Stereoselective Total Synthesis of Pectinolides A, C, and H

Article abstract of DOI:10.1002/hlca.201500110

A simple and straightforward stereoselective total synthesis of Pectinolides A, C, and H is described. The synthesis has been started from commercially available (+)-diethyl l-tartrate and involves Ohira-Bestmann reaction, Corey-Bakshi-Shibata (CBS) reduction, and Still-Gennari olefination as key steps.

Full text of DOI:10.1002/hlca.201500110

Helv. Chim. Acta 2016, 99, 247 – 254
247
FULL PAPER
Stereoselective Total Synthesis of Pectinolides A, C, and H
by Ramesh Saudagar Ghogare, Sachin Bibishan Wadavrao, and Akkirala Venkat Narsaiah*)
Organic and Biomolecular Chemistry Division, Indian Institute of Chemical Technology, Hyderabad, Telangana 500007, India
(phone: +91-40-27191608; fax: +91-40-27160387; e-mail: vnakkirala@iict.res.in)
A simple and straightforward stereoselective total synthesis of pectinolides A, C, and H is described. The synthesis has
been started from commercially available (+)-diethyl L-tartrate and involves Ohira–Bestmann reaction, Corey–Bakshi–Shibata
(CBS) reduction, and Still–Gennari olefination as key steps.
Keywords: Pectinolides, Unsaturated lactones, Oxidation, CBS Reduction, Still–Gennari olefination.
Results and Discussions
Introduction
As part of our regular research program in the synthesis
of biologically active molecules [7], herein, we report the
stereoselective total synthesis of pectinolides A, C, and
H, based on LiAlH4 reduction in p-methoxy benzylide-
neacetal, Ohira–Bestmann homologation reaction, cou-
pling of a terminal alkyne with pentanal, Corey–Bakshi–
Shibata (CBS) reduction, and cis-olefination using the
Still–Gennari reagent followed by cyclization.
On the basis of a strategy represented in the retrosyn-
thetic analysis outlined in Scheme 1, the synthesis was
started with commercially available (+)-diethyl L-tartrate
(5). The ester was reacted with p-methoxybenzaldehyde
dimethyl acetal in the presence of p-toluene sulfonic acid
(PTSA) in toluene at reflux to give the corresponding
p-methoxybenzylideneacetal diethyl ester 6 in 70% yield.
Thus, obtained acetal ester was reductively opened
with LiAlH4 in the presence of AlCl3 [8] to give (2S,3S)-
3-(4-methoxybenzyloxy)butane-1,2,4-triol 7 in 70% yield.
The regioselective protection of the 1,2-diol was carried
out using 2,2-dimethoxypropane [Me2C(OMe)2] in the
presence of PTSA in dry acetone at ꢀ60 °C to afford
compound 8 in 85% yield [9]. The primary alcohol in
compound 8 was oxidized to the aldehyde under Swern
conditions [10], and the latter was subjected to one car-
bon homologation using the Ohira–Bestmann reagent [11]
to afford the alkyne 9 in 75% yield.
Natural products containing an α,b-unsaturated lactone
(pyron) ring are exhibiting various pharmacological activi-
ties like antifungal, antitumor, antibacterial, cytotoxic,
cyclooxygenase, and phospholipase A inhibition. The
broad range of biological activities reported for this class
of compounds is a result of their inherent tendency to
acts as good Michael acceptors. The α,b-unsaturated lac-
tones are widely distributed in all parts of plants including
Lamiaceae, Lauraceae, Annonaceae, and Piperaceae fam-
ilies. The activity and structural fascination of naturally
occurring pyrone molecules has been the subject of
intense research [1] (Fig. 1).
Pectinolides A – C (1 – 3) [2] and H (4) [3] were iso-
lated from CHCl3 extracts of the Mexican medicinal plant
Hyptis pectinata, belonging to the Lamiaceae family,
which is used in the treatment of fever, antiseptics for
skin and eye infections, gastric disturbances [4], muscular
pain, rhinopharyngitis, and lung congestion [5]. Pectino-
lide A displayed antimicrobial activity against Staphylo-
coccus aureus and Bacillus subtilis in the concentration
range of 6.25 – 12.5 lg/ml. Pectinolides B and C were
active with an MIC of 12.5 – 25 lg/ml against B. sub-
tilis and a value of 100 lg/ml against S. aureus. Pectino-
lide H also displayed a significant antimicrobial activity
against two multidrug resistant strains of S. Aureus,
XU-212, which is highly resistant to tetracycline, and SA
1199 B, which is resistant to certain fluoroquinolones.
Pectinolides A – C exhibited significant cytotoxic activity
(ED50 < 4 lg/ml) against a variety of tumor cell lines.
The fascinating structural features and potential biological
activity of pectinolides A, C, and H attracted many syn-
thetic chemists and led to their synthesis via various
routes [6].
The alkyne 9 was coupled with n-pentanal in the pres-
ence of n-BuLi in dry THF at ꢀ78 °C to give the alkynol
10 as a diastereoisomeric mixture in 80% yield. To obtain
the required diastereoisomer, 10 was oxidized under
Swern condition to afford the corresponding alkynone 11
in 90% yield, which was subjected to stereoselective
reduction using (S)-2-methyl-CBS-oxazaborolidine and
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Helv. Chim. Acta 2016, 99, 247 – 254
Fig. 1. Structures of pectinolides.
Scheme 1. Retrosynthetic analysis of pectinolides A (1), C (3), and H (4).
BH3-DMS [12] at ꢀ40 °C to give alcohol 12 (major 1,4-diene-1,2-dicarbonitrile (DDQ) in CH2Cl2/H2O (20:1)
isomer) in 90% yield with 96% de.1).
Thus, newly created chiral alcohol was acetylated with
Ac2O in the presence of pyridine and a catalytic amount
solvent mixture at room temperature followed by cycliza-
tion in a single step in 85% yield.
The lactone 18 was subjected to deprotection of the silyl
of 4-(dimethylamino)pyridine (DMAP) in CH2Cl2 at 0 °C ether using tetrabutylammonium fluoride (TBAF) in THF to
to afford compound 13 in 92% yield. The deprotection of
the acetonide group was achieved by using 50% aq. solu-
give the secondary alcohol 19 in 90% yield, and the CꢁC
bond was reduced to the (Z)-olefin by using Pd/CaCO3
tion of TFA in CH2Cl2 to give diol 14 in 90% yield. Thus, (Lindlar catalyst) [15] in AcOEt to furnished the target mole-
afforded diol was converted to bis(silyl) ether 15 in 90% cule pectinolide C (3) in 98% yield. The observed optical
25
t
yield using BuMe2SiCl, pyridine and a catalytic amount rotation of the compound was ½aꢂD = 77.8 (c = 0.5, MeOH)
25
and the literature reports show ½aꢂD = 80.9 (c = 0.76,
of DMAP in CH2Cl2 at 0 °C. In the next step, the pri-
mary silyl ether was deprotected selectively in the pres-
25
MeOH) [3] and ½aꢂD = 72.4 (c = 0.5, MeOH) [6b]. Another
ence of camphor sulfonic acid (CSA) at 0 °C by using target molecule, pectinolide A (1) was obtained from pecti-
CH2Cl2/MeOH (3:1) solvent mixture to afford 16 in 80% nolide C (3) by acetylation with Ac2O in the presence of pyr-
yield (Scheme 2).
The primary alcohol was oxidized to the aldehyde (90% yield) as shown in the Scheme 3. The observed optical
idine and a catalytic amount of DMAP in CH2Cl2 at 0 °C
25
with Dess–Martin periodinane [13] and subjected to Still–
rotation of
25
1
was ½aꢂD = 190.2 (c = 0.5, MeOH)
Gennari olefination to get stereoselectively the cis-olefin {½aꢂD = 191.3 (c = 0.5, MeOH) [6b]}.
ester 17 in 88% yield [14]. The six-membered a,b-unsatu-
In a similar manner, the 5-membered a,b-unsaturated
rated d-lactone 18 was achieved from 17 by deprotection c-lactone 20 was achieved by deprotecting the silylether
of the PMB ether using 4,5-dichloro-3,6-dioxocyclohexa- from the (Z)-olefin ester 17 using TBAF in THF, fol-
lowed by cyclization in a single step to give the product
in 90% yield. For deprotection of the PMB ether, 20 was
treated with DDQ in CH2Cl2/H2O (20:1) mixture at room
temperature to give the alcohol 21 in 85% yield, which
1) Diastereomeric excess measured by reverse phase HPLC column XDB-
C18 (70:30 CH3CN/H2O, flow rate 1 ml/min, 200 nm), tR: 1.755 and 2.531.
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Scheme 2
a) p-MeOC6H4CH(OMe)2, p-TSA, toulene, reflux, 8 h, 70%; b) LiAlH4, AlCl3, THF, ꢀ30 °C -reflux, 3 h, 70%; c) 2,2-DMP [Me2C(OMe)2], ace-
tone, p-TSA, ꢀ60 °C,1 h, 85%; d) i) (COCl)2, DMSO, Et3N, ꢀ78 °C, 3 h, 90%; ii) dimethyl-1-diazo-2-oxopropylphosphonate, K2CO3, MeOH,
0 °C, 2 h, 72%; e) n-BuLi, n-pentanal, THF, ꢀ78 °C, 80%; f) (COCl)2, DMSO, Et3N, ꢀ78 °C, 3 h, 90%; g) (S)-2-methyl-CBS-oxazaborolidine
catalyst, THF, ꢀ40 °C, BH3ꢃDMS, 3 h, 90%; h) Ac2O, pyridine, DMAP, CH2Cl2, 0 °C, 30 min, 92%.; i) 50% TFA, CH2Cl2, 0 °C – r.t., 30 min,
90%; j) tBuMe2Si-Cl, pyridine, cat. 4-(dimethylamino)pyridine (DMAP), CH2Cl2, 0 °C, 1 h 90%; k) CH2Cl2/MeOH 3:1, (camphorsulfonic acid) CSA,
0 °C,1 h, 80%; l) i) Dess–Martin periodinane, NaHCO3, CH2Cl2, 0 °C, 1 h, 90%; ii) (F3CCH2O)2P(O)CH2CO2Me, NaH, THF, ꢀ78 °C, 1 h, 88%.
Scheme 3
a) DDQ, CH2Cl2/H2O 20:1, r.t., 2 h, 85%; b) TBAF, THF, 0 °C – r.t., 3 h, 90%; c) Lindlar’s catalyst, quinoline, AcOEt, r.t., 30 min, 98%; d)
Ac2O, pyridine, DMAP, CH2Cl2, 0 °C, 30 min, 90%.
was reduced to (Z)-olefin by using Pd/CaCO3 in AcOEt
Conclusions
to furnished the target molecule pectinolide H (4) in 98%
yield (Scheme 4).
In conclusion, we have successfully achieved a new stere-
25
The observed optical rotation of 4 was ½aꢂD = ꢀ42.8 oselective total synthesis of naturally occurring pectino-
25
(c = 0.2, CHCl3) {½aꢂD = ꢀ43.7 (c = 0.18, CHCl3) [6d]}. lides A, C, and H, by using commercially available
The optical rotation and spectroscopic data of the pre- (+)-diethyl L-tartrate as starting material. Mixed metal
pared compounds 1, 3, and 4 were in good agreement hydride reduction, Ohira–Bestmann reagent, selective
with those of the reported natural and synthetic products.
reduction in ketone with Corey–Bakshi–Shibata catalyst,
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Helv. Chim. Acta 2016, 99, 247 – 254
Scheme 4
a) TBAF, THF, 0 °C – r.t., 3 h, 90%; b) DDQ, CH2Cl2-H2O 20:1, r.t., 2 h, 85%; c) Lindlar’s catalyst, quinoline, AcOEt, r.t., 30 min, 98%.
CꢁC bond reduction with Lindlar’s catalyst, and and the residue was extracted with AcOEt (2 9 25 ml). The
Still–Gennari cis-olefination are the key reactions.
org. layer was washed with sat. NaHCO3 soln. and brine,
dried (Na2SO4), and concentrated to give 6 (5.5 g, 70%) as a
26
RSG and SBW are thankful to CSIR-New Delhi for yellow-colored liquid. ½aꢂD = ꢀ35.1 (c = 1, CHCl3). IR
providing fellowships and AVN is thankful to ORIGIN (neat): 2982, 2924, 2851, 1737, 1614, 1517, 1394, 1215, 1096,
project (CSC-108) for financial assistance.
1026, 830, 770. 1H-NMR (CDCl3, 300 MHz): 7.52 (d, J = 8.7,
2 H); 6.91 (d, J = 8.7, 2 H); 6.11 (s, 1 H); 4.92 (d, J = 4.1,
1 H); 4.81 (d, J = 4.1 H, 1); 4.35 – 4.26 (m, 4 H); 3.82 (s, 3
H); 1.38 – 1.30 (m, 6 H). 13C-NMR (CDCl3, 75 MHz):
169.6; 169.1; 160.8; 128.7; 127.5; 113.6; 106.6; 77.4; 77.1; 61.9;
55.2; 14.1; 14.0. ESI-MS: 347 [(M + Na)+], 325 [(M + H)+].
Experimental Part
General
All reagents were purchased from commercial sources
and were used without further purification. All reactions
(2S,3S)-3-[(4-Methoxybenzyl)oxy]butane-1,2,4-triol (7).
were performed under an inert atmosphere unless noted To a stirred soln. of AlCl3 (4.4 g, 33.1 mmol) in dry THF
otherwise. THF was freshly distilled over Na-benzophe- (25 ml), a soln. of LiAlH4 (1.25 g, 33.1 mmol) in dry
none ketyl. Petroleum ether refers to the fraction boiling
THF (20 ml) at ꢀ30 °C was added. Then, dry CH2Cl2
in the 60 – 80 °C range. TLC: precoated SiO2 60 F254 (20 ml) was added and the temperature was allowed to
plates (Merck, Darmstadt, Germany); visualization under rise to 0 °C. After 10 min, a soln. of 6 (5.4 g, 16.5 mmol)
UV light, in an I2 chamber, or by spraying with phospho-
molybdic acid. Column chromatography (CC): silica gel
in dry CH2Cl2 (15 ml) was added to the above mixture,
which was then stirred at room temperature for 1 h and
€
(SiO2; Acme grade 60 – 120 mesh). Mp.: Buchi M-560 heated at reflux for 2 h. Then, the mixture was cooled to
melting point apparatus, Vakola, Mumbai, India; uncor-
ꢀ20 °C and the reaction quenched by adding H2O
rected. Optical rotations: Rudolph Autopol IV polarime- (1.5 ml) followed by 10% aq. KOH soln. (2 ml). The
ter (Rudolph Research Analytical, Hackettstown, NJ, mixture was warmed to room temperature, stirred until
USA) at 278. IR Spectra: PerkinElmer FT-IR 240-c spec- the gray color disappeared, then filtered through a Celite
trophotometer (PerkinElmer, Waltham, MS, USA); ṽ in bed, and the precipitate was washed with CH2Cl2
cmꢀ1
.
1H- and 13C-NMR spectra: Bruker-300 MHz spec- (2 9 50 ml). The combined filtrates were concentrated,
trometer (Burker Corp. Fallanden, Switzerland); in and the residue was purified by CC (SiO2; AcOEt/iPrOH,
CDCl3, at 300 and 75 MHz, resp.; d in ppm rel. to Me4Si 9:1) to give triol 7 (2.82 g 70%) as a colorless liquid,
€
26
as internal standard, J in Hz. MS: Finnigan MAT 1020 ½aꢂD = 38 (c = 1.3, CHCl3). IR (neat): 3394, 2927, 1611,
1
mass spectrometer (Finnigan, Ringoes, NJ, USA), operat-
ing at 70 eV; in m/z.
1513, 1464, 1246, 1219, 1031, 821, 772. H-NMR (CDCl3,
300 MHz): 7.26 (d, J = 8.5, 2 H); 6.89 (d, J = 8.5, 2 H);
4.64 (d, J = 11.1, 1 H); 4.51 (d, J = 11.1, 1 H); 3.91 – 3.48
(m, 6 H); 3.85 (s, 3 H); 2.90 (br. s, 1 H); 1.76 (br. s, 2 H).
13C-NMR (CDCl3, 75 MHz): 159.3; 129.7; 129.6; 129.5;
Diethyl (4R,5R)-2-(4-Methoxyphenyl)-1,3-dioxolane-4,5-
dicarboxylate (6). To a stirred mixture of p-methoxybenzal-
dehyde dimethyl acetal (6.2 ml, 36.4 mmol) and (+) diethyl 113.8; 78.7; 72.1; 71.6; 63.2; 60.4; 55.1. ESI-MS: 265
L-tartrate (5 g, 24.2 mmol) in toluene (50 ml), PTSA
(0.92 g, 4.8 mmol) was added. The resulting mixture was
[(M + Na)+].
heated to reflux using a Dean–Stark trap to azeotropic (2S)-2-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2-[(4-meth-
removal of H2O for 8 h. Then, the solvent was concentrated oxybenzyl)oxy]ethanol (8). To a stirred soln. of 7 (2.6 g,
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Helv. Chim. Acta 2016, 99, 247 – 254
251
10.7 mmol) in dry acetone (40 ml) at ꢀ60 °C, 2,2-DMP stirred for 30 min, and added a soln. of pentanal (0.75 g,
(Me2C(OMe)2; (1.4 ml, 11.2 mmol) and PTSA (20 mg, 8.5 mmol) dissolved in dry THF (5 ml). The resulting
0.1 mmol) were added at the same temperature and the
mixture was stirred for 1 h. Then, the reaction was quen-
mixture was stirred for 3 h at ꢀ78 °C. The reaction mix-
ture was quenched with sat. aq. NH4Cl soln. (10 ml) and
ched by adding NaHCO3 (50 mg) and the mixture stirred extracted with AcOEt (2 9 25 ml), the combined organic
for 30 min, and filtered. The filtrate was concentrated to extract washed with brine, dried (Na2SO4), and concen-
give a crude product, which was purified by CC (neutral trated. The residue was purified by CC (SiO2; AcOEt/
Al2O3; AcOEt/hexane 2:8) to give compound 8 as pale hexane 1:9) to give diastereoisomeric mixture of propargylic
26
yellow liquid, yield; 2.67 g (85%). ½aꢂD = ꢀ26.2 (c = 0.8, alcohol 10 (1.67 g, 80%) as pale yellow oil. 1H-NMR
CHCl3). IR (neat): 3390, 2925, 1661, 1628, 1550, 1514,
(CDCl3, 300 MHz): 7.25 (d, J = 8.5, 2 H); 6.85 (d, J = 8.5, 2
1466, 1219, 772. 1H-NMR (CDCl3, 300 MHz): 7.29 (d, H); 4.73 (d, J = 11.7, 1 H); 4.57 – 4.34 (m, 2 H); 4.28 – 4.10
J = 8.7, 2 H); 6.89 (d, J = 8.7, 2 H); 4.70 (d, J = 11.4, 1 (m, 2 H); 3.96 – 3.88 (m, 2 H); 3.81 (s, 3 H); 1.83 – 1.61 (m,
H); 4.62 (d, J = 11.4, 1 H); 4.29 (dt, J = 6.7, 6.1 H, 1 H); 2 H); 1.55 – 1.20 (m, 10 H); 0.93 (t, J = 7.3, 3 H).
4.00 (dd, J = 8.3, 6.5 H, 1 H); 3.81 (s, 3 H); 3.80 – 3.77 13C-NMR (CDCl3, 75 MHz): 159.3; 129.7; 129.3; 128.6;
(m, 1 H); 3.75 – 3.64 (m, 1 H); 3.61 – 3.51 (m, 2 H); 1.43 113.7; 110.1; 80.8; 80.2; 77.2; 73.2; 69.8; 66.4; 62.3; 55.2; 37.3;
(s, 3 H); 1.37 (s, 3 H). 13C-NMR (CDCl3, 75 MHz): 27.2; 26.5; 25.2; 22.3; 13.9. ESI-MS: 385 [(M + Na)+].
159.3; 130.1; 129.5; 113.8; 109.4; 78.7; 76.5; 72.4; 65.5; 61.6;
55.2; 26.3; 25.2. ESI-MS: 305 [(M + Na)+].
(1S)-1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-1-[(4-meth-
oxybenzyl)oxy]oct-2-yn-4-one (11). To a stirred soln. of
dry CH2Cl2 (10 ml) and COCl2 (0.35 ml, 6.6 mmol) was
added dry DMSO (1.5 ml, 13.2 mmol) at ꢀ78 °C. Then a
soln. of 10 (1.6 g, 4.4 mmol) dissolved in CH2Cl2 (10 ml)
(4S)-4-{(1S)-1-[(4-Methoxybenzyl)oxy]prop-2-yn-1-yl}-
2,2-dimethyl-1,3-dioxolane (9). To a stirred soln. of dry
CH2Cl2 (20 ml) and COCl2 (1.2 ml, 13.8 mmol) was
added dry DMSO (2 ml, 27.6 mmol) at ꢀ78 °C. Then a was added and the mixture was stirred at the same tem-
soln. of alcohol 8 (2.6 g, 9.2 mmol) dissolved in CH2Cl2 perature for 2 h. Then Et3N (3 ml, 22 mmol) was added
(10 ml) was added and the mixture was stirred at the
same temperature for 2 h. Then Et3N (6.4 ml, 46 mmol) allowed to rise to 0 °C and quenched with sat. NH4Cl
was added and continued stirring for 30 min. Then, the soln. then, the mixture was extracted with CH2Cl2
mixture temperature was allowed to rise to 0 °C and (2 9 10 ml) and the combined organic extracts were
quenched with sat. NH4Cl soln. The mixture was extrac- washed with brine, dried (Na2SO4), and concentrated.
and continued stirring for 30 min. The mixture was
ted with CH2Cl2 (2 9 10 ml) and the combined organic The residue was purified by CC (SiO2; AcOEt/hexane
extracts were washed with brine, dried (Na2SO4), and 5:95) to give the pure ketone 11 (1.43 g, 90%) as color-
26
concentrated to give the aldehyde (2.33 g, 90%) which
was used for next reaction.
To a stirred soln. of K2CO3 (2.3 g, 16.6 mmol) and
less liquid. ½aꢂD = ꢀ13.6 (c = 1, CHCl3). IR (neat): 2957,
2931, 2871, 2211, 1677, 1585, 1513, 1461, 1375, 1248, 1219,
1075, 1034, 772. 1H-NMR (CDCl3, 300 MHz): 7.29 (d,
dimethyl-1-diazo-2-oxopropyl
phosphonate
(1.75 g, J = 8.2, 2 H); 6.89 (d, J = 8.2, 2 H); 4.77 (d, J = 11.7, 1
H); 4.30 – 4.22 (m, H);
9.1 mmol) in dry MeOH (20 ml) was added drop wise the H); 4.51 (d, J = 11.7,
1
1
above aldehyde (2.33 g, 8.3 mmol) which was dissolved in
dry MeOH (10 ml) at room temperature. The resulting
4.18 – 4.04 (m, 2 H); 4.01 – 3.88 (m, 1 H); 3.81 (s, 3 H);
2.58 (t, J = 7.4, 2 H); 1.73 – 1.58 (m, 3 H); 1.48 – 1.32 (m,
mixture was stirred for 2 h and confirmed the completion 7 H); 0.93 (t, J = 7.3, 3 H). 13C-NMR (CDCl3, 75 MHz):
of reaction by TLC. The reaction mixture was filtered 187.4; 159.5; 129.8; 128.6; 113.8; 110.2; 87.6; 85.6; 85.2;
through Celite pad and the filtrate was concentrated and
71.1; 69.2; 66.1; 55.2; 45.2; 26.4; 25.9; 25.1; 22.0; 13.7. ESI-
purified by CC (SiO2; AcOEt/hexane 1:9) to give the pure MS: 383 [(M + Na)+], 378 [(M + NH4)+].
26
alkyne 9 (1.65 g, 72%) as pale yellow oil. ½aꢂD = 27.8
(c = 1, CHCl3). IR (neat): 3278, 2987, 2922, 2853, 2113,
(1S,4S)-1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-1-[(4-
1612, 1513, 1217, 1068, 1034, 772. 1H-NMR (CDCl3, ethoxybenzyl)oxy]oct-2-yn-4-ol (12). To a stirred soln. of
300 MHz): 7.30 (d, J = 8.5, 2 H); 6.88 (d, J = 8.5, 2 H); 11 (1.4 g, 5.4 mmol) in dry THF (15 ml) was added
4.78 (d, J = 11.6, 1 H); 4.72 – 4.45 (m, 2 H); 4.35 – 4.20
(m, 1 H); 4.16 – 3.88 (m, 2 H); 3.81 (s, 3 H); 3.44 (d, toluene, 1.6 mmol) at ꢀ40 °C. After 30 min, stirring,
J = 9.4, 1 H); 1.40 (s, 3 H); 1.35 (s, 3 H). 13C-NMR
BH3.DMS (0.45 ml, 5.9 mmol) was added drop wise and
(CDCl3, 75 MHz): 159.3; 129.8; 129.4; 129.4; 113.8; 110.2; stirred at the same temperature for 1 h. After completion
(S)-(-)-methyl-CBS-oxazaborolidine (1.6 ml, 1 M soln. in
81.6; 80.8; 79.4; 75.5; 70.3; 66.2; 55.2; 26.4; 25.3. ESI-MS:
299 [(M + Na)+], 294 [(M + H)+].
of the reaction checked by TLC, the mixture was quen-
ched with MeOH (0.1 ml) followed by sat. NaHCO3 soln.
Then the reaction mixture was extracted with AcOEt
(2 9 15 ml) and the combined organic layers were
washed with brine, dried (Na2SO4), and concentrated.
The crude product was purified by CC (SiO2; AcOEt/hex-
ane 1:9) to give secondary alcohol 12 (1.26 g, 90%) as
1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-1-[(4-methoxyben-
zyl)oxy]oct-2-yn-4-ol (10). To a stirred soln. of 9 (1.6 g,
5.7 mmol) in dry THF (10 ml) was added BuLi (4.3 ml,
6.9 mmol; 1.6M in hexane) at ꢀ78 °C. The mixture was
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Helv. Chim. Acta 2016, 99, 247 – 254
pale yellow liquid with de >96%. Diastereomeric excess 129.8; 129.7; 128.9; 113.8; 85.9; 81.2; 73.4; 72.7; 70.9; 64.0;
measured by reverse phase HPLC column XDB-C18 (7:3 63.0; 55.2; 34.2; 27.1; 22.1; 20.9; 13.8. ESI-MS: 387
CH3CN/H2O, flow rate 1 ml/min, 200 nm), tR: 1.755 (ma-
26
[(M + Na)+], 382 [(M + NH4)+].
jor) and tR: 2.531 (minor). ½aꢂD = ꢀ3.8 (c = 1, CHCl3). IR
(neat): 3395, 2954, 2929, 2859, 1612, 1513, 1463, 1375,
1247, 1034, 772. 1H-NMR (CDCl3, 300 MHz): 7.29 (d, methoxybenzyl)oxy]dec-6-yn-5-yl Acetate (15). To a stir-
(5S,8S,9S)-9,10-bis{[tert-Butyl(dimethyl)silyl]oxy}-8-[(4-
J = 8.8, 2 H); 6.88 (d, J = 8.8, 2 H); 4.75 (d, J = 11.7, 1
red soln. of 14 (0.9 g, 2.5 mmol) in dry CH2Cl2 (10 ml) was
t
H); 4.58 – 4.34 (m, 2 H); 4.31 – 4.13 (m, 2 H); 4.12 – 4.01 added pyridine (0.68 g, 10 mmol) and BuMe2SiCl (0.83 g,
(m, 1 H); 3.98 – 3.88 (m, 1 H); 3.81 (s, 3 H); 1.83 – 1.62 5.5 mmol) at 0 °C. Then, the reaction mixture was stirred
(m, 2 H); 1.55 – 1.21 (m, 10 H); 0.93 (t, J = 7.3, 3 H). at room temperture for 1 h. Crushed ice was added and the
13C-NMR (CDCl3, 75 MHz): 159.3; 129.7; 129.2; 128.5; mixture was extracted with CH2Cl2 (2 9 15 ml). The org.
113.7; 110.1; 88.7; 80.8; 80.2; 73.2; 69.9; 66.3; 62.3; 55.2;
extracts were washed with brine, dried (Na2SO4), and con-
37.3; 27.2; 26.5; 25.2; 22.3; 13.9. ESI-MS: 385 [(M + Na)+], centrated. The crude product was purified by CC (SiO2;
380 [(M + NH4)+].
AcOEt/hexane 3:7) to give the compound 15 (1.31 g, 90%)
26
as colorless syrup. ½aꢂD = 14.6 (c = 1, CHCl3). IR (neat):
2953, 2928, 2856, 1744, 1612, 1513, 1465, 1367, 1247, 1228,
1
1083, 1037, 832, 773. H-NMR (CDCl3, 300 MHz): 7.28 (d,
(1S,4S)-1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-1-[(4-ethox-
ybenzyl)oxy]oct-2-yn-4-yl Acetate (13). To stirred soln. of
J = 8.4, 2 H); 6.85 (d, J = 8.4, 2 H); 5.50 – 5.30 (m, 1 H);
12 (1.2 g, 3.3 mmol) in dry CH2Cl2 (15 ml) was added 4.71 (d, J = 11.3, 1 H); 4.51 – 4.37 (m, 2 H); 4.27 – 4.12 (m,
pyridine (0.35 ml, 4.3 mmol) at 0 °C. After 10 min, stir-
ring, Ac2O (0.4 ml, 4 mmol) followed by cat. DMAP
were added. The reaction mixture was then allowed to
stir for 30 min, at room temperature. After completion
of the reaction as indicated by TLC, cold H2O was
poured into reaction mixture (10 ml) and extracted with
1 H); 3.81 (s, 3 H); 3.84 – 3.78 (m, 1 H); 3.71 – 3.55 (m, 1
H); 2.08 (s, 3 H); 1.84 – 1.62 (m, 2 H); 1.50 – 1.22 (m, 4 H);
0.98 – 0.78 (m, 21 H); 0.18 – 0.03 (m, 12 H). 13C-NMR
(CDCl3, 75 MHz): 169.8; 159.1; 129.9; 129.6; 129.1; 113.6;
84.3; 82.5; 75.4; 72.9; 70.4; 64.6; 64.1; 55.2; 34.5; 27.1; 25.9;
25.8; 22.2; 21.0; 18.1; 13.8; ꢀ4.4; ꢀ4.7; ꢀ4.8; ꢀ5.4. ESI-MS:
CH2Cl2 (2 9 10 ml). The combined organic layers were 610 [(M + NH4)+].
washed with brine, dried (Na2SO4), and concentrated. The
crude product was purified by CC (SiO2; AcOEt/hexane (5S,8S,9S)-9-{[tert-Butyl(dimethyl)silyl]oxy}-10-hydroxy-
5:95) to give the pure acetate 13 (1.23 g, 92%) as colorless 8-[(4-methoxybenzyl)oxy]dec-6-yn-5-yl Acetate (16). To
26
oil. ½aꢂD = ꢀ14.6 (c = 1, CHCl3). IR (neat): 2955, 2931,
a stirred soln. 15 (1.25 g, 2.1 mmol) in CH2Cl2/MeOH
2866, 1742, 1612, 1513, 1371, 1222, 1074, 1033, 772. 1H- (20 ml, 3:1) was added CSA (50 mg, 0.2 mmol) at 0 °C and
NMR (CDCl3, 300 MHz): 7.29 (d, J = 8.4, 2 H); 6.87 (d, continued stirring for 1 h. After completion of the reaction,
J = 8.4, 2 H); 5.49 – 5.35 (m, 1 H); 4.75 (d, J = 11.5, 1 H); the mixture was quenched by adding sat. aq. NaHCO3 and
4.56 – 4.44 (m, 2 H); 4.29 – 4.13 (m, 1 H); 4.12 – 4.01 (m, 1
extracted with CH2Cl2 (2 9 10 ml). The combined organic
H); 3.99 – 3.85 (m, 1 H); 3.81 (s, 3 H); 2.08 (s, 3 H); extracts were washed with brine, dried (Na2SO4), and con-
1.87 – 1.67 (m, 2 H); 1.54 – 1.21 (m, 10 H); 0.91 (t, J = 7.3,
centrated. The crude product was purified by CC (SiO2;
3 H). 13C-NMR (CDCl3, 75 MHz): 169.8; 159.3; 129.8; AcOEt/hexane 3:7) to give alcohol 16 (0.8 g, 80%), as yel-
26
129.7; 129.2; 113.7; 110.1; 84.0; 82.1; 81.3; 73.2; 69.8; 66.2;
63.8; 55.2; 34.2; 27.1; 26.4; 25.3; 22.1; 20.9; 13.8. ESI-MS: 427 2954, 2928, 2856, 1742, 1612, 1513, 1465, 1370, 1247, 1222,
[(M + Na)+], 422 [(M + NH4)+].
lowish liquid; ½aꢂD = ꢀ3.7 (c = 1, CHCl3). IR (neat): 3395,
1225, 1036, 772. 1H-NMR (CDCl3, 300 MHz): 7.27 (d,
J = 8.5, 2 H); 6.87 (d, J = 8.5, 2 H); 5.52 – 5.36 (m, 1 H);
4.72 (d, J = 11.2, 1 H); 4.42 (d, J = 11.2, 1 H); 4.18 – 4.12
(5S,8S,9S)-9,10-Dihydroxy-8-[(4-methoxybenzyl)oxy]dec-
6-yn-5-yl Acetate (14). To a stirred soln. of 13 (1.2 g, 3 mmol) (m, 1 H); 3.86 – 3.60 (m, 3 H); 3.81 (s, 3 H); 2.08 (s, 3 H);
in CH2Cl2 was added 50% aq. soln. of TFA at 0 °C. After 1.83 – 1.72 (m, 2 H); 1.50 – 1.26 (m, 4 H); 0.96 – 0.84 (m,
30 min, reaction was quenched by sat. NaHCO3 soln. and 12 H); 0.03 (m, 6 H). 13C-NMR (CDCl3, 75 MHz): 169.9;
extracted with CH2Cl2 (2 9 10 ml). The combined organic 159.2; 129.7; 129.3; 129.2; 113.6; 84.6; 82.5; 73.8; 70.8; 70.3;
layer was washed with brine, dried (Na2SO4), and concen-
trated. The crude product was purified by CC (SiO2; ꢀ4.9. ESI-MS: 501 [(M + Na)+], 496 [(M + NH4)+].
64.1; 64.0; 55.2; 34.3; 27.1; 25.7; 22.1; 20.9; 18.0; 13.8; ꢀ4.6;
AcOEt/hexane 3:7) to give diol 14 (0.97 g, 90%) as yellow-
26
ish liquid. ½aꢂD = ꢀ27.1 (c = 1, CHCl3). IR (neat): 3457,
Methyl (2Z,4S,5S,8S)-8-(Acetyloxy)-4-{[tert-butyl(dime-
thyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]dodec-2-en-6-yno-
2954, 2923, 2854, 1738, 1612, 1513, 1371, 1228, 1028, 772.
1H-NMR (CDCl3, 300 MHz): 7.28 (d, J = 8.5, 2 H); 6.88 (d, ate (17). To a stirred soln. of dry CH2Cl2 (5 ml) and alcohol
J = 8.5, 2 H); 5.47 – 5.30 (m, 1 H); 4.76 (d, J = 11.1, 1 H); 16 (0.75 g, 1.56 mmol) was added NaHCO3 (0.13 g,
4.44 (d, J = 11.1, 1 H); 4.29 – 4.14 (m, 1 H); 3.93 – 3.63 (m, 1.56 mmol) at 0 °C. After 5 min, Dess–Martin periodinane
3 H); 3.80 (s, 3 H); 2.91 (br. s, 1 H); 2.84 (br. s, 1 H); 2.09 (s, (0.8 g, 1.9 mmol) was added and continued stirring for 1 h
3 H); 1.88 – 1.68 (m, 2 H); 1.50 – 1.20 (m, 4 H); 0.92 (t, at the same temperature. Then reaction mixture was quen-
J = 7.5, 3 H). 13C-NMR (CDCl3, 75 MHz): 170.0; 159.4; ched by adding Na2SO3 (0.4 g, 3.1 mmol) and continue
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Helv. Chim. Acta 2016, 99, 247 – 254
253
stirred for 30 min. The mixture was extracted with CH2Cl2 ring at room temperature for 3 h. Then, the solvent was
(2 9 10 ml) and the combined organic extracts were removed under reduced pressure and residue was adsor-
washed with brine, dried (Na2SO4), and concentrated. The
crude product was purified by CC (SiO2; AcOEt/hexane hexane 4:6) to give pure alcohol 19 (95 mg, 90%) as col-
bed on silica gel and purified by CC (SiO2; AcOEt/
26
2:8) to give aldehyde (0.67 g, 90%) which was used for next
reaction.
To a stirred soln. of dry THF (10 ml) and methyl-2-
orless liquid; ½aꢂD = 42.8 (c = 1, CHCl3). IR (neat): 3447,
2927, 2855, 1724, 1639, 1373, 1224, 1106, 712. 1H-NMR
(CDCl3, 300 MHz): 6.80 (dd, J = 9.8, 3.5, 1 H); 6.10 (d,
[bis(2,2,2-trifluoroethoxy) phosphoryl] acetate (0.53 g, J = 9.8, 1 H); 5.36 (dd, J = 5.4, 2.5 H, 1 H); 4.38 – 4.28
1.7 mmol) was added NaH (37 mg, 1.54 mmol) at 0 °C (m, 2 H); 2.10 (s, 3 H); 1.86 – 1.68 (m, 2 H); 1.48 – 1.26
and continued stirring for 30 min. Then the reaction mix-
ture was cooled to ꢀ78 °C and added the above aldehyde 75 MHz): 170.2; 161.1; 142.6; 124.8; 86.1; 83.8; 73.7; 71.1;
(m, 4 H); 0.96 (t, J = 7.5, 3 H). 13C-NMR (CDCl3,
(0.67 g, 1.4 mmol) dissolved in dry THF (5 ml) and con-
64.3; 34.5; 27.4; 22.4; 21.2; 14.1. ESI-MS: 289 [(M + Na)+],
tinue stirred for 1 h at ꢀ78 °C. The reaction was then 284 [(M + NH4)+].
quenched with sat. NH4Cl, solvent was removed under
reduced pressure and the residue was extracted with
AcOEt (2 9 10 ml). The combined organic extracts were
washed with brine, dried (Na2SO4), and concentrated.
(1Z,3S)-1-[(2S,3S)-3,6-Dihydro-3-hydroxy-6-oxo-2H-pyran-
2-yl]hept-1-en-3-yl Acetate (3). The stirred mixture of 19
(70 mg, 0.26 mmol) and Pd/CaCO3 (Lindlar catalyst)
The crude product was purified by CC (SiO2; AcOEt/hex- (50 mg) was poisoned by adding one drop of quinoline in
ane 1:9) to give pure (Z)-olefin ester 17 (0.65 g, 85%) as AcOEt (3 ml) for 30 min, at room temperature under H2
colorless liquid; ½aꢂD = ꢀ15.5 (c = 1, CHCl3). IR (neat): atmosphere. After completion of reaction, the mixture
2927, 2855, 1745, 1726, 1662, 1462, 1373, 1232, 1190, 1053, was filtered through Celite pad and filtrate was concen-
879. H-NMR (CDCl3, 300 MHz): 7.29 (d, J = 8.7, 2 H); trated and purified by CC (SiO2; AcOEt/hexane 4:6) to
6.88 (d, J = 8.5, 2 H); 6.38 (dd, J = 9.6, 3.7 H, 1 H); 5.96 give (Z)-olefin (69 mg, 98%) as colorless oil.
26
1
3
25
25
(d, J = 11.9, 1 H); 5.50 – 5.38 (m, 1 H); 4.74 (d, J = 11.4, ½aꢂD = 77.8 (c = 0.5, MeOH), lit. ½aꢂD = 80.9 (c = 0.76,
25
1 H); 4.48 – 4.38 (m, 2 H); 4.18 (d, J = 6.2, 1 H); 3.81 (s, MeOH) [3], ½aꢂD = 72.4 (c = 0.5, MeOH) [6b]. IR (neat):
3 H); 3.63 (s, 3 H); 2.08 (s, 3 H); 1.80 – 1.70 (m, 2 H); 3447, 2957, 2927, 2858, 1730, 1661, 1373, 1248, 1167, 1042,
1.48 – 1.28 (m, 4 H); 0.98 – 0.86 (m, 12 H); 0.05 (m, 6 H). 830, 775. 1H-NMR (CDCl3, 300 MHz): 6.88 (dd, J = 9.8,
13C-NMR (CDCl3, 75 MHz): 169.9; 166.1; 159.2; 146.1; 5.6, 1 H); 6.18 (d, J = 9.8, 1 H); 5.80 – 5.68 (m, 2 H); 5.52
129.8; 129.2; 120.1; 113.8; 84.6; 82.5; 73.8; 70.8; 70.4; 64.0;
(ddd, J = 9.8, 7.6, 5.8 H, 1H); 5.28 (dd, J = 6.1, 5.2 H, 1
55.2; 51.5; 34.5; 27.1; 25.7; 22.1; 21.0; 18.0; 13.8; ꢀ4.6; H); 4.13 (dd, J = 5.6, 2.4 H, 1 H); 2.08 (s, 3 H);
ꢀ4.9. ESI-MS m/z: 550 [(M + NH4)+].
1.78 – 1.54 (m, 2 H); 1.46 – 1.22 (m, 4 H); 0.94 (t, J = 7.5,
3 H). 13C-NMR (CDCl3, 75 MHz): 170.3; 162.0; 144.6;
133.3; 125.7; 122.5; 77.4; 70.8; 63.1; 34.7; 27.5; 22.6; 21.4;
14.3. ESI-MS m/z: 286 [(M + NH4)+].
(3S)-1-[(2S,3S)-3-{[tert-Butyl(dimethyl)silyl]oxy}-3,6-
dihydro-6-oxo-2H-pyran-2-yl]hept-1-yn-3-yl Acetate (18).
To a stirred soln. of 17 (300 mg, 0.56 mmol) in CH2Cl2/
H2O (5 ml, 20:1) mixture was added DDQ (254 mg, (2S,3S)-2-[(1Z,3S)-3-(Acetyloxy)hept-1-en-1-yl]-3,6-dihy-
1.1 mmol) at room temperature and continued stirring for
2 h. After completion of reaction, then, the mixture was
quenched by adding sat. aq. NaHCO3 and extracted with
dro-6-oxo-2H-pyran-3-yl Acetate (1). To stirred soln. of 3
(40 mg, 0.15 mmol) in dry CH2Cl2 (2 ml), pyridine
(15 ll, 0.18 mmol) was added at 0 °C. After 10 min, was
CH2Cl2 (2 9 5 ml). The combined organic extracts were added Ac2O (17 ll, 0.16 mmol) followed by cat. DMAP.
washed with brine, dried over Na2SO4, and concentrated. The reaction mixture was then allowed to stir for 30 min,
The crude product was purified by CC (SiO2; AcOEt/hex- at room temperature. After completion of the reaction as
ane 2:8) to give cyclized lactone 18 (180 mg 85%) as yel-
26
indicated by TLC, cold H2O was poured into reaction
low liquid; ½aꢂD = 18.3 (c = 1, CHCl3). IR (neat): 2924,
mixture (2 ml) and extracted with CH2Cl2 (2 9 2 ml).
2854, 1722, 1638, 1457, 1372, 1271, 1220, 1105, 771. 1H- The combined organic layers were washed with brine,
NMR (CDCl3, 300 MHz): 6.84 (dd, J = 9.6, 3.5 H, 1 H); dried (Na2SO4), and concentrated. The crude product
6.12 (d, J = 9.8, 1 H); 5.38 (dd, J = 5.3, 2.4 H, 1 H); was purified by CC (SiO2; AcOEt/hexane 25:75) mixture
4.42 – 4.34 (m, 2 H); 2.10 (s, 3 H); 1.68 – 1.54 (m, 2 H); to give the pure acetate 1 (41 mg, 90%) as colorless oil.
1.44 – 1.30 (m, 4 H); 0.94 – 0.80 (m, 12 H); 0.08 (m, 6 H). ½aꢂD = 190.2 (c = 0.5, MeOH), lit. ½aꢂD = 191.3 (c = 0.5,
13C-NMR (CDCl3, 75 MHz): 170.3; 161.4; 140.1; 125.7; MeOH) [6b]. IR (neat): 2956, 2931, 2859, 1747, 1463,
85.0; 83.0; 75.8; 74.5; 64.4; 34.7; 27.5; 26.1; 22.6; 21.4; 18.4; 1372, 1232, 1078, 1023, 838, 779. 1H-NMR (CDCl3,
14.3; ꢀ4.2; ꢀ4.5. ESI-MS: 398 [(M + NH4)+].
25
25
300 MHz): 6.92 (dd, J = 9.8, 5.6 H, 1 H); 6.22 (d, J = 9.8,
1 H); 5.75 (dd, J = 11.6, 8.5 H, 1 H); 5.62 (d, J = 9.8, 1
H); 5.50 (dd, J = 8.5, 3.0 H, 1 H); 5.33 (ddd, J = 9.8, 7.5,
6.0 H, 1 H); 5.16 (dd, J = 6.1, 3.2 H, 1 H); 2.08 (s, 3 H);
(3S)-1-[(2S,3S)-3,6-Dihydro-3-hydroxy-6-oxo-2H-pyran-
2-yl]hept-1-yn-3-yl Acetate (19). To a stirred soln. of 18
(150 mg, 0.4 mmol) in dry THF (5 ml) at 0 °C was added 2.04 (s, 3 H); 1.82 – 1.72 (m, 2 H); 1.46 – 1.24 (m, 4 H);
TBAF (0.8 ml, 1M, THF, 0.8 mmol) and continued stir-
0.90 (t, J = 7.5, 3 H). 13C-NMR (CDCl3, 75 MHz): 170.2;
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254
Helv. Chim. Acta 2016, 99, 247 – 254
169.8; 162.1; 140.1; 133.6; 126.2; 125.0; 75.0; 69.2; 64.3;
34.2; 27.1; 22.1; 21.0; 20.8; 13.8. ESI-MS: 311 [(M + H)+].
NMR (CDCl3, 300 MHz): 7.55 (dd, J = 6.0, 1.5 H, 1 H);
6.21 (dd, J = 5.3, 2.2 H, 1 H); 5.54 – 5.35 (m, 3 H); 5.15
(dt, J = 5.3, 1.5 H, 1 H); 4.96 (dd, J = 7.5, 5.3 H, 1 H);
3.74 (d, J = 3.0, 1 H); 2.08 (s, 3 H); 1.73 – 1.50 (m, 2 H);
1.36 – 1.24 (m, 4 H); 0.88 (t, J = 7.5, 3 H). 13C-NMR
(CDCl3, 75 Mz): 172.5; 170.5; 153.1; 133.4; 128.7; 123.5;
(1S,4S)-1-[(4-methoxybenzyl)oxy]-1-(5-oxo-2,5-dihydro-
furan-2-yl)oct-2-yn-4-yl Acetate (20). To a stirred soln. of
17 (250 mg, 0.8 mmol) in dry THF (5 ml) at 0 °C was
added TBAF (1.6 ml, 1 M, THF, 0.16 mmol) and continued 84.6; 70.1; 65.5; 34.1; 27.2; 22.3; 21.1; 13.9. ESI-MS m/z:
stirring at room temperature for 3 h. Then the reaction mix- 291 [(M + Na)+], 286 [(M + NH4)+].
ture was concentrated and the obtained residue was purified
by CC (SiO2; AcOEt/hexane 2:8) to give lactone 20
26
REFERENCES
(163 mg, 90%) as colorless liquid. ½aꢂD = ꢀ27.3 (c = 0.5,
[1] T. Hamamoto, H. Seto, T. Beppu, J. Antibiot. 1983, 36, 646;
M. S. Butler, J. Nat. Prod. 2004, 67, 2141; D. J. Newman, G.
M. Cragg, J. Nat. Prod. 2007, 70, 461.
CHCl3). IR (neat): 2957, 2934, 2873, 1744, 1660, 1459, 1373,
1233, 1162, 1050, 849. 1H-NMR (CDCl3, 300 MHz):
7.54 – 7.48 (m, 1 H); 7.35 (d, J = 8.6, 2 H); 6.87 (d, J = 8.6,
2 H); 6.19 (d, J = 11.9, 1 H); 5.36 – 5.28 (m, 2 H); 5.12 (dd,
J = 6.2, 3.7 H, 1 H); 4.88 (d, J = 11.4, 1 H); 4.57 (d,
J = 11.4, 1 H); 3.81 (s, 3 H); 2.08 (s, 3 H); 1.78 – 1.68 (m, 2
H); 1.48 – 1.18 (m, 4 H); 0.90 (t, J = 7.6, 3 H). 13C-NMR
(CDCl3, 75 MHz): d 172.2; 170.2; 152.7; 129.8; 129.2; 123.1;
113.8; 85.2; 84.5; 84.2; 65.1; 63.7; 55.2; 33.8; 26.8; 21.9; 20.7;
13.6. ESI-MS: 409 [(M + Na)+], 387 [(M + H)+].
ꢀ
[2] R. Pereda-Miranda, L. Hernandez, M. J. Villavicencio, M. Novelo,
P. Ibarra, H. Chai, J. M. Pezzuto, J. Nat. Prod. 1993, 56, 583.
[3] M. Fragoso-Serrano, S. Gibbons, R. Pereda-Miranda, Planta
Med. 2005, 71, 278.
[4] M. Martinez, ‘Las Plantas Medicinales de Mexico’, Ed. Botas,
Mexico, 1989, p. 508.
[5] K. Malan, Y. Pelissier, C. Marion, A. Blaise, J.-M. Blessiere,
Planta Med. 1988, 54, 531.
[6] a) J. S. Yadav, S. S. Mandal, Tetrahedron Lett. 2011, 52, 5747;
b) G. Sabitha, S. K. Das, P. A. Reddy, J. S. Yadav, Tetrahedron
Lett. 2013, 54, 1097; c) T. V. Kumar, G. Shankaraiah, K. S.
Babu, J. M. Rao, Tetrahedron Lett. 2013, 54, 1397; d) D.
Ramesh, V. Shekhar, D. Chantibabu, S. Rajaram, U. Ramulu,
Y. Venkateswarlu, Tetrahedron Lett. 2012, 53, 1258; e) G.
Sabitha, P. A. Reddy, S. K. Das, J. S. Yadav, Synthesis 2013, 45,
651; f) U. Ramulu, D. Ramesh, S. P. Reddy, S. Rajaram, K. S.
Babu, Tetrahedron: Asymmetry 2014, 25, 1409; g) G. Sabitha, P.
A. Reddy, S. K. Das, Synthesis 2015, 47, 330; h) R. Perla, N. W.
Fadnavis, Eur. J. Chem. 2015, 6, 93.
(1S,4S)-1-(2,5-Dihydro-5-oxofuran-2-yl)-1-hydroxyoct-2-
yn-4-yl Acetate (21). To a stirred soln. of 20 (140 mg, 0.36
mmol) in CH2Cl2/H2O (5 ml, 20:1) was added DDQ
(160 mg, 0.72 mmol) at room temperature, and continued
stirring for 2 h. After completion of reaction, mixture was
quenched by adding sat. aq. NaHCO3 soln. and extracted
with CH2Cl2 (2 9 5 ml). The combined organic extracts
were washed with brine, dried (Na2SO4), and concentrated.
The crude product was purified by CC (SiO2; AcOEt/
hexane 3:7) to give alcohol 21 (82 mg, 85%) as yellowish
[7] R. S. Ghogare, S. B. Wadavrao, A. V. Narsaiah, Tetrahedron
Lett. 2013, 54, 5674; B. Nagaiah, A. V. Narsaiah, Helv. Chim.
Acta 2013, 96, 1948; S. B. Wadavrao, A. Narikimalli, A. V. Nar-
saiah, Synthesis 2013, 45, 3383; J. K. Kumar, A. V. Narsaiah,
Org. Commun. 2014, 7, 28; B. Nagaiah, A. V. Narsaiah, Synth.
Commun. 2014, 44, 1227; S. B. Wadavrao, R. S. Ghogare, A. V.
Narsaiah, Helv. Chim. Acta 2015, 98, 575; S. B. Wadavrao, R. S.
Ghogare, A. V. Narsaiah, Synthesis 2015, 47, 2129.
26
liquid. ½aꢂD = ꢀ33.9 (c 0.3, CHCl3). IR (neat): 3409, 2958,
2933, 2869, 1740, 1660, 1373, 1239, 1161, 1054, 830.
1H-NMR (CDCl3, 300 MHz): 7.55 – 7.48 (m, 1 H); 6.20 (d,
J = 12.1, 1 H); 5.34 – 5.26 (m, 2 H); 5.12 (dt, J = 7.5, 2.1 H,
1 H); 2.08 (s, 3 H), 1.80 – 1.70 (m, 2 H); 1.43 – 1.29 (m, 4
H); 0.90 (t, J = 7.5, 3 H). 13C-NMR (CDCl3, 75 MHz):
172.3; 170.3; 152.8; 123.2; 85.3; 84.7; 84.4; 65.3; 63.8; 33.9;
26.9; 22.0; 20.9; 13.7. ESI-MS: 289 [(M + Na)+], 284
[(M + NH4)+].
[8] E. L. Eliel, Rec. Chem. Progr. 1961, 22, 129; S. S. Bhattacharjee,
P. A. J. Gorin, Carbohydrate Res. 1970, 12, 57; B. E. Leggetter,
R. K. Brown, Can. J. Chem. 1965, 43, 1030; X. Lu, H.-S. Byun,
R. Bittman, J. Org. Chem. 2004, 69, 5433.
[9] H.-L. Huang, R.-S. Liu J. Org. Chem. 2003, 68, 805.
[10] A. J. Mancuso, D. Swern, Synthesis 1981, 3, 165; K. Omura, D.
Swern, Tetrahedron 1978, 34, 1651.
€
(1S,2Z,4S)-1-[(2S)-2,5-Dihydro-5-oxofuran-2-yl]-1-hydro-
xyoct-2-en-4-yl Acetate (4). The stirred mixture of 21
(50 mg, 0.18 mmol) and Pd/CaCO3 (Lindlar’s catalyst)
(50 mg) was poisoned by adding one drop of quinoline in
AcOEt (2 ml) for 30 min, at room temperature under H2
atmosphere. After completion of reaction, mixture was
filtered through Celite pad and the filtrate was concen-
trated and purified by CC (SiO2; AcOEt/hexane mixture
3:7) to give (Z)-olefin 4 (49 mg, 98%) as colorless oil.
[11] S. Ohira, Synth. Commun. 1989, 19, 561; S. Muller, B. Liepold,
G. J. Roth, H. J. Bestmann, Synlett 1996, 521; J. Pietruszka, A.
Witt, Synthesis 2006, 4266; D. F. Taber, S. Bai, P.-F. Guo,
Tetrahedron Lett. 2008, 49, 6904.
[12] E. J. Corey, R. K. Bakshi, S. Shibata, J. Am. Chem. Soc. 1987,
109, 5551.
[13] D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155.
[14] W. C. Still, C. Gennari, Tetrahedron Lett. 1983, 24, 4405.
[15] H. Lindlar, R. Dubuis, Org. Synth. 1966, 46, 89.
Received May 5, 2015
Accepted January 25, 2016
25
½aꢂD = ꢀ42.8 (c = 0.2, CHCl3). IR (neat): 3446, 2956,
2857, 1750, 1461, 1372, 1248, 1167, 1041, 829, 774. 1H-
€
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