First Total Synthesis of (3 R,4 S)-4-Hydroxylasiodiplodin: A Facile and Stereoselective Approach

Article abstract of DOI:10.1055/s-0032-1317805

A first total synthesis of (3R,4S)-4-hydroxylasiodiplodin is described starting from methyl acetoacetate and a commonly available carbohydrate, d-mannitol, which is regularly used in organic synthesis. The facile and stereoselective approach involves the

Full text of DOI:10.1055/s-0032-1317805

LETTER
▌1117
letter
First Total Synthesis of (3R,4S)-4-Hydroxylasiodiplodin: A Facile and Stereo-
selective Approach
Total Synthesis of (3R,4S)-4-Hydroxylasiodiplodin
Sheshurao Bujaranipalli, Gyan Chander Eppa, Saibal Das*
Natural Products Chemistry Division, CSIR Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, AP, India
Fax +91(40)27160512; E-mail: saibal@iict.res.in
Received: 05.03.2013; Accepted: 19.03.2013
As outlined below, the retrosynthetic approach (Scheme
Abstract: A first total synthesis of (3R,4S)-4-hydroxylasiodiplodin
1) suggests that the construction of the 12-membered
is described starting from methyl acetoacetate and a commonly
macrolide could be obtained using a RCM approach of
available carbohydrate, D-mannitol, which is regularly used in or-
compound 2 which could be envisaged from esterification
of compound 3 with 4. Finally, compounds 3 and 4 may
be prepared from easily available methyl acetoacetate 5
and D-mannitol, respectively, using well-established pro-
tocols in good yields.
ganic synthesis. The facile and stereoselective approach involves
the Barbier allylation and a ring-closing metathesis as key steps.
Key words: Hydroxylasiodiplodin, Barbier allylation, metathesis,
carbohydrate, total synthesis, natural product
esterification
A number of naturally occurring orsellinic acid (2,4-dihy-
droxy-6-methyl benzoic acid)-type macrolides are known
in the literature, including radicicol,1 zearalenone,2 lasio-
diplodin,3 resorcylide,4 and have been shown to possess a
variety of interesting biological properties.5 Many among
these lasiodiplodins are unique fungal metabolites of
lasiodiplodia theobromae that acts in the inhibition of
prostaglandin biosynthesis,6 potent antileukemic activi-
ty,7 cytotoxic,8 potent nonsteroidal antagonist of the min-
eralocorticoid receptor (MR),9 antimicrobial activity,10
potato microtuber inducing activities, plant-gowth
inhibitor3 and also acts as a Hill reaction inhibitor.11 In
particular, (3R,4S)-4-hydroxylasiodiplodin (1) is a 12-
membered macrolide (Figure 1) isolated from IFO
3105912 and was found to show strong potato microtuber
inducing activity at a concentration of 10–4 M.
OMe
O
OMe
O
OH
OH
O
O
HO
HO
1
2
RCM approach
OMe
O
OH
OH
+
OH
HO
3
4
O
O
D-mannitol
OMe
O
OMe
OH
5
O
Scheme 1 Retrosynthesis for compound 1
HO
To begin our synthesis, aromatic subunit 3 was construct-
ed (Scheme 2) starting from methyl acetoacetate which
was transformed into the desired aromatic ester14 6 in one
pot in 50% yield. Then, regioselective protection of the 4-
hydroxy group as its ether 7 was achieved using MOMCl
1
Figure 1 (3R,4S)-4-Hydroxylasiodiplodin (1)
Owing to the growing importance of this family of com-
pounds and our ongoing interest in the total synthesis of
biologically active natural products,13 we report the first
total synthesis of (3R,4S)-4-hydroxylasiodiplodin (1) that
involves a simple strategy using Barbier allylation and
ring-closing metathesis (RCM) as the key steps starting
from very common and inexpensive starting materials:
methyl acetoacetate and D-mannitol.
1
in the presence of DIPEA in 85% yield. The H NMR
spectrum shows a singlet at δ = 11.65 ppm that indicates
the presence of a hydroxyl group ortho to the internal keto
functionality, suggesting that the protection of only the 4-
hydroxy group as its MOM ether was attained. Compound
7 was then treated with dimethyl sulfate to obtain 2-me-
thoxy compound 8 in 80% yield.15 Lithiation of com-
pound 8 at the benzylic position with LDA at –78 °C
followed by reaction with homoallylbromide afforded the
expected compound 9 in 62% yield, which was then
saponified to furnish the desired acid 1016 in 86% yield.
SYNLETT 2013, 24, 1117–1120
Advanced online publication: 12.04.2013
DOI: 10.1055/s-0032-1317805; Art ID: ST-2013-D0201-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6

1118
S. Bujaranipalli et al.
LETTER
Having compound 10 in hand, the synthesis towards com-
pound 4 was focused upon (Scheme 4). D-mannitol, a car-
bohydrate precursor was deployed for the preparation of
enantiomerically pure (R)-2,3-O-cyclohexylidine glycer-
aldehyde (11) using a literature procedure.18 Then com-
pound 11 was subjected to Barbier allylation conditions
(Zn, allyl bromide and aq NH4Cl) to obtain the anti-
homoallylic alcohol 12 in 91% yield with 94% de.
OH
O
O
O
a
OMe
OMe
b
OMe
HO
5
6
OH
O
O
O
d
c
OMe
OMe
OMe
MOMO
MOMO
OH
8
7
ref. 18
OMe
O
a
OMe
O
O
O
D-mannitol
O
O
e
OH
MOMO
MOMO
11
12
OBn
9
10
OBn
Scheme 2 Reagents and conditions: (a) NaH, n-BuLi, 0 °C to –78 °C
to r.t., 12 h, reflux, 24 h, 50%; (b) MOMCl, DIEPA, CH2Cl2, 0 °C to
r.t., 3 h, 85%; (c) K2CO3, Me2SO4, dry acetone, reflux, 12 h, 80%; (d)
LDA, homoallyl bromide, –78 °C, 30 min, 62%; (e) KOH, (MeOH–
H2O, 1:1), reflux, 2 d, then 1 M HCl, 86%.
c
b
O
HO
O
OH
14
13
OBn
OBn
We had initially protected the 4-hydroxy group in com-
pound 6 as its benzyl ether using benzyl bromide in the
presence of K2CO3 to afford compound 7a in 60% yield,
followed by methylation on the 2-hydroxy group using di-
methyl sulfate to give 8a in 82% yield (Scheme 3). In
compound 8a two benzylic positions are found: 1) one
ortho to the ester group, and 2) a second one that is part of
the benzyl ether protecting group. Since toluene deriva-
tives with heteroatom-containing substituents in the ortho
position undergo site-selective benzylic lithiation for fur-
ther functionalization,17 we expected lithiation to occur at
one benzylic position and not the other. Unfortunately,
lithiation did not occur at either of the benzylic positions
with LDA at –78 °C and only starting material was recov-
ered. Hence, the search for other protecting groups came
into play. The protecting groups must be stable under ba-
sic and mild acidic conditions and will be used under sa-
ponification conditions in the later stage of the approach.
Therefore, we opted for methoxymethyl ether as the pro-
tecting group which is stable under the above-mentioned
conditions and serves the purpose.
e
d
O
OH
16
15
Scheme 4 Reagents and conditions: (a) Zn, allyl bromide, aq NH4Cl,
0 °C, 4 h, 91%; (b) NaH, BnBr, THF, 0 °C to r.t., 6 h, 93%; (c) 60%
AcOH in H2O, r.t., overnight, 86%; (d) TPP, DEAD, CHCl3, reflux,
12 h, 85%; (e) LAH, THF, 0 °C to r.t., 6 h, 89%.
The diastereomers were easily separated by column chro-
matography,19 and homoallylic alcohol 12 was protected
using benzyl bromide in the presence of NaH in THF to
afford the corresponding benzyl ether 13 in 93% yield.
The cyclohexylidine protection was then removed using
60% AcOH in water to afford the desired 1,2-diol 14 in
86% yield which was converted into the epoxide 15 under
Mitsunobu conditions.20 Afterwards reductive opening of
the epoxide 15 with LAH furnished the secondary alcohol
16 in 89% yield.
The next steps were to couple the two intermediate com-
pounds 10 and 16 and to construct the 12-membered ring
(Scheme 5). Accordingly, the ester 17 was obtained under
stoichiometric conditions via an acyl activation21 of the
acid intermediate 10 using DCC and DMAP at room tem-
perature in 62% yield, followed by treatment with 5 mol%
of Grubbs second-generation catalyst under dilute
conditions22 to afford the desired lactone 18 in 81% yield
with a E/Z ratio of 7:3 based on HPLC analysis observa-
tions, which upon treatment with 10% palladium on car-
bon provided 19 in 87% yield. Finally, deprotection of
MOM ether with aqueous HCl in methanol afforded the
target compound 1 in 91% yield. The spectral data of thus
OH
O
b
a
OMe
6
BnO
7a
OMe
O
OMe
O
c
OMe
OMe
BnO
BnO
9a
8a
Scheme 3 Reagents and conditions: (a) BnBr, K2CO3, dry acetone, synthesized target compound was in agreement with the
natural product12,23 and was further confirmed by NOE
experiment under irradiation of the proton present at posi-
reflux, 12 h, 60%; (b) K2CO3, Me2SO4, dry acetone, reflux, 12 h,
82%; (c) LDA, homoallyl bromide, –78 °C, 30 min.
tion 4. Enhancement of CH3 protons was observed, sug-
Synlett 2013, 24, 1117–1120
© Georg Thieme Verlag Stuttgart · New York

LETTER
Total Synthesis of (3R,4S)-4-Hydroxylasiodiplodin
1119
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Prod. 2011, 74, 1126.
gesting they are cofacial, and no enhancement of the
proton present at position 3 indicated their anti relation-
ship as well.
OMe
O
a
b
O
10 + 16
OBn
OMe
(6) Xin-Sheng, Y.; Ebizuka, Y.; Noguchi, H.; Kiuchi, F.; Litaka,
Y.; Sankawa, U.; Seto, H. Tetrahedron Lett. 1983, 24, 2407.
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Vieira, P. C.; Ferndes, J. B.; Silva, M. F. G. F.; Müller, M.
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4217.
MOMO
17
OMe
O
O
OBn
OH
O
O
c
MOMO
MOMO
18
19
OMe
O
3
OH
O
d
4
HO
1
(12) Yang, Q.; Asai, M.; Matsuura, H.; Yoshihara, T.
Phytochemistry 2000, 54, 489.
Scheme 5 Reagents and conditions: (a) DCC, DMAP, CH2Cl2, 0 °C
to r.t., 5 h, 62%; (b) Grubbs II catalyst (5 mol%), CH2Cl2, reflux, 12
h, 81%; (c) H2, 10% Pd/C, EtOAc, 6 h, 87%; (d) 1 N HCl–MeOH
(1:1), r.t., 24 h, 91%.
(13) (a) Yadav, J. S.; Das, S.; Mishra, A. K. Tetrahedron:
Asymmetry 2010, 21, 2443. (b) Das, S.; Mishra, A. K.;
Kumar, A.; Ghamdi, A. A. K. A.; Yadav, J. S. Carbohydr.
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Tetrahedron 2007, 63, 7053.
(17) For a general review of benzylic anions, see: Clark, R. D.;
Jahangin, A. Org. React. 1995, 47, 1.
In conclusion, the first total synthesis of (3R,4S)-4-hydox-
ylasiodiplodin has been accomplished by employing
Barbier allylation and ring-closing metathesis as the key
steps. This method can be conveniently utilized for the
synthesis of different other resorcylic macrolides towards
the development of such class of compounds.
Acknowledgment
(18) Chattopadhyay, A.; Mamdapur, V. R. J. Org. Chem. 1995,
60, 585.
(19) Chattopadhyay, A. J. Org. Chem. 1996, 61, 6104.
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Tetrahedron Lett. 2000, 41, 1959.
B.S. thanks UGC and E.G.C. thanks CSIR, New Delhi, India for fel-
lowships. Authors thank CSIR, New Delhi for financial supports
through Project ORIGIN under 12th Five Year Plan.
(21) Selles, P.; Lett, R. Tetrahedron Lett. 2002, 43, 4621.
(22) Fürstner, A.; Kindler, N. Tetrahedron Lett. 1996, 37, 7005.
(23) Spectral Data for Representative Compounds
Methyl 2-Hydroxy-4-(methoxymethoxy)-6-methyl-
benzoate(7)
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
Mp 55–58 °C. IR (KBr): 2956, 2855, 2831, 1726, 1657,
1618, 1579, 1446, 1422, 1369, 1324, 1261, 1215, 1152,
1111, 1080, 1062, 1020, 942, 845, 803, 770, 700, 673, 606,
578, 528 cm–1. 1H NMR (300 MHz, CDCl3): δ = 11.65 (s, 1
H), 6.47 (d, J = 3.0 Hz, 1 H), 6.36 (s, J = 2.3 Hz, 1 H), 5.15
(s, 2 H), 3.90 (s, 3 H), 3.45 (s, 3 H), 2.48 (s, 3 H). 13C NMR
(75 MHz, CDCl3): δ = 172.1, 165.2, 161.4, 143.3, 111.8,
101.5, 93.8, 56.3, 51.9, 29.7, 24.4. ESI-MS: m/z = 227 [M +
H]+. ESI-HRMS: m/z calcd for C11H18O6Na: 269.1001;
found: 269.0992.
References and Notes
(1) Nozawa, K.; Nakajima, S. J. Nat. Prod. 1979, 42, 374.
(2) (a) Stob, M.; Baldwin, R. S.; Tuite, J.; Andrews, F. N.;
Gillette, K. G. Nature (London) 1962, 196, 1318. (b) Urry,
W. H.; Wehrmeister, H. L.; Hodge, E. B.; Hidy, P. H.
Tetrahedron Lett. 1966, 7, 3109.
(3) (a) Aldridge, D. C.; Galt, S.; Giles, D.; Turner, W. B. J.
Chem. Soc. C 1971, 1623. (b) Li, P.; Takahashi, K.;
Matsuura, H.; Yoshihara, T. Biosci. Biotechnol. Biochem.
2005, 69, 1610.
(4) Oyama, H.; Sassa, T.; Ikeda, M. Agric. Biol. Chem. 1978, 42,
2407.
(5) (a) Ayer, W. A.; Lee, S. P.; Tsuneda, A.; Hiratsuka, Y. Can.
J. Microbiol. 1980, 26, 776. (b) Matsuura, H.; Nakamori, K.;
Omer, E. A.; Hatakeyama, C.; Yoshihara, T.; Ichihara, A.
Phytochemistry 1998, 49, 579. (c) Isaka, M.;
Methyl 2-Methoxy-4-(methoxymethoxy)-6-methyl-
benzoate (8)
IR (neat): 2944, 2846, 1727, 1602, 1585, 1459, 1434, 1321,
1268, 1231, 1189, 1149, 1096, 1078, 1026, 962, 928, 836,
814, 773 cm–1. 1H NMR (300 MHz, CDCl3): δ = 6.47 (d,
J = 1.7 Hz, 1 H), 6.45 (d, J = 2.0 Hz, 1 H), 5.17 (s, 2 H), 3.88
(s, 3 H), 3.80 (s, 3 H), 3.48 (s,3 H), 2.27 (s, 3 H). 13C NMR
(75 MHz, CDCl3): δ = 168.5, 158.9, 157.9, 138.0, 117.3,
Suyarnsestakorn, C.; Tanticharoen, M. J. Org. Chem. 2002,
67, 1561. (d) Hellwig, V.; Mayer-Bartschmid, A.; Müller,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1117–1120

1120
S. Bujaranipalli et al.
LETTER
109.2, 94.2, 97.7, 55.9, 55.8, 51.9, 19.7. ESI-MS: m/z = 241
[M + H]+. ESI-HRMS: m/z calcd for C12H16O5Na: 263.0890;
found: 263.0894.
Methyl 2-Methoxy-4-(methoxymethoxy)-6-(pent-4-
enyl)benzoate (9)
IR (neat): 2951, 3004, 2907, 2838, 1739, 1709, 1615, 1577,
1431, 1297, 1219, 1137, 1103, 1037, 966, 930, 823, 772, 640
cm–1. 1H NMR (300 MHz, CDCl3): δ = 6.48 (m, 2 H), 5.89–
5.71 (m, 1 H), 5.17 (s, 2 H), 5.07–4.87 (m, 2 H), 3.88 (s, 3
H), 3.47 (s, 3 H), 2.62–2.50 (m, 2 H), 2.15–2.07 (ABq,
J = 14.0, 6.8 Hz, 2 H), 1.74–1.62 (m, 2 H). 13C NMR (75
MHz, CDCl3): δ = 168.7, 158.9, 157.8, 142.5, 138.3, 125.5,
114.8, 108.4, 97.8, 94.3, 56.0, 55.9, 33.4, 33.1, 30.2. ESI-
MS: m/z = 295 [M + H]+.
NMR (300 MHz, CDCl3): δ = 7.38–7.28 (m, 5 H), 6.49 (d,
J = 2.1 Hz, 1 H), 6.45 (d, J = 2.1 Hz, 1 H), 5.98–5.70 (m, 2
H), 5.45–5.22 (m, 2 H), 5.17 (s, 2 H), 5.12–4.91 (m, 3 H),
4.63 (m, 2 H), 3.81–3.74 (m, 3 H), 3.69–3.62 (m, 1 H), 3.48
(s, 3 H), 2.64–2.54 (m, 2 H), 2.44–2.35 (m, 2 H), 2.06 (ABq,
J = 7.0, 14.1 Hz, 2 H), 1.73–1.64 (m, 2 H), 1.38 (d, J = 6.4
Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 167.6, 158.8,
157.7, 142.2, 138.3, 134.6, 128.2, 127.7, 127.4, 117.3,
108.3, 97.7, 94.3, 80.4, 72.6, 72.5, 56.0, 55.6, 35.5, 33.5,
33.0, 30.3, 15.0. ESI-MS: m/z = 491 [M + Na]+. ESI-HRMS:
m/z calcd for C28H36O6Na: 491.2404; found: 491.2405.
(3R,4S)-4-(Benzyloxy)-14-methoxy-12-
(methoxymethoxy)-3-methyl-3,4,5,8,9,10-hexahydro-
1H-benzo[c][1]oxacyclododecin-1-one (18)
2-Methoxy-4-(methoxymethoxy)-6-(pent-4-enyl)benzoic
Acid (10)
Mp 86–90 °C. [α]D30 32 (c 1, CHCl3). IR (KBr): 2925, 2854,
1724, 1604, 1586, 1456, 1373, 1346, 1311, 1261, 1230,
1212, 1191, 1149, 1091, 1070, 1017, 964, 932, 830, 738, 698
cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.40–7.27 (m, 5 H),
6.51 (d, J = 1.9 Hz, 1 H), 6.42 (d, J = 1.9 Hz, 1 H), 5.70–5.51
(m, 1 H), 5.42–5.24 (m, 2 H), 5.16 (d, J = 1.3 Hz, 2 H), 4.82–
4.44 (m, 2 H), 3.75 (s, 3 H), 3.62–3.53 (m, 1 H), 3.50 (s, 3
H), 2.62–2.49 (m, 2 H), 2.32–2.19 (m, 2 H), 2.15–1.96 (m, 2
H), 1.91–1.77 (m, 2 H), 1.43 (d, J = 5.9 Hz, 3 H). 13C NMR
(75 MHz, CDCl3): δ = 167.4, 158.8, 157.2, 142.1, 138.3,
132.6, 128.7, 128.4, 128.3, 127.7, 127.6, 124.8, 108.3,
107.3, 97.7, 94.4, 80.5, 73.6, 71.3, 55.9, 56.1, 30.9, 31.8,
29.7, 29.5, 17.7. ESI-MS: m/z = 463 [M + Na]+. ESI-HRMS:
m/z calcd for C26H32O6Na: 463.2091; found: 463.2091.
(3R,4S)-4-Hydroxy-14-(methoxymethoxy)-3-methyl-
3,4,5,6,7,8,9,10-octahydro-1H-benzo[c][1]oxacyclo-
dodecin-1-one (19)
IR (neat): 3076, 2932, 1697, 1603, 1460, 1425, 1297, 1218,
1193, 1151, 1113, 1081, 1021, 918, 837, 772 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 6.58 (d, J = 1.8 Hz, 1 H), 6.53 (d,
J = 2.1 Hz 1 H), 5.93–5.76 (m, 1 H), 5.50–5.40 (m, 1 H),
5.21 (s, 2 H), 5.08–4.92 (m, 1 H), 3.93 (s, 3 H), 3.49 (s, 3 H),
2.92–2.80 (m, 2 H), 2.12 (ABq, J = 14.2, 7.17 Hz, 2 H),
1.79–1.64 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 171.8,
159.4, 158.4, 144.4, 138.3, 115.3, 114.7, 109.3, 97.8, 94.1,
55.9, 33.5, 33.4, 30.3. ESI-MS: m/z = 281 [M + H]+. ESI-
HRMS: m/z calcd for C15H21O5Na: 281.1384; found:
281.1369.
(R)-2-[(S)-1-(Benzyloxy)but-3-enyl]oxirane (15)
[α]D30 +5.40 (c 1, CHCl3). IR (neat): 3032, 3065, 2989, 2925,
2867, 1955, 1824, 1642, 1495, 1454, 1434, 1391, 1344,
1306, 1252, 1207, 1159, 1098, 1074, 1028, 995, 917, 851,
739, 698, 609, 2982, 2933, 1647, 1608, 1574, 1445, 1376,
1357, 1319, 1257, 1211, 1159, 1103, 1034, 967, 864, 757
cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.32–7.20 (m, 5 H),
5.94–5.82 (m, 1 H), 5.17–5.06 (m, 2 H), 4.62–4.52 (m, 2 H),
3.32–3.28 (m, 1 H), 2.92–2.88 (m, 1 H), 2.73–2.70 (m, 1 H),
2.68–2.65 (m, 1 H), 2.47–2.35 (m, 2 H). 13C NMR (75 MHz,
CDCl3): δ = 138.3, 133.9, 128.3, 127.6, 117.4, 77.7, 72.1,
53.1, 45.6, 37.2. ESI-MS: m/z = 227[M + Na]+. ESI-HRMS:
m/z calcd for C13H16O2Na: 227.1402; found: 227.1402.
(2R,3S)-3-(Benzyloxy)hex-5-en-2-ol (16)
Mp 105–107 °C. [α]D30 +7(c 1, CHCl3). IR (KBr): 3422,
2950, 2853, 2923, 1718, 1604, 1587, 1462, 1377, 1265,
1218, 1150, 1088, 1023, 771, 722 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 6.47 (m, 2 H), 5.17 (s, 2 H), 5.05–4.84 (m, 1 H),
3.78–3.80 (m, 4 H), 3.48 (s, 3 H), 2.83–2.69 (m, 1 H), 2.62–
2.51 (m, 1 H), 1.93–1.83 (m, 1 H), 1.74–1.56 (m, 5 H), 1.48
(d, J = 6.0 Hz, 3 H), 1.45–1.36 (m, 4 H). 13C NMR (75 MHz,
CDCl3): δ = 168.3, 158.9, 157.6, 142.6, 118.4, 108.7, 97.7,
94.3, 74.3, 73.9, 56.1, 55.9, 33.6, 31.9, 29.9, 25.9, 24.8, 21.4,
17.9. ESI-MS: m/z = 375 [M + Na]+. ESI-HRMS: m/z calcd
for C19H28O6Na: 375.1778; found: 375.1776.
[α]D30 +3.8 (c 0.3, CHCl3). IR (neat): 3432, 3070, 3031,
2977, 2931, 2874, 1718, 1641, 1496, 1453, 1396, 1370,
1258, 1215, 1092, 1070, 1028,996, 913, 772, 738, 698 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.36–7.20 (m, 5 H), 5.96–
5.76 (m, 1 H), 5.18–5.05 (m, 2 H), 4.65 (m, 2 H), 3.98–3.89
(m, 1 H), 3.46–3.39 (m, 1 H), 2.48–2.37 (m, 1 H), 2.33–2.23
(m, 1 H), 1.18 (d, J = 6.6 Hz, 3 H). 13C NMR (75 MHz,
CDCl3): δ = 138.4, 135.1, 127.7, 128.4, 127.8, 116.9, 82.4,
72.1, 68.2, 34.0, 17.8. ESI-MS: m/z = 229 [M + Na]+. ESI-
HRMS: m/z calcd for C13H18O2Na: 229.1199; found:
229.1199.
(2R,3S)-3-(Benzyloxy)hex-5-en-2-yl 2-Methoxy-4-
(methoxymethoxy)-6-(pent-4-en-1-yl)benzoate (17)
[α]D30 –7.0 (c 0.3, CHCl3). IR (neat): 3073, 2927, 2855,
1725, 1640, 1604, 1588, 1458, 1426, 1317, 1261, 1216,
1191, 1150, 1085, 1023, 966, 917, 838, 772, 698 cm–1. 1H
(3R,4S)-4-Hydoxylasiodiplodin (1)
Mp 213–215 °C. [α]D30 +3.5 (c 0.7, MeOH). IR (KBr): 3355,
2924, 2853, 1691, 1603, 1462, 1263, 1219, 1162, 1093,
1026, 772 cm–1. 1H NMR (300 MHz, CDCl3): δ = 6.28 (d,
J = 2.0 Hz, 1 H), 6.23 (d, J = 2.0 Hz 1 H), 4.76–4.71 (m, 1
H), 3.75 (s, 3 H), 3.66–3.61 (m, 1 H), 2.68 (ddd, J = 13.9,
7.9, 3.9 Hz, 1 H), 2.51 (ABq, J = 12.9, 7.0 Hz, 1 H), 1.85–
1.78 (m, 1 H), 1.74–1.67 (m, 1 H), 1.67–1.58 (m, 2 H), 1.57–
1.50 (m, 2 H), 1.42 (d, J = 6.0 Hz, 3 H), 1.37–1.32 (m, 2 H),
1.31–1.27 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 170.5,
160.9, 159.5, 143.7, 117.4, 109.4, 97.9, 75.0, 74.9, 56.3,
31.4, 31.3, 31.2, 27.3, 25.6, 22.5, 18.5. ESI-MS: m/z = 331
[M + Na]+. ESI-HRMS: m/z calcd for C17H24O5Na:
331.1516; found: 331.1518.
Synlett 2013, 24, 1117–1120
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