Stereoselective synthesis of tetrahydropyran-tetrahydrofuran (THP-THF) core of (+)-muconin via Prins cyclization

Article abstract of DOI:10.1016/j.tetlet.2014.02.096

A stereoselective synthesis of tetrahydropyran-tetrahydrofuran (THP-THF) core 2 of (+)-muconin (1) has been achieved using Prins cyclization as a key step to construct tetrahydropyran moiety. Other important transformations such as Wittig olefination, Sharpless epoxidation, regio-, and stereoselective exo-cyclization of the epoxy alcohol, titanocene induced regioselective deoxygenation of 2,3-epoxy alcohol, Grignard reaction, and Barton-McCombie reaction are successfully employed to accomplish the synthesis of THP-THF core 2.

Full text of DOI:10.1016/j.tetlet.2014.02.096

Accepted Manuscript
Stereoselective synthesis of tetrahydropyran-tetrahydrofuran (THP-THF) core
of (+)-muconin via Prins cyclization
J.S. Yadav, U.V. Subba Reddy, B.V. Subba Reddy
PII:
S0040-4039(14)00348-7
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.02.096
TETL 44283
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
18 January 2014
21 February 2014
24 February 2014
Please cite this article as: Yadav, J.S., Subba Reddy, U.V., Subba Reddy, B.V., Stereoselective synthesis of
tetrahydropyran-tetrahydrofuran (THP-THF) core of (+)-muconin via Prins cyclization, Tetrahedron Letters (2014),
doi: http://dx.doi.org/10.1016/j.tetlet.2014.02.096
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Graphical Abstract
Stereoselective synthesis of
Leave this area blank for abstract info.
tetrahydropyran-tetrahydrofuran (THP-THF)
core of (+)-muconin via Prins cyclization
J. S. Yadav,* U. V. Subba Reddy, B. V. Subba Reddy
O
O
O
OH
OH
O
OH
(+)-muconin

1
Tetrahedron Letters
j o u r n a l h o m e p a g e : w w w . e ls e v i e r . c o m
Stereoselective synthesis of tetrahydropyran-tetrahydrofuran (THP-THF) core
of (+)-muconin via Prins cyclization
J. S. Yadav,* U. V. Subba Reddy, B. V. Subba Reddy
Natural Product Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax: 91-40-27160512; E-mail:yadavpub@iict.res.in
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A stereoselective synthesis of tetrahydropyran-tetrahydrofuran (THP-THF) core 2
of (+)-muconin (1) has been achieved using Prins cyclization as a key step to
construct tetrahydropyran moiety. Other important transformations such as Wittig
olefination, Sharpless epoxidation, regio- and stereoselective exo-cyclization of
the epoxy alcohol, titanocene induced regioselective deoxygenation of 2,3-epoxy
alcohol, Grignard reaction, and Barton-McCombie reaction are successfully
employed to accomplish the synthesis of THP-THF core 2.
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved.
Muconin, Annonaceous acetogenins,
cytotoxicity, Sharpless epoxidation,
Grignard reaction, Prins cyclization
Annonaceous acetogenins are the important naturally
occurring polyketides isolated from the plants of
Annonaceae family. These are a novel class of rapidly
emerging natural products with promising biological
activities such as antitumor, antimalarial, antimicrobial,
antiprotozoal and pesticidal behaviour.1 They also act as
strong insecticides, acaricides, fungicides, antiparasitics
and herbicides. They are important inhibitors of complex
I (NADH: ubiquinone oxidoreductase) in mammalian
and insect mitochondrial electron transport systems2 and
are powerful inhibitors of NADH oxidase of the plasma
membranes of cancer cells.3 (+)-Muconin (1) is a rare
type of non-classical acetogenin bearing THP ring along
with adjacent THF ring and α,β-unsaturated γ-lactone
moiety. It was isolated by McLaughlin's group in 1996
from the leaves of Rollinia mucosa.4 It shows potent and
selective in vitro cytotoxicity against PACA-2
(pancreatic cancer) and MCF-7 (breast cancer) in a panel
of six human solid tumor cell lines.4 In contrast, THP-
THF core of the (+)-muconin (1) displays the modest
cytotoxicity GI50 values of 90 and 85 µM against the
human solid tumor cell lines A2780 and SW1573 cells
respectively.5 This clearly indicates that muconin (1) has
tremendous biological activity. Therefore, it has become
a challenge for synthetic chemists not only as a complex
key reaction. Retrosynthetic strategy of muconin (1) is
shown in Scheme 1.
O
O
O
OH
OH
O
OH
(+)-Muconin (1)
O
O
O
OBn
OTBS
O
+
2
OBn
SPh
3
+
OHC
O
C11H23
OH
OBn
OBn
4
5
OH
OH
CO2iPr
iPrO2C
OH
7
target but also as
a
promising lead molecule.
6
Consequently, several efforts have been made on its total
synthesis which resulted in six total syntheses6 and one
formal synthesis5 of the molecule.
Scheme 1. Retrosynthetic analysis of (+)-muconin (1)
As per our strategy, muconin (1) could be obtained by
the coupling of butenolide fragment 3 with THP-THF
core 2 through the cross-metathesis.8 THP-THF core 2
could be prepared by the coupling of fragments 4 and 5
Following our interest on the total synthesis of natural
products involving Prins cyclization,7 we herein report a
highly flexible and stereo-controlled synthesis of THP-
THF core 2 of (+)-muconin (1) via Prins cyclization as a

2
Tetrahedron
by Prins cyclization followed by deoxygenation through
under Swern conditions14 (using oxalyl chloride, DMSO
and triethylamine) followed by two-carbon homologation
with [(ethoxycarbonyl)methylene]triphenylphosphorane
in benzene gave the (E)-α,β-unsaturated ester 16 in 90%
overall yield for two steps. Reduction of the double bond
of 16 with NiCl2.6H2O and NaBH415 followed by
reduction of the ester with LAH gave the primary alcohol
18 in 85% yield. Conversion of the alcohol 18 into 19
was achieved in two steps i.e. oxidation of the primary
alcohol under Swern conditions followed by C2-Wittig
olefination. Reduction of the ester 19 with DIBAL-H
gave the allylic alcohol 20 in 80% isolated yield. The
compound 20 was further converted into chiral epoxy
alcohol 21 in 85% yield under Sharpless asymmetric
epoxidation conditions11 using (+)-DET, t-BuOOH and
Ti(OiPr)4 (Scheme 3).
Barton-McCombie reaction. The homoallylic alcohol 5
could be synthesized from hepta-6-ene-1-ol 7 and
aldehyde 4, which would be derived from (-)-DIPT (6)
using sequence of reactions such as Sharpless
epoxidation, Wittig olefination and Grignard reaction.
Synthesis of homoallyl alcohol (5)
Accordingly, the hepta-6-ene-1-ol 7 was converted
into aldehyde using IBX (2-Iodoxybenzoic acid)9 in
THF/DMSO. Wittig olefination10 of the aldehyde with
Ph3P=CHCO2Et gave the α,β-unsaturated ester 8 in 80%
yield. Reduction of the unsaturated ester 8 with DIBAL-
H furnished the allylic alcohol 9 in 82% yield, which was
then subjected to Sharpless asymmetric epoxidation
using (+)-DET to give the chiral epoxy alcohol 10 with
96% ee in 86% yield.11 Reductive regioselective ring
opening of the epoxide 10 using our own protocol
(titanium(III) in THF) furnished the allylic alcohol 11 in
88% yield.12 Asymmetric epoxidation of the allylic
alcohol 11 using (-)-DET, titanium(IV) isopropoxide and
tert-butylhydroperoxide in anhydrous dichloromethane
afforded the epoxy alcohol 12 with 92% de in 85% yield.
Protection of the secondary hydroxyl group 12 with
benzyl bromide in the presence of NaH gave the benzyl
ether 13. Regioselective ring opening of the terminal
epoxide 13 with vinyl magnesium bromide gave the
homoallylic alcohol 5 in excellent yield (Scheme 2).
OH
b
a
i
CO2 Pr
HO
OH
iPrO2C
O
O
OH
6
14
c
CO2Et
d
BnO
OH
BnO
O
O
O
O
O
O
15
16
CO2Et
f
e
OH
BnO
BnO
BnO
O
O
b
a
CO2Et
OH
18
17
7
8
CO2Et
g
OH
BnO
c
d
O
O
O
O
OH
OH
O
10
f
9
20
19
e
h
O
O
BnO
OH
O
O
O
OBn
OH
OH
13
11
12
21
Scheme 3. Reagents and conditions: a) i) 2,2-DMP, p-
TSA (cat), benzene, 0 °C - reflux, 78%; ii) LAH, THF, 0
°C – r.t, 90%; b) NaH, BnBr, THF, 0 °C – r.t, 80%; c) i)
(COCl)2, DMSO, Et3N, DCM, -78 °C; ii)
Ph3P=CHCO2Et, benzene, r.t, 6h, 90% (for 2 steps); d)
NiCl2.6H2O, NaBH4, MeOH, 0 °C – r.t, 82%; e) LAH,
THF, 0 °C - rt, 85%; f) i) (COCl)2, DMSO, Et3N, DCM, -
78 °C; ii) Ph3P=CHCO2Et, benzene, r.t, 6h, 90% (two
steps); g) DIBAL-H, CH2Cl2, -20 °C – r.t, 2h, 80%; h)
(+)-DET, Ti(OiPr)4, t-BuOOH, CH2Cl2, 4Å MS, -25 °C,
12h, 85%.
g
HO
OBn
5
Scheme 2. Reagents and conditions: a) i) IBX,
THF/DMSO, 0 °C–r.t, 4h; ii) Ph3P=CHCO2Et, benzene
r.t, 5h, 80%; b) DIBAL-H, CH2Cl2, -15 °C–r.t, 1h, 82%;
c) (+)-DET, Ti(OiPr)4, tBuOOH, CH2Cl2, 4Å MS, -25 °C,
6h, 86%; d) (C5H5)2TiCl, THF, r.t, 88%; e) (-)-DET,
Ti(OiPr)4, BuOOH, CH2Cl2, 4Å MS, -25 °C, 6h, 85%; f)
t
Further treatment of the epoxy alcohol 21 with 2,2-
dimethoxypropane in the presence of CSA
(camphorsulfonic acid) in dichloromethane gave the anti-
tetrahydrofuran (THF) 22 as a sole product in one step in
86% yield through a regio- and stereoselective exo-
cyclization.16 Reductive removal of the benzyl ether
using Pd-C/H2 followed by mono tosylation17 afforded
the tosyl derivative 24. Compound 24 was then exposed
to NaH to give the terminal epoxide 25 in 75% yield with
a retention of the chiral center. Regioselective opening of
the epoxide 25 with Grignard reagent prepared freshly
from 1-undecane bromide and magnesium gave the
NaH, BnBr, THF, 0 °C–r.t, 10h, 95%; g) vinyl bromide,
Mg, THF, -40 °C, 1h, 80%.
Synthesis of the aldehyde fragment (4)
Our synthetic approach for the preparation of aldehyde 4
began with (-)-diisopropyl tartrate (DIPT) 6. Protection
of 6 with 2,2-dimethoxypropane using p-TSA followed
by reduction with LAH in THF gave the diol 14 in 90%
yield. Selective mono protection of the diol 14 with
benzyl bromide and NaH furnished the monobenzyl ether
15 in 80% yield.13 Oxidation of the primary alcohol 15

3
hydroxy derivative 26 in 86% yield. The secondary
hydroxyl group of 26 was protected with benzyl bromide
in presence of NaH in THF to yield the benzyl ether 27.
Removal of the isopropylidene group followed by
oxidation of the diol using NaIO4 furnished the aldehyde
4 in 75% overall yield (Scheme 4).
C11H23
OHC
+
O
OH
OBn
OBn
4
5
a
a
b
HO
21
O
BnO
O
O
O
OH
O
HO
OH
O
O
C11H23
23
22
O
BnO
OBn
c
d
b
28
O
TsO
O
O
O
O
O
OH
O
24
25
O
O
OBn
e
f
O
O
C11H23
OBn
2
O
OH
26
Scheme 5. Reagents and conditions: a) i) TFA, CH2Cl2, 0
°C–r.t, 3h; ii) K2CO3, MeOH, 0 °C–r.t, 30 min, 55% (two
steps); b) i) CS2, MeI, NaH, THF, reflux, 6h, 85%; ii) n-
Bu3SnH, AIBN, toluene, reflux, 1h, 80%.
g
H
C11H23
C11H23
O
O
O
OBn
O
OBn
O
4
27
In conclusion, we have demonstrated a highly flexible
and stereo-controlled synthetic route for the synthesis of
tetrahydropyran-tetrahydrofuran (THP-THF) core 2 of
(+)-muconin (1) employing Wittig olefination, Sharpless
epoxidation, titanium(III) mediated reductive opening of
2,3-epoxy alcohol, regio- and stereoselective exo-
cyclization of the epoxy alcohol, regio-controlled
Scheme 4. Reagents and conditions: a) CSA, CH2Cl2, 0
°C, 5 min, 2,2-DMP, r.t, 2h, 86%; b) Pd/C(10%), H2,
EtOAc, r.t, 6h; c) Tosyl chloride, Et3N, CH2Cl2,
dibutyltinoxide, 2h, 75%; d) NaH, THF, 0 °C–r.t, 1h,
75%; e) n-C11H23Br, Mg, THF, -78 to 25 °C, 2h, 86%; f)
NaH, BnBr, THF, 0 °C–r.t, 6h, 85%; g) i) p-TSA,
MeOH, r.t, 2h; ii) NaIO4, THF/H2O (3:1), 75%.
Grignard reaction, Prins-cyclization and
Barton-
Coupling of 4 and 5
McCombie reaction. Studies towards the total synthesis
of (+)-muconin (1) through the coupling of fragments 2
and 3 is under progress.
The Prins cyclization has emerged as a powerful
synthetic tool for the construction of tetrahydropyran
scaffolds.18 Inspired by the versatility of Prins
cyclization, we attempted the coupling of homoallylic
alcohol 5 with aldehyde 4 using trifluoroacetic acid in
dichloromethane to produce the tetrahydropyranyl
trifluoroacetate. No side reactions or byproducts were
observed in Prins cyclization. But 15% unreacted
aldehyde was recovered. Upon hydrolysis of the
trifluoroacetate with K2CO3 in methanol furnished the
desired tetrahydropyran-tetrahydrofuran (THP-THF)
derivative 28 in 55% overall yield after two steps. The
reaction is a highly diastereoselective and the required
product 28 was obtained as a single diastereomer, which
was confirmed by NMR spectrum of the crude product.
The secondary hydroxyl group of 28 was converted into
its xanthate ester19 using NaH, CS2 and MeI in dry THF,
Acknowledgements
U.V.S.R thanks UGC, New Delhi for the award of
Fellowship. JSY thanks CSIR and DST, New Delhi for
Bhatnagar and J C Bose Fellowships respectively.
References and Notes
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Biochem. Physiol. 1993, 45, 15; c) Ahammadsahib,
K. I.; Hollingworth, R. M.; McGovern, J. P.; Hui,
Y.H.; McLaughlin, J. L. Life Sci. 1993, 53, 1113; d)
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Gadelhak, G.; McLaughlin, J. L. Biochem. Soc.
Trans. 1994, 22, 230.
followed
by
deoxygenation
(Barton-McCombie
reaction)20 using n-Bu3SnH and a cat. amount of AIBN in
toluene gave the target THP-THF core 2 in 80% yield
(Scheme 5).21

4
Tetrahedron
3. Morre, D. J.; de Cabo, R.; Farley, C.; Oberlies, N.
Kwon, M. S.; Woo, S. K.; Na, S. W.; Lee, E.
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Perkin Trans. 1, 1975, 1574.
21 Spectral data for selected compounds. ((2S,3S)-3-
20
(Hex-5-enyl)oxiran-2-yl)methanol (10): [α]D
+
6.24 (c = 0.83, CHCl3); IR (neat): υmax 3450, 2848,
1623, 770 cm-1; 1H NMR (CDCl3, 300 MHz): δ
5.83 - 5.69 (m, 1H), 5.02-4.89 (m, 2H), 3.90 - 3.81
(m, 1H), 3.64 - 3.53 (m, 1H), 2.94 - 2.83 (m, 2H),
2.30 (brs, 1H), 2.11 - 2.00 (m, 2H), 1.60 - 1.34 (m,
6H); 13C NMR (CDCl3, 75 MHz): δ 138.5, 114.5,
63.2, 61.6, 58.5, 31.2, 28.4, 26.2, 25.2; ESI-MS:
m/z: 179 (M+Na).
8. a) Zhu, L.; Mootoo, D. R. Org. Lett. 2003, 5, 3475;
b) James, A. M.; Jesse, J. S. Org. Lett. 2006, 8,
3557; c) Takahashi, S.; Hongo, Y.; Ogawa, N.;
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6305.
(S)-Nona-1,8-dien-3-ol (11): [α]D20 _15.23 (c = 0.8,
CHCl3); IR (neat): υmax 3420, 2915, 1640, 752 cm-1;
1H NMR (CDCl3, 300 MHz): δ 5.88 - 5.69 (m, 2H),
5.22 - 4.88 (m, 4H), 4.08 - 4.00 (m, 1H), 2.09 - 2.00
(m, 2H), 1.67 (bs, 1H), 1.55 - 1.25 (m, 6H); 13C
NMR (CDCl3, 75 MHz): δ 138.9, 137.8, 117.4,
114.1, 72.3, 37.0, 33.7, 29.1, 24.9; ESI-MS: m/z:
163 (M+Na).
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1994, 35, 8019.
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5765.
(S)-2-((S)-1-(Benzyloxy)hept-6-enyl)oxirane (13):
[α]D + 6.56 (c = 1.26, CHCl3); IR (neat): υmax
20
3016, 2963, 1631, 1482, 724 cm-1; 1H NMR
(CDCl3, 300 MHz): δ 7.34 - 7.25 (m, 5H), 5.82 -
5.68 (m, 1H), 5.01 - 4.89 (m, 2H), 4.53 (s, 2H), 3.23
- 3.16 (m, 1H), 2.86 - 2.82 (m, 1H), 2.74 - 2.69 (m,
1H), 2.67 - 2.63 (m, 1H), 2.09 - 1.99 (m, 2H), 1.64 -
1.36 (m, 6H); 13C NMR (CDCl3, 75 MHz): δ 138.8,
138.6, 128.38, 128.3, 127.7, 114.4, 78.0, 72.2, 53.5,
43.1, 33.6, 32.7, 28.9, 24.6; ESI-MS: m/z: 247
(M+H), 269 (M+Na).
12. Yadav, J. S.; Shekharam, T.; Gadgil, V. R. J. Chem.
Soc., Chem. Commun. 1990, 843.
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2396.
18. a) Barry, C. St.; Crosby, S. R.; Harding, J. R.;
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C. L. Org. Lett. 2003, 5, 2429; b) Yang, X. F.;
Mague, J. T.; Li, C. J. Org. Chem. 2001, 66, 739; c)
(4S,5S)-5-(Benzyloxy)undeca-1,10-dien-4-ol (5):
20
[α]D + 10.75 (c = 0.37, CHCl3); IR (neat): υmax
3430, 2920, 1624, 1460, 734 cm-1; 1H NMR
(CDCl3, 300 MHz): δ 7.34 - 7.23 (m, 5H), 5.88 -
5.68 (m, 2H), 5.15 - 4.89 (m, 4H), 4.55 (dd, J =
11.3, 4.5 Hz, 2H), 3.78 - 3.72 (m, 1H), 3.37 - 3.31
(m, 1H), 2.28 - 2.20 (m, 2H), 2.08 - 1.99 (m, 2H),
1.66 – 1.28 (m, 6H); 13C NMR (CDCl3, 75 MHz): δ
138.8, 138.4, 135.0, 128.4, 127.8, 127.6, 117.6,
114.3, 81.6, 72.1, 71.2, 36.8, 33.6, 29.0, 28.9, 25.0;
ESI-MS: m/z: 297 (M+Na).
(E)-Ethyl 3-((4R,5R)-5-((benzyloxy)methyl)-2,2-
dimethyl-1,3-dioxolan-4-yl)acrylate (16):

5
20
[α]D + 1.56 (c = 1.66, CHCl3); IR (neat): υmax 2930,
1.37 (s, 3H), 1.32 (s, 3H), 1.46 - 1.19 (m, 22H), 0.88 (t,
1725, 1648, 776 cm-1; H NMR (CDCl3, 300 MHz): δ
J = 6.9 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 139.0,
128.2, 127.8, 127.3, 109.2, 82.2, 81.5, 79.9, 78.2, 72.8,
67.6, 31.9, 30.9, 29.7, 29.6, 29.6×3, 29.3, 29.1, 28.3,
27.3, 26.7, 25.6, 25.3, 22.6, 14.1; ESI-MS: m/z: 461
(M+H), 478 (M+NH4); HRMS (C29H48O4Na: calcd
483.34448; found: 483.34182.
1
7.40 - 7.27 (m, 5H), 6.90 (dd, J = 15.6, 5.4 Hz, 1H), 6.09
(dd, J = 15.4, 1.1 Hz, 1H), 4.60 (s, 2H), 4.46 - 4.40 (m,
1H), 4.21 (q, J = 7.1 Hz, 2H), 4.01 - 3.93 (m, 1H), 3.63
(d, J = 4.7 Hz, 2H), 1.46 (s, 3H), 1.44 (s, 3H), 1.29 (t, J =
7.1 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 165.8, 143.9,
137.5, 128.2, 127.6, 127.5, 122.3, 110.0, 79.3, 77.2, 73.4,
69.1, 60.0, 26.7, 26.5, 14.0; ESI-MS: m/z: 321 (M+H),
(2S,4S,6R)-2-((S)-1-(Benzyloxy)hept-6-enyl)-6-
((2R,5R)-5-((R)-1-(benzyloxy)tridecyl)-
343
(M+Na).
(E)-Ethyl-5-((4R,5R)-5-
((benzyloxy)methyl)-2,2-dimethyl-1,3-dioxolan-4-
tetrahydrofuran-2-yl)-tetrahydro-2H-pyran-4-ol (28):
[α]D20 + 2.2 (c = 0.36, CHCl3); IR (neat): υmax 3434, 2926,
2851, 1628, 1463, 726 cm-1; 1H NMR (CDCl3, 300
MHz): δ 7.39 - 7.14 (m, 10H), 5.77 - 5.63 (m, 1H), 4.97 -
4.82 (m, 2H), 4.66 (t, J = 11.5 Hz, 2H), 4.52 (t, J = 12.4
Hz, 2H), 4.14 - 3.99 (m, 2H), 3.97 - 3.89 (m, 1H), 3.82 -
3.69 (m, 1H), 3.48 - 3.22 (m, 3H), 2.02 - 1.78 (m, 4H),
1.67 - 1.49 (m, 4H), 1.44 - 1.08 (m, 30H), 0.81 (t, J = 6.7
Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 139.1, 138.88,
138.82, 132.1, 128.17, 128.12, 127.8, 127.4, 127.2,
114.2, 82.09, 82.0, 80.9, 80.7, 80.6, 77.5, 72.8, 72.6,
68.4, 36.8, 36.1, 34.5, 33.6, 33.5, 31.8, 30.7, 29.9, 29.7,
29.5, 29.2, 28.8, 28.3, 27.5, 27.4, 25.6, 25.18, 25.13,
22.6, 14.0; ESI-MS: m/z: 663 (M+H); HRMS
(C43H66O5Na): calcd 685.48025; found: 685.47833.
(2S,6R)-2-((S)-1-(Benzyloxy)hept-6-enyl)-6-((2R,5R)-
5-((R)-1-(benzyloxy)tridecyl)-tetrahydrofuran-2-yl)-
20
yl)pent-2-enoate (19): [α]D + 12.83 (c = 2.26, CHCl3);
IR (neat): υmax 2915, 1728, 1646, 768 cm-1; 1H NMR
(CDCl3, 300 MHz): δ 7.38 -7.29 (m, 5H), 6.97 (dt, J =
15.6, 6.9 Hz, 1H), 5.83 (dt, J = 15.6, 1.5 Hz, 1H), 4.58 (s,
2H), 4.18 (q, J = 7.1 Hz, 2H), 3.88 - 3.78 (m, 2H), 3.62 -
3.48 (m, 2H), 2.47 - 2.23 (m, 2H), 1.80 - 1.60 (m, 2H),
1.41 (s, 3H), 1.39 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H); 13C
NMR (CDCl3, 75 MHz): δ 166.1, 143.0, 138.4, 128.3,
127.7, 127.6, 121.8, 108.8, 79.6, 77.9, 73.5, 70.3, 59.9,
31.6, 28.6, 27.3, 27.0, 14.3; ESI-MS: m/z: 349 (M+H),
371 (M+Na).
((2S,3S)-3-(2-((4R,5R)-5-((Benzyloxy)methyl)-2,2-
dimethyl-1,3-dioxolan-4-yl)ethyl)
oxiran-2-
20
1
yl)methanol (21): [α]D + 1.67 (c = 0.6, CHCl3); H
NMR (CDCl3, 400 MHz): δ 7.33 - 7.22 (m, 5H), 4.55 (s,
2H), 3.83 - 3.73 (m, 2H), 3.62 - 3.54 (m, 2H), 3.52 - 3.48
(m, 1H), 2.93 - 2.88 (m, 2H), 2.87 - 2.83 (m, 1H), 1.87 -
1.59 (m, 4H), 1.37 (s, 3H), 1,35 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 137.8, 128.4, 127.7, 127.6, 108.9,
79.8, 77.7, 73.5, 70.4, 61.6, 58.2, 55.3, 29.1, 27.8, 27.2,
26.9; ESI-MS: m/z: 322 (M) 345 (M+Na).
20
tetrahydro-2H-pyran (2): [α]D + 18.0 (c = 0.1,
CHCl3); IR (neat): υmax 2916, 2843, 1621, 1469, 739 cm-
1
1; H NMR (CDCl3, 500 MHz): δ 7.31 - 7.14 (m, 10H),
5.74 - 5.66 (m, 1H), 4.92 - 4.82 (m, 2H), 4.67 (t, J = 11.6
Hz, 2H), 4.52 (dd, J = 19.8, 11.6 Hz, 2H), 4.06 - 4.00 (m,
1H), 3.91 - 3.86 (m, 1H), 3.44 - 3.39 (m, 1H), 3.35 - 3.30
(m, 1H), 3.29 - 3.27 (m, 2H), 1.97 - 1.69 (m, 4H), 1.62 -
1.32 (m, 16H), 1.30 - 1.05 (m, 20H), 0.81 (t, J = 7.0 Hz,
3H); 13C NMR (CDCl3, 75 MHz): δ 139.28, 139.2, 139.0,
128.18, 128.13, 127.9, 127.8, 127.3, 127.2, 114.1, 81.9,
81.4, 81.2, 80.1, 79.9, 72.9, 72.6, 68.8, 34.0, 33.7, 31.9,
30.7, 30.0, 29.7, 29.6, 29.4, 29.2, 29.1, 28.9, 28.3, 27.5,
27.3,28.0, 27.2, 26.4, 25.7, 25.3, 22.7, 14.1; ESI-MS:
m/z: 664 (M+NH4)..
(R)-2-(Benzyloxy)-1-((2R,5R)-tetrahydro-5-((S)-2,2-
dimethyl-1,3-dioxolan-4-yl) furan-2-yl)ethanol (22):
[α]D _5.63 (c = 0.8, CHCl3); H NMR (CDCl3, 400
MHz): δ 7.32 - 7.22 (m, 5H), 4.53 (s, 2H), 4.04 - 3.96 (m,
2H), 3.93 - 3.86 (m, 2H), 3.78 (dd, J = 8.0, 5.0 Hz, 1H),
3.61 (q, J = 5.0 Hz, 1H), 3.50 - 3.44 (m, 2H), 2.14 -2.07
(m, 1H), 2.00 - 1.94 (m, 1H), 1.93 - 1.89 (m, 1H), 1.87 -
1.75 (m, 1H), 1.37 (s, 3H), 1.31 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 137.8, 128.1, 127.5×2, 109.0, 79.9,
79.7, 77.6, 73.2, 72.4, 71.6, 67.1, 28.6, 27.6, 26.6, 25.1;
ESI-MS: m/z: 322 (M), 345 (M+Na); HRMS
(C18H26O5Na): calcd 345.16725; found: 345.16599.
20
1
(R)-1-((2R,5R)-Tetrahydro-5-((S)-2,2-dimethyl-1,3-
dioxolan-4-yl)furan-2-yl) tridecan-1-ol (26) [α]D
20
+
3.42 (c = 0.6, CHCl3); IR (Neat): υmax 3450, 2922, 1472,
1
768 cm-1; H NMR (CDCl3, 300 MHz): δ 4.04 (dd, J =
8.3, 6.0 Hz, 1H), 3.94 - 3.70 (m, 4H), 3.31 (dd, J = 11.3,
6.0 Hz, 1H), 2.14 - 2.06 (m, 1H), 2.03 - 1.92 (m, 1H),
1.84 - 1.76 (m, 1H), 1.69 - 1.59 (m, 1H), 1.37 (s, 3H),
1.32 (s, 3H), 1.35 - 1.32 (m, 22H), 0.89 (t, J = 6.7 Hz,
3H); 13C NMR (CDCl3, 75 MHz): δ 109.2, 82.9, 79.7,
77.8, 74.0, 67.2, 33.3, 31.9, 29.5×2, 29.2×2, 29.0, 28.6,
28.2, 28.0, 27.2, 26.5, 25.5, 25.2, 22.6, 14.0; ESI-MS:
m/z: 393 (M+Na); HRMS (C22H42O4Na): calcd
393.29753; found: 393.29627. (S)-4-((2R,5R)-5-((R)-1-
(Benzyloxy)tridecyl)-tetrahydrofuran-2-yl)-2,2-
20
dimethyl-1,3-dioxolane (27): [α]D + 6.40 (c = 0.17,
1
CHCl3); H NMR (CDCl3, 300 MHz): δ 7.33 - 7.18 (m,
5H), 4.61 (dd, J = 6.2, 11.7 Hz, 2H), 4.11 - 3.97 (m, 3H),
3.93 - 3.79 (m, 2H), 3.24 (dd, J = 10.5, 5.0 Hz, 1H), 2.12
- 2.04 (m, 1H), 1.99 - 1.88 (m, 1H), 1.80 - 1.58 (m, 2H),