-(Allyloxy)-5,6-dihydroxyhex-1-en-3-yl acetate (14): ½a D25
ꢁ
+35 (c 0.5,
12. Srikanth, G. S. C.; Murali Krishna, U.; Trivedia, G. K.; Cannon, J. F. Tetrahedron
2006, 62, 11165–11171.
CHCl3); IR (KBr) mmax 3435, 2932, 1733, 1374, 1247, 1087, 1024, 928 cmꢀ1 1H
;
NMR (CDCl3, 300 MHz): 2.15 (s, 3H), 3.45–3.54 (m, 2H), 3.62–3.68 (m, 1H),
3.72–3.78 (m, 1H), 4.06–4.17 (m, 2H), 5.13–5.40 (m, 4H), 5.48–5.52 (m, 1H),
5.80–6.0 (m, 2H); 13C NMR (CDCl3, 75 MHz): d 21.09, 63.06, 70.4, 74, 74.2, 80.8,
117.6, 118, 133.4, 134.1, 171.1; ESIMS m/z 253 (M+Na)+; ESI-HRMS: m/z calcd
for C11H18O5Na: 253.10464, found: 253.10449.
13. Spectral data:
(2E,4S)-4,5-(O-Isopropylidene)-4,5-dihydroxyprop-2-en-1-ol (10): ½a D25
ꢁ
+30.5 (c
1, CHCl3); IR (KBr) mmax 3414, 2988, 1721, 1689, 1377, 1216, 1157, 1061,
976 cmꢀ1 1H NMR (CDCl3, 300 MHz): 1.35 (s, 3H), 1.39 (s, 3H), 3.54 (t, J = 7.9,
;
15.8 Hz, 1H), 4.04 (br t, J = 7.9, 13.8 Hz, 1H), 4.13 (d, J = 4 Hz, 2H), 4.48 (dd,
J = 6.9, 13.8 Hz, 1H), 5.67 (dd, J = 6.9, 14.8 Hz, 1H) 5.91 (dt, J = 4.94, 14.8 Hz,
1H); 13C NMR (CDCl3, 75 MHz): d 25.7, 26.5, 62.3, 69.2, 76.4, 109.2, 128.1;
ESIMS m/z 181 (M+Na)+; ESI-HRMS: m/z calcd for C8H14O3Na: 181.14352,
found: 181.14375.
(2S,3S,4R)-3-(Allyloxy)-1-(benzoyloxy)hex-5-ene-2,4-diyldiacetate (15): ½a D25
ꢁ
+42
(c 0.1, CHCl3); IR (KBr) mmax 3085, 2988, 2937, 1745, 1646, 1427, 1373, 1233,
1024 cmꢀ1 1H NMR (CDCl3, 300 MHz): 2.03 (s, 3H), 2.09 (s, 3H), 3.74 (dd,
;
J = 3.7, 7.3, 1H), 4.08–4.2 (m, 2H), 4.41 (dd, J = 5.6, 12.2, 1H), 4.65 (dd, J = 2.2,
12.2, 1H), 5.14–5.48 (m, 6H), 5.8–5.98 (m, 2H), 7.43 (t, J = 7.7, 2H), 7.55 (t,
J = 7.5, 1H), 8.0 (d, J = 7.3, 1H); 13C NMR (CDCl3, 75 MHz): d 20.9, 20.1, 70.0,
73.1, 73.9, 78.4, 118, 118.7, 128.4, 129.5, 132.7, 133.1, 133.8, 166.1, 169.8,
170.05; ESIMS m/z 399 (M+Na)+; ESI-HRMS: m/z calcd for C20H24O7Na:
399.14142, found: 399.14143.
(S,E)-4-(3-Chloroprop-1-enyl)-2,2-dimethyl-1,3-dioxolane (7): ½a D25
ꢁ
+20 (c 0.5,
CHCl3); IR (KBr) m ;
max 2924, 2857, 1725, 1448, 1101, 972 cmꢀ1 1H NMR (CDCl3,
300 MHz): 1.36 (3H, s), 1.40 (3H, s), 3.57 (t, J = 7.9, 15.8 Hz, 1H), 4.02–4.05 (m,
2H), 4.08 (br t, J = 7.9, 14.8, 1H), 4.49 (dd, J = 6.9, 13.8 Hz, 1H), 5.76 (dd, J = 6.9,
14.8 Hz, 1H) 5.91 (dt, J = 4.94, 14.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d 25.7,
26.6, 43.8, 69.1, 75.8, 109.5, 129.3, 132; ESIMS m/z 177 (M+H)+: ESI-HRMS: m/z
calcd for C8H13ClO2: 177.85246, found: 177.92344.
(S)-2-Acetoxy-2-((2S,3R)-3-acetoxy-3,6-dihydro-2H-pyran-2-yl)ethyl
benzoate
ꢀ163.5 (c 1, CHCl3); IR (KBr) mmax 2972,
1H NMR (CDCl3,
(5): white solid, mp 62–64 °C; ½a D25
ꢁ
1744, 1601, 1450, 1374, 1279, 1232, 1099, 714 cmꢀ1
;
(S)-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)((R)-oxiran-2-yl)methanol (6): ½a D25
ꢁ
ꢀ20
300 MHz): 2.01 (s, 3H), 2.06 (s, 3H), 3.82–3.87 (m, 1H), 4.12–4.21 (m, 1H),
4.29–4.38 (m, 1H), 4.45 (dd, J = 5.09, 12.08, 1H), 4.7 (dd, J = 2.26, 12.08, 1H),
5.15–5.22 (m, 1H), 5.34 (ddd, J = 9.4, 5.0, 2.2, 1H), 5.91–6.0 (m, 1H), 6.03–6.12
(m, 1H), 7.43 (t, J = 7.5, 2H), 7.54 (t, J = 7.3, 1H), 8.0 (d, J = 7.17, 2H); 13C NMR
(CDCl3, 75 MHz): d 20.7, 20.8, 62.2, 63.3, 65.9, 60.7, 73.8, 96.2, 122.5, 128.3,
129.7, 130.1, 131.9, 132.8, 165.6, 169.1, 169.9; ESIMS m/z 371 (M+Na)+; ESI-
HRMS: m/z calcd for C18H20O7Na: 371.11012, found: 371.11058.
(c 0.75, CHCl3); IR (KBr) mmax 3440, 2990, 1640, 1377, 1256, 1216, 1155, 1066,
849 cmꢀ1 1H NMR (CDCl3, 300 MHz): 1.34 (s, 3H), 1.40 (s, 3H), 2.75–2.77 (m,
;
1H), 2.80–2.82 (m, 1H), 3.17–3.19 (m, 1H), 3.44–3.49 (m, 1H), 3.96 (dd, J = 4.9,
7.9, 1H), 4.02 (dd, J = 5.9, 12.8, 1H), 4.08 (dd, J = 5.9, 7.9, 1H); 13C NMR (CDCl3,
75 MHz): d 25.02, 26.5, 44.5, 52.4, 66.5, 71.2, 76.4, 109.5; ESIMS m/z 197
(M+Na)+; ESI-HRMS: m/z calcd for C8H14O4Na: 197.11025, found: 197.11062.
(S)-4-((S)-Allyloxy((R)-oxiran-2-yl)methyl)-2,2-dimethyl-1,3-dioxolane (11): ½a D25
ꢁ
(S)-2-Acetoxy-2-((2S,3R)-3-acetoxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)ethyl
ꢀ4.5 (c 0.5, CHCl3); IR (KBr) mmax 2926, 2856, 1459, 1375, 1257, 1075, 920,
benzoate (1); white solid, mp 130–134 °C; ½a D25
ꢁ
ꢀ160.6 (c 1, CHCl3); IR (KBr)
848 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): 1.32 (s, 3H), 1.36 (s, 3H), 2.54–2.58 (m,
mmax 2929, 1743, 1602, 1450, 1373, 1278, 1229, 1102, 714 cmꢀ1 1H NMR
;
1H), 2.76–2.80 (m, 1H), 2.87–2.96 (m, 2H), 2.54–2.58 (m, 1H), 4.01–4.09 (m,
3H), 4.29 (dd, J = 5.09, 12.8, 1H), 5.16 (d, J = 10.2, 1H), 5.26 (d, J = 18.1, 1H),
5.79–5.92 (m, 1H); 13C NMR (CDCl3, 75 MHz): d 25.02, 26.5, 43.7, 52.9, 67.02,
71.4, 75.4, 81.1, 109.4, 117.1, 134.3; ESIMS m/z 237 (M+Na)+; ESI-HRMS: m/z
calcd for C11H18O4Na: 237.09735, found:237.09532.
(CDCl3, 300 MHz): 2.02 (s, 3H), 2.09 (s, 3H), 4.5 (dd, J = 4.3, 12.4, 1H), 4.75 (dd,
J = 9.8, 2.6, 1H), 4.93 (dd, J = 12.2, 2.2, 1H), 5.39 (dd, J = 6.0, 2.6, 1H), 5.48 (ddd,
J = 9.6, 4.5, 2.4, 1H), 6.2 (d, J = 9.6, 1H), 6.9 (dd, J = 9.6, 6.0, 1H), 7.43 (t, J = 7.7,
2H), 7.55 (t, J = 7.5, 1H), 8.0 (d, J = 7.17, 2H); 13C NMR (CDCl3, 75 MHz): d 20.4,
20.6, 59.7, 61.9, 67.6, 75.4, 125.3, 128.4, 129.6, 133.2, 139.7, 161.05, 165.9,
169.4, 169.8; ESIMS m/z 385 (M+Na)+; ESI-HRMS: m/z calcd for C18H18O8Na:
385.08939, found: 385.08980.
(1S,2R)-1-(Allyloxy)-1-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)but-3-en-2-ol
(12):
½ ꢁ
a 2D5
+5 (c 0.5, CHCl3); IR (KBr) mmax 2925, 2856, 1458, 1375, 1218, 1070,