Radical photocyclization route for macrocyclic lactone ring expansion and conversion to macrocyclic lactams and ketones

Article abstract of DOI:10.1021/jo3024126

A new method for the synthesis of macrocyclic lactones, lactams, and ketones, which utilizes photoinduced intramolecular radical cyclization reactions of substrates containing tethered carboxylic acids and α,β-unsaturated carbonyl moieties, has been uncovered. Photocyclization of the carboxylic acids tethered acrylate ester, which were prepared starting from the macrocyclic lactones, gave the two-carbon elongated macrocyclic lactones via decarboxylation. Similar photoreactions of carboxylic acid tethered acryl amide or α,β-unsaturated ketone moieties, which were also prepared starting from the macrocyclic lactones, produced macrocyclic lactams or ketones, respectively. The simple approach can be readily applied to the preparation of a variety of macrocyclic lactones, lactams, and ketones with tunable ring sizes.

Full text of DOI:10.1021/jo3024126

Article
pubs.acs.org/joc
Radical Photocyclization Route for Macrocyclic Lactone Ring
Expansion and Conversion to Macrocyclic Lactams and Ketones
Keisuke Nishikawa,† Yasuharu Yoshimi,*,† Kousuke Maeda,† Toshio Morita,† Ichiro Takahashi,†
Tatsuya Itou,‡ Sho Inagaki,§ and Minoru Hatanaka§
†Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, University of Fukui, 3-9-1 Bunkyo, Fukui
910-8507, Japan
‡Graduate School of Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan
§Department of Medicinal and Organic Chemistry, School of Pharmacy, Iwate Medical University, Yahaba, Iwate 028-3694, Japan
S
* Supporting Information
ABSTRACT: A new method for the synthesis of macrocyclic lactones, lactams, and ketones, which utilizes photoinduced
intramolecular radical cyclization reactions of substrates containing tethered carboxylic acids and α,β-unsaturated carbonyl
moieties, has been uncovered. Photocyclization of the carboxylic acids tethered acrylate ester, which were prepared starting from
the macrocyclic lactones, gave the two-carbon elongated macrocyclic lactones via decarboxylation. Similar photoreactions of
carboxylic acid tethered acryl amide or α,β-unsaturated ketone moieties, which were also prepared starting from the macrocyclic
lactones, produced macrocyclic lactams or ketones, respectively. The simple approach can be readily applied to the preparation of
a variety of macrocyclic lactones, lactams, and ketones with tunable ring sizes.
phthalimides containing N-tethered carboxyl or trialkylsilyl
groups.5 While the reactions of the phthalimide derivatives take
place efficiently under mild conditions, they are limited by the
fact that products contain the 3-hydroxyphthalimidine moiety.
Recently, we reported that PET induced reactions of alphatic
carboxylic acids, taking place through decarboxylation of radical
cation intermediates, generate free alkyl radicals. The alkyl
radicals, formed in this manner, were found to react with a
variety of substrates to yield adducts in high yields.6 Particularly
instructive examples of this methodology are found in
photodecarboxylative reactions of carboxylic acids in which
carbon centered free radical intermediates undergo efficient
intermolecular radical addition to electron-deficient alkenes
even when only 1 equiv of the alkenes are used (Scheme 1).6c
These earlier observations led us to propose that PET-
promoted reactions of substrate containing linked carboxylic
acids and α,β-unsaturated carbonyl groups could be employed
as part of concise sequences to prepare macrocyclic lactones,
INTRODUCTION
■
Because they are found in a variety of natural products and
synthetic pharmaceuticals, many of which have strong
antibacterial and antitumor activities, macrocyclic lactones,
lactams, and ketones are fundamental substances that have
served as targets of organic and medicinal chemistry
investigations.1 The efforts have uncovered a number of
efficient methods for the synthesis of members of these
macrocyclic compound families, including those that rely on
transition-metal-catalyzed ring-closing methathesis,2 Yamaguchi
macrolactonization,3 and AIBN/Bu3SnH promoted intramo-
lecular radical cyclization.4 However, although being powerful,
these synthetic methodologies suffer from one or more
disadvantages associated with the use and/or production of
potentially environmentally unfriendly substances and less than
mild reaction conditions in macrocyclization.
Photoinduced electron transfer (PET) reactions can serve as
alternative methods to prepare macrocyclic compounds.
Importantly, these processes utilize light as an environmentally
clean and powerful reagent. Examples of this approach are
found in PET-promoted macrocyclization reactions of
Received: November 5, 2012
© XXXX American Chemical Society
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Scheme 1. Decarboxylative Intermolecular Radical Addition of Carboxylic Acid to Alkene
lactams, and ketones. As described below, studies aimed at
assessing the validity of this proposal have demonstrated that
the new photocyclization reactions, occurring under mild
conditions, can be employed as key components of a general
strategy for ring expansion of macrocyclic lactones and for
conversions of macrocyclic lactones to macrocyclic lactams and
ketones, although this method includes difficulties such as the
requirement of some steps for the preparation of substrates
containing tethered carboxylic acids and α,β-unsaturated
carbonyl moieties.
Table 1. PET-Promoted Cyclization of Carboxylic Acid 3 via
Decarboxylation
a
b
entry
1
3 (mM)
arene
Phen
electron acceptor
DCB
yield of 4 (%)
1
1
1
2
3
4
5
1
1
1
1
1
1
84
41
69
73
61
51
29
77
78
75
77
69
46
RESULTS AND DISCUSSION
■
c
2
Synthesis of Macrocyclic Lactones by Route Involving
PET-Promoted Cyclization of Carboxylic Acid Tethered
Acrylate Ester. Initial studies directed at exploring the new
PET-promoted cyclization strategy focused on the carboxylic
acid tethered acrylate ester 3. As previously reported by us,6c
the ester 3 was prepared in 84% yield starting from the 16-
membered macrocyclic lactone 1 through the formation of the
alcohol 2 using the simple four-step route (I + II) displayed in
Scheme 2.
d
3
4
5
6
7
8
Biphenyl
Phen
9
DCN
DCB
10
Biphenyl
Phen
e
11
f
12
g
Scheme 2. Preparation of Carboxylic Acid Tethered Acrylate
Ester 3
13
a
The photoreaction of 3 was carried out in the presence of 1 equiv of
NaOH, arene (20 mM), and electron acceptor (20 mM) using 100-W
high-pressure mercury lamp under an argon atmosphere for 6 h.
b
c
d
Isolated yield. In the absence of NaOH. Irradiation time was 12 h
e
in the absence of NaOH. Concentrations of Phen and DCB were 1
mM. Concentrations of Phen and DCB were 0.5 mM, and irradiation
time was 10 h. Concentrations of Phen and DCB were 0.2 mM, and
f
g
irradiation time was 18 h.
addition, the utilization of higher concentrations of 3 (2, 3, 4, 5
mM) and 1 equiv of NaOH led to the generation of 4 in lower
yields (73, 61, 51, 29%) along with polymeric materials (entries
4−7). These findings suggest that higher concentrations of 3
enhance competitive intermolecular radical addition reactions.
The PET-promoted reactions of 3, using either other arenes,
such as biphenyl, and electron acceptors, such as 1,4-
dicyanonaphthalene (DCN), or lower concentrations of Phen
and DCB (1 mM), also generated 4 in similar yields (entries
8−11). Although use of catalytic amounts of Phen and DCB
(0.5, 0.2 mM) in this photoreaction led to the formation of 4, a
prolonged irradiation time (10, 18 h) was required, and the
yield of 4 decreased (entries 12−13).
Irradiation (100 W high-pressure mercury lamp, Pyrex filter
(λ > 280 nm), argon atmosphere, 6 h, room temperature) of an
aqueous acetonitrile solution (CH3CN/H2O = 9:1) containing
phenanthrene (Phen, 20 mM), 1,4-dicyanobenzene (DCB, 20
mM), substrate 3 (1 mM), and NaOH (1 mM) led to the
formation of the18-membered macrocyclic lactone 4 in 84%
yield (III, entry 1, Table 1). When NaOH was absent from the
photoreaction mixture, a prolonged irradiation time was
required, suggesting that the carboxylate ion undergoes the
PET-promoted decarboxylation process more efficiently than
does the corresponding carboxylic acid (entries 2−3). In
In order to demonstrate the utility of this two-carbon ring
expansion protocol for the preparation of macrocyclic lactones,
repetitive carboxylic acid tethered acrylate ester forming and
PET-promoted cyclization reactions (I + II + III) were
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performed to transform the 18-membered macrocyclic lactone
4 to ring expanded 20-membered lactone 6 in a high yield
(Scheme 3). Similarly, the respective 19- and 21-membered
conditions (NaN3; Ph3P) (V). Amidation of 13 with acryloyl
chloride followed by saponification of the methyl ester with
NaOH gave the desired carboxylic acid tethered acryl amide
substrate 14 (VI) in an overall (7 steps, IV + V + VI) 68%
yield.
The PET-promoted cyclization reaction was carried out by
irradiation (see conditions above) of an aqueous acetonitrile
solution (CH3CN/H2O = 9:1) of 14 (1 mM) containing
NaOH (1 mM), Phen (20 mM), and DCB (20 mM). This
process smoothly generated the corresponding 18-membered
macrocyclic lactam 15 in 78% yield (entry 1, Table 2). In a
Scheme 3. Ring Expansion of Macrocyclic Lactones by the
Photoreaction
Table 2. PET-Promoted Cyclization of Carboxylic Acid 14
a
via Decarboxylation
b
entry
14 (mM)
arene
Phen
electron acceptor
DCB
yield of 15 (%)
1
2
3
4
5
6
7
1
2
3
4
1
1
1
1
78
49
38
21
75
76
71
69
Biphenyl
Phen
DCB
DCB
Biphenyl
Phen
macrocyclic lactones 9 and 11 were prepared starting with the
17-membered macrocyclic lactone 7 through a repetitive ring-
opening radical-cyclization sequence. The observation made in
the studies described above show that macrocyclic lactones
having desired ring sizes can be efficiently prepared by
employing the novel photochemical radical cyclization protocol.
Synthesis of Macrocyclic Lactams by Routes Involving
PET-Promoted Cyclization of Carboxylic Acid Tethered
Acryl Amides. The next phase of this investigation focused on
applications of the general strategy to the synthesis of
macrocyclic lactams. The key substrate 14, containing tethered
carboxylic acid and acryl amide moieties, used to probe this
application was prepared from macrocyclic lactone 1 by a route
featuring a Staudinger and amidation reaction sequence shown
in Scheme 4. Accordingly, ring opening of 1 by treatment with
KOH followed by methyl ester formation gave alcohol 12 (IV).
Conversion of the hydroxyl group in 12 to the corresponding
amine in 13 was performed by initial conversion to the
mesylate followed by implementation of the Staudinger
c
8
a
The photoreaction was carried out in the presence of 1 equiv of
NaOH, arenes (20 mM), and electron acceptor (20 mM) using 100-W
high-pressure mercury lamp under an argon atmosphere for 6 h.
b
c
Isolated yield. Concentrations of Phen and DCB were 1 mM.
manner that is similar to the cyclization reactions of the
corresponding carboxylic acid tethered acrylate ester substrate
3, lower yields of 15 were obtained when higher concentrations
of 14 (2, 3, 4, 5 mM) were employed (entries 2−4), but the
efficiency of the process remained unchanged when either the
biphenyl and DCN combination (entries 5−7) or lower
concentrations of Phen and DCB (entry 8) were utilized.
Finally, employment of a similar ring-opening radical-
cyclization sequence (IV−VI) led to transformation of the
18-membered macrocyclic lactone 4 to the 20-membered
macrocyclic lactam 17 in a high yield (Scheme 5).
Synthesis of Macrocyclic Ketones by Routes Involving
PET-Promoted Cyclization of Carboxylic Acid Tethered
α,β-Unsaturated Ketones. In order to expand the scope of
the new method, an investigation was carried out to explore the
Scheme 4. Preparation of Carboxylic Acid Tethered Acryl
Amide 14
Scheme 5. Synthesis of 17 from 4 by Routes Involving PET-
Promoted Cyclization
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synthesis of macrocyclic ketones from macrocyclic lactones.
Alcohol 2 was prepared from macrocyclic lactone 1 by using
the procedure shown in Scheme 2 (I). PCC oxidation of 2 and
subsequent Grignard reaction of the resulting aldehyde with
vinylmagnesium bromide provided allyl alcohol 18 (VII).
Oxidation of 18 with PCC followed by removal of the MOM
protecting group gave the carboxylic acid tethered α,β-
unsaturated ketone 19 in 42% yield from 1 (I + VII + VIII,
Scheme 6).
Scheme 7. Synthesis of 22 from 4 by Routes Involving PET-
Promoted Cyclization
Scheme 6. Preparation of Carboxylic Acid Tethered α,β-
Unsaturated Ketone 19
mechanism for the PET-promoted decarboxylative intra-
molecular radical cyclization reaction is shown in Scheme 8.
Decarboxylation of the carboxylate ion 23 through single-
electron transfer with the photogenerated radical cation of
Phen produces the alkyl radical 24. When both biphenyl and
DCN are used, the radical cation of biphenyl via PET between
the excited state of DCN and biphenyl is formed, and the
generated radical cation of biphenyl also oxidizes the
carboxylate ion 23 to yield the radical 24 via decarboxylation.
Intramolecular addition of the radical to the α,β-unsaturated
carbonyl group in 24 leads to the formation of the α-carbonyl
radical 25, which subsequently participates in back electron
transfer (BET) with the radical anion of the electron acceptor
to yield the enolate ion precursor of the macrocyclic
photoproduct. In the case of the photoreaction of the
carboxylic acid tethered α,β-unsaturated ketone 19 (X =
CH2), DCN serves as a better electron acceptor than DCB
(Table 3, entries 1, 5−7). The reason for this is likely associated
with the fact that BET from the longer-lived radical anion of
DCN (compared to that of DCB) to the α-carbonyl radical
intermediate 25 occurs more efficiently.7
Irradiation (see above) of an aqueous acetonitrile solution
(CH3CN/H2O = 9:1) of 19 (1 mM) in the presence of NaOH
(1 mM), Phen (20 mM), and DCB (20 mM) gave rise to the
formation of the 16-membered macrocyclic ketone 20 in 52%
yield (entry 1, Table 3). As observed before, when the
Table 3. PET-Promoted Cyclization of Carboxylic Acid 19
a
via Decarboxylation
CONCLUSION
■
In summary, the study described above has led to the
development of a general method for the preparation of
macrocyclic lactones, lactams, and ketones that relies on
cyclization reactions of radical intermediates derived by PET-
promoted decarboxylation of carboxylic acid tethered α,β-
unsaturated carbonyl compounds. The results show that, under
dilute substrate conditions, these processes generate macro-
cyclic photoproducts in high yields. The yields of the
macrocyclic lactone and lactam forming reactions are slightly
dependent on the arene and electron acceptor employed to
initiate the sequential SET pathway. The highest yield of the
macrocyclic ketone forming reaction is achieved by using the
biphenyl and DCN combination. In addition, by utilizing this
method, a 16-membered macrocyclic lactone can be converted
to an 18-membered macrocyclic lactone or lactam, or a 16-
membered macrocyclic ketone, and an 18-membered macro-
cyclic lactone can be converted to a 20-membered macrocyclic
lactone or lactam, or a 18-membered macrocyclic ketone, via
carboxylic acid tethered α,β-unsaturated carbonyl moieties
(Scheme 9). As a result, macrocyclic lactone, lactam, and
ketone products can be prepared with desired ring sizes by
using repetitive cycles of this method. Further investigation of
applications to highly functionalized molecules such as
erythromycin A is currently in progress.
b
entry
19 (mM)
arene
Phen
electron acceptor
DCB
yield of 20 (%)
1
2
3
4
5
6
7
1
2
3
4
1
1
1
1
51
28
16
13
42
76
83
77
Biphenyl
Phen
DCN
Biphenyl
c
8
a
The photoreaction was carried out in the presence of 1 equiv of
NaOH, arenes (20 mM), and electron acceptor (20 mM) using 100-W
high-pressure mercury lamp under an argon atmosphere for 6 h.
b
c
Isolated yield. Concentrations of biphenyl and DCN were 1 mM.
photoreaction was carried out utilizing higher concentrations of
19 (2, 3, 4 mM), the yield of 20 decreased (28, 16, 13%)
(entries 2−4). However, in contrast to photoreactions of 3 and
14, the use of DCN instead of DCB led to an improved yield of
20 (entries 5−8).
In a similar manner, the 18-membered macrocyclic ketone 22
was produced from the 18-membered macrocyclic lactone 4 by
using a seven-step route involving the key PET-promoted
cyclization process (Scheme 7).
EXPERIMENTAL SECTION
■
General Experimental. All reagents and solvents were used as
supplied commercially. 1H NMR spectra were recorded in CDCl3
containing tetramethylsilane as an internal standard, and were acquired
A Plausible Mechanism for PET-Promoted Decarbox-
ylative Intramolecular Radical Cyclization. A plausible
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Scheme 8. Plausible Mechanism for Photodecarboxylative Intramolecular Radical Cyclization
chromatography on silica gel using hexane and EtOAc as eluents
gave the desired MOM-protected compound as a white solid in 92%
yield (3.28 g, 9.2 mmol). Mp 37−38 °C; IR (KBr, cm−1) 2916, 1727;
1H NMR (300 MHz, CDCl3) δ 6.37 (d, J = 17.2 Hz, 1H), 6.09 (dd, J =
17.2, 10.3 Hz, 1H), 5.78 (d, J = 10.3 Hz, 1H), 5.20 (s, 2H), 4.11 (t, J =
6.8 Hz, 2H), 3.43 (s, 3H), 2.32 (t, J = 7.3 Hz, 2H), 1.66−1.57 (m,
4H), 1.23 (m, 20H); 13C NMR (75 MHz, CDCl3) δ 173.3, 166.3,
130.3, 128.6, 90.1, 64.6, 57.5, 34.3, 29.5, 29.5, 29.5, 29.4, 29.4, 29.2,
29.0, 28.5, 25.8, 24.7; HRMS (ESI, m/z) calcd for (M + Na)+
C20H36NaO5, 379.2460; found, 379.2460.
Scheme 9. Ring Expansion of Macrocyclic Lactone and
Conversion to Macrocyclic Lactam and Ketone from
Macrocyclic Lactone
The MOM-protected compound (3.57 g, 10 mmol) was added to a
solution of MgBr2(Et2O) (6.46 g, 25 mmol) in Et2O (50 mL). The
mixture was stirred for 2 h at room temperature and then quenched by
water (50 mL). The product was extracted with Et2O (30 mL × 2),
dried over Na2SO4, and concentrated under reduced pressure.
Purification by column chromatography on silica gel using hexane
and EtOAc as eluents gave the carboxylic acid 3 as a white solid in 97%
yield (3.03 g, 9.7 mmol). Mp 56−57 °C; IR (KBr, cm−1) 3105, 2918,
1723, 1699; 1H NMR (300 MHz, CDCl3) δ 6.38 (d, J = 17.2 Hz, 1H),
6.10 (dd, J = 17.2, 10.3 Hz, 1H), 5.79 (d, J = 10.3 Hz, 1H), 4.13 (t, J =
6.8 Hz, 2H), 2.33 (t, J = 7.3 Hz, 2H), 1.66−1.57 (m, 4H), 1.24 (m,
20H); 13C NMR (75 MHz, CDCl3) δ 179.9, 166.3, 130.4, 128.6, 64.7,
34.0, 29.5, 29.5, 29.5, 29.4, 29.3, 29.2, 29.2, 29.0, 28.5, 25.8, 24.6;
HRMS (ESI, m/z) calcd for (M+Na)+ C18H32NaO4, 335.2198; found,
335.2198.
17-Acryloxylheptadecanoic Acid (5). White solid, mp 64−65 °C;
IR (KBr, cm−1) 3103, 2920, 1724, 1699; 1H NMR (300 MHz, CDCl3)
δ 6.39 (d, J = 17.2 Hz, 1H), 6.11 (dd, J = 17.2, 10.3 Hz, 1H), 5.80 (d, J
= 10.3 Hz, 1H), 4.14 (t, J = 6.8 Hz, 2H), 2.35 (t, J = 7.3 Hz, 2H),
1.68−1.58 (m, 4H), 1.25 (m, 24H); 13C NMR (75 MHz, CDCl3) δ
179.5, 166.3, 130.4, 128.6, 64.7, 33.9, 29.6, 29.6, 29.5, 29.5, 29.4, 29.4,
29.2, 29.2, 29.0, 28.5, 25.9, 24.6; HRMS (ESI, m/z) calcd for (M +
Na)+ C20H36NaO4, 363.2511; found, 363.2511.
on either a 300 or a 500 MHz spectrometer. 13C NMR spectra were
acquired on either a 75 or 125 MHz spectrometer. High resolution
mass spectra were obtained using a time-of-flight mass spectrometer
with a Fourier transform ion cyclotron resonance mass spectrometer
with an ESI positive mode. The light source was a high-pressure
mercury arc.
General Procedure for Synthesis of Macrocyclic Lactones by
Route Involving PET-Promoted Cyclization. Preparation of
Methoxymethyl 15-Hydroxypentadecanate (2). Pentadecalactone 1
(4.81 g, 20 mmol) was added to a solution of KOH (1.68 g, 30 mmol)
in EtOH (80 mL), and the mixture was refluxed for 2 h. The mixture
was evaporated, and the residue was added by hexane and filtered. The
filtrate was dried in vacuo to afford the ring-opening potassium
1
carboxylate as a white solid in a quantitative yield. H NMR (300
MHz, CD3OD) δ 3.52 (t, J = 6.6 Hz, 2H), 2.13 (t, J = 7.5 Hz, 2H),
1.58−1.49 (m, 4H), 1.28 (m, 20H).
16-Acryloxylhexadecanoic Acid (8). White solid, mp 62−63 °C; IR
1
(KBr, cm−1) 3105, 2917, 1723, 1699; H NMR (300 MHz, CDCl3) δ
MOMCl (1.47 mL, 19.5 mmol) was added dropwise to a solution of
the potassium carboxylate (4.44 g, 15 mmol) and pyridine (8 mL) in
DMF (80 mL) at 0 °C under an argon atmosphere. The mixture was
stirred overnight at room temperature, and then water (100 mL) was
added. The product was extracted with EtOAc (30 mL × 3), dried
over Na2SO4, and concentrated under reduced pressure. Purification
by column chromatography on silica gel using hexane and EtOAc as
eluents gave the alcohol 2 as a white solid in 94% yield (4.27 g, 14.1
6.39 (d, J = 17.2 Hz, 1H), 6.11 (dd, J = 17.2, 10.3 Hz, 1H), 5.80 (d, J =
10.3 Hz, 1H), 4.14 (t, J = 6.8 Hz, 2H), 2.34 (t, J = 7.3 Hz, 2H), 1.68−
1.58 (m, 4H), 1.25 (m, 22H); 13C NMR (75 MHz, CDCl3) δ 180.2,
166.4, 130.4, 128.6, 64.7, 34.1, 29.6, 29.5, 29.5, 29.5, 29.4, 29.2, 29.0,
28.6, 25.9, 24.6; HRMS (ESI, m/z) calcd for (M + Na)+ C19H34NaO4,
349.2355; found, 349.2355.
18-Acryloxyloctadecanoic Acid (10). White solid, mp 68 °C; IR
1
(KBr, cm−1) 3103, 2917, 1724, 1699; H NMR (300 MHz, CDCl3) δ
1
mmol). Mp 57 °C; IR (KBr, cm−1) 3274, 2915, 1724; H NMR (300
6.38 (d, J = 17.2 Hz, 1H), 6.11 (dd, J = 17.2, 10.3 Hz, 1H), 5.80 (d, J =
10.3 Hz, 1H), 4.14 (t, J = 6.8 Hz, 2H), 2.34 (t, J = 7.3 Hz, 2H), 1.68−
1.58 (m, 4H), 1.24 (m, 26H); 13C NMR (75 MHz, CDCl3) δ 179.0,
166.4, 130.4, 128.6, 64.7, 33.9, 29.6, 29.6, 29.5, 29.5, 29.5, 29.4, 29.2,
29.2, 29.0, 28.6, 25.9, 24.7; HRMS (ESI, m/z) calcd for (M + Na)+
C21H38NaO4, 377.2668; found, 377.2668.
Photoreaction of Carboxylic Acid Tethered Acrylate Ester.
An aqueous solution (CH3CN 360 mL, H2O 40 mL) of carboxylic acid
3 (125 mg, 1 mM), NaOH (16 mg, 1 mM), Phen (1.43 g, 20 mM),
and DCB (1.28 g, 20 mM) in Pyrex vessels (18 mm × 180 mm) was
purged with argon for 10 min. The mixture was irradiated with a 100-
W high-pressure mercury lamp for 6 h. Then CH3CN was removed
MHz, CDCl3) δ 5.23 (s, 2H), 3.67−3.61 (m, 2H), 3.46 (s, 3H), 2.35
(t, J = 7.3 Hz, 2H), 1.64−1.56 (m, 4H), 1.25 (m, 20H); 13C NMR (75
MHz, CDCl3) δ 173.3, 90.2, 63.1, 57.6, 34.4, 32.8, 29.6, 29.5, 29.4,
29.3, 29.1, 25.7, 24.8; HRMS (ESI, m/z) calcd for (M + Na)+
C17H34NaO4, 325.2355; found, 325.2355.
Preparation of 15-Acryloxylpentadecanoic Acid (3). Acryloyl
chloride (0.98 mL, 12 mmol) was added dropwise to a solution of the
alcohol 2 (3.03 g, 10 mmol) and Et3N (5 mL) in CH2Cl2 (50 mL) at 0
°C under an argon atmosphere. The mixture was stirred for 2 h at
room temperature, and water (50 mL) was added. The product was
extracted with CH2Cl2 (30 mL × 2), dried over Na2SO4, and
concentrated under reduced pressure. Purification by column
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under reduced pressure, and the resulting aqueous solution was
extracted with EtOAc, dried over MgSO4, and concentrated under
reduced pressure. Purification by silica gel column chromatography
using hexane and EtOAc as eluents gave macrocyclic lactone 4 as a
colorless oil in 84% yield. Compound 4 has been previously reported.8
IR (neat, cm−1) 2925, 1734; 1H NMR (300 MHz, CDCl3) δ 4.10 (t, J
= 6.3 Hz, 2H), 2.31 (t, J = 7.1 Hz, 2H), 1.65−1.60 (m, 4H), 1.24 (m,
20H); 13C NMR (75 MHz, CDCl3) δ 173.9, 64.1, 34.7, 28.5, 28.2,
28.2, 28.1, 27.7, 27.2, 27.1, 26.8, 26.6, 26.2, 25.3, 25.0; GC-MS m/z
268 (M+).
under high vacuum with heating (water bath, 60 °C). Purification by
column chromatography on silica gel using hexane and EtOAc as
eluents gave azide as a colorless oil in 90% yield (2.68 g, 9.0 mmol). IR
1
(KBr, cm−1) 2926, 2854, 2096, 1742; H NMR (500 MHz, CDCl3) δ
3.67 (s, 3H), 3.25 (t, J = 7.0 Hz, 2H), 2.30 (t, J = 7.6 Hz, 2H), 1.65−
1.57 (m, 4H), 1.25 (m, 20H). 13C NMR (125 MHz, CDCl3) δ 174.3,
51.4, 34.1, 29.6, 29.6, 29.5, 29.5, 29.4, 29.3, 29.2, 28.9, 26.7, 25.0.
Azide (1.49 g, 5.0 mmol) was added to a solution of PPh3 (1.70 g,
6.5 mmol) in THF (50 mL) under an argon atmosphere, and the
mixture was stirred at room temperature. After 1 day of stirring, water
(10 mL) was added to the solution, and the mixture was stirred for 1
day at room temperature under an argon atmosphere. Then a 1% HCl
aqueous solution (25 mL) was added to the resulting mixture, and
THF and H2O were removed by distillation under high vacuum with
heating (water bath, 40 °C). Purification by column chromatography
on silica gel using CH2Cl2 and MeOH as eluents gave the amine
hydrochloride of 13 as a white solid in 89% yield (1.37 g, 4.9 mmol).
Mp 163−164 °C; IR (KBr, cm−1) 3303, 2916, 2849, 2096, 1732, 1655,
1558; 1H NMR (500 MHz, CDCl3) δ 8.28 (m, 3H), 3.67 (s, 3H), 2.97
(t, J = 7.6 Hz, 2H), 2.30 (t, J = 7.6 Hz, 2H), 1.76 (m, 2H), 1.61 (m,
4H), 1.25 (m, 18H). 13C NMR (125 MHz, CDCl3) δ 174.3, 51.4, 40.0,
34.1, 29.6, 29.6, 29.5, 29.4, 29.3, 29.2, 29.0, 27.7, 26.5, 25.0; HRMS
(ESI, m/z) calcd for (M + H)+ C16H34NO2, 272.2590; found,
272.2591.
Oxacycloeicosan-2-one (6). Compound 6 has been previously
9
1
reported. Colorless oil; IR (neat, cm−1) 2925, 1734; H NMR (300
MHz, CDCl3) δ 4.09 (t, J = 6.2 Hz, 2H), 2.30 (t, J = 7.1 Hz, 2H),
1.64−1.59 (m, 4H), 1.29 (m, 24H); 13C NMR (75 MHz, CDCl3) δ
173.9, 64.2, 34.6, 28.5, 28.5, 28.4, 28.4, 28.4, 28.2, 28.0, 27.8, 27.8,
27.5, 27.3, 27.2, 27.1, 27.0, 25.7, 25.0; GC-MS m/z 296 (M+).
Oxacyclononadecan-2-one (9). Compound 9 has been previously
reported.4b Colorless oil; IR (neat, cm−1) 2925, 1734; H NMR (300
1
MHz, CDCl3) δ 4.11 (t, J = 6.3 Hz, 2H), 2.31 (t, J = 7.1 Hz, 2H),
1.67−1.60 (m, 4H), 1.30 (m, 22H); 13C NMR (75 MHz, CDCl3) δ
174.1, 64.3, 34.6, 28.7, 28.6, 28.6, 28.5, 28.5, 28.3, 27.7, 27.7, 27.6,
27.5, 27.5, 27.4, 26.7, 25.8, 25.0; GC-MS m/z 282 (M+).
Oxacycloheneicosan-2-one (11). Compound 11 has been
previously reported.2d Colorless oil; IR (neat, cm−1) 2925, 1734; H
1
Preparation of 15-Acrylamidepentadecanoic Acid (14). Acryloyl
chloride (0.53 mL, 6.5 mmol) was added dropwise to a solution of
amine hydrochloride of 13 (1.54 g, 5.0 mmol) and ethyldiisopropyl-
amine (2.4 mL, 15 mmol) in CH2Cl2 (40 mL) at 0 °C under an argon
atmosphere. The mixture was stirred for 4 h at 0 °C and quenched by
a 1% HCl aqueous solution (50 mL). The product was extracted with
CH2Cl2 (30 mL × 3), dried over MgSO4, and concentrated under
reduced pressure. Purification by column chromatography on silica gel
using CH2Cl2 and MeOH as eluents gave the acryl amide as a white
solid in 93% yield (1.51 g, 4.65 mmol). Mp 80−81 °C; IR (KBr, cm−1)
3039, 2915, 2850, 1732, 1726; 1H NMR (500 MHz, CDCl3) δ 6.28 (d,
J = 15.6 Hz, 1H), 6.08 (dd, J = 17.0, 10.5 Hz, 1H), 5.64 (d, J = 10.3
Hz, 1H), 5.53 (m, 1H), 3.67 (s, 3H), 3.32 (m, 2H), 2.30 (t, J = 7.6 Hz,
2H), 1.60 (m, 2H), 1.53 (m, 2H), 1.25 (m, 20H). 13C NMR (125
MHz, CDCl3) δ 174.4, 165.5, 131.1, 126.0, 51.4, 39.7, 34.2, 29.6, 29.6,
29.5, 29.4, 29.3, 29.3, 29.2, 27.0, 25.0; HRMS (ESI, m/z) calcd for (M
+ Na)+ C19H35NNaO3, 348.2515; found, 348.2515.
Acryl amide (1.63 g, 5.0 mmol) was dissolved in 3 M NaOH
aqueous solution (1,4-dioxane 50 mL, H2O 20 mL). The mixture was
stirred overnight at room temperature and neutralized by a 10% HCl
aqueous solution. The mixture was evaporated, and the residual
aqueous phase was extracted with EtOAc (30 mL × 3), dried over
MgSO4, and concentrated under reduced pressure. Purification by
column chromatography on silica gel using CH2Cl2 and MeOH as
eluents gave carboxylic acid 14 as a white solid in a quantitative yield
(1.56 g, 5.0 mmol). Mp 103−104 °C; IR (KBr, cm−1) 3305, 3052,
2920, 2850, 1699, 1654, 1624, 1539, 1474; 1H NMR (500 MHz,
CDCl3) δ 6.27 (d, J = 15.6 Hz, 1H), 6.08 (dd, J = 17.1, 10.4 Hz, 1H),
5.65 (m, 1H), 5.64 (d, J = 10.3 Hz, 1H), 3.33 (m, 2H), 2.35 (t, J = 7.5
Hz, 2H), 1.65 (m, 2H), 1.53 (m, 2H), 1.28 (m, 20H). 13C NMR (125
MHz, CDCl3) δ 178.7, 165.7, 130.9, 126.3, 39.7, 34.0, 29.6, 29.5, 29.5,
29.3, 29.3, 29.2, 29.0, 26.9, 24.7. HRMS (ESI, m/z) calcd for (M +
Na)+ C18H33NNaO3, 334.2358; found, 334.2358.
NMR (300 MHz, CDCl3) δ 4.10 (t, J = 6.3 Hz, 2H), 2.30 (t, J = 7.1
Hz, 2H), 1.66−1.58 (m, 4H), 1.29 (m, 26H); 13C NMR (75 MHz,
CDCl3) δ 174.0, 64.3, 34.6, 28.9, 28.8, 28.7, 28.6, 28.6, 28.3, 28.3, 28.2,
27.8, 27.7, 27.7, 27.6, 27.5, 25.9, 25.0; GC-MS m/z 310 (M+).
General Procedure for Synthesis of Macrocyclic Lactams by
Route Involving PET-Promoted Cyclization. Preparation of
Methyl 15-Hydroxypentadecanate (12). Pentadecalactone 1 (4.81
g, 20 mmol) was added to a solution of KOH (1.68 g, 30 mmol) in
EtOH (80 mL), and the mixture was refluxed for 2 h. After removal of
solvent in vacuo, the residue was added by hexane and filtered. The
filtrate was dried in vacuo to give the ring-opening potassium
carboxylate as a white solid in a quantitative yield.
Methyl iodide (6.2 mL, 100 mmol) and sodium bicarbonate (3.36 g,
40 mmol) were added to a solution of the potassium carboxylate (5.92
g, 20 mmol) in DMF (200 mL) at 0 °C under an argon atmosphere.
After stirring at room temperature for 12 h, the mixture was quenched
by water (100 mL), and the product was extracted with EtOAc (50 mL
× 3). The combined organic layer was dried over MgSO4 and
concentrated under reduced pressure. Purification by column
chromatography on silica gel using hexane and EtOAc as eluents
gave 12 as a white solid in 94% yield (5.12 g, 18.8 mmol). Mp 52 °C;
IR (KBr, cm−1) 3291, 2918, 2849, 1741; 1H NMR (500 MHz, CDCl3)
δ 3.66 (s, 3H), 3.65−3.60 (m, 2H), 2.30 (t, J = 7.6 Hz, 2H), 1.62−1.55
(m, 4H), 1.25 (m, 20H). 13C NMR (125 MHz, CDCl3) δ 174.4, 63.0,
51.4, 34.2, 34.1, 32.8, 29.7, 29.6, 29.6, 29.5, 29.5, 29.4, 29.3, 29.3, 29.2,
25.8, 25.1, 25.0; HRMS (ESI, m/z) calcd for (M+Na)+ C16H32NaO3,
295.2249; found, 295.2249.
Preparation of Methyl 15-Aminopentadecanate (13). Methane-
sulfonyl chloride (1.6 mL, 20 mmol) was added dropwise to a solution
of the alcohol 12 (2.72 g, 10 mmol) and Et3N (2.8 mL, 20 mmol) in
THF (50 mL) at 0 °C under an argon atmosphere. The mixture was
stirred for 12 h at room temperature and quenched by water (50 mL).
The product was extracted with EtOAc (30 mL × 3), dried over
MgSO4, and concentrated under reduced pressure. Purification by
column chromatography on silica gel using hexane and EtOAc as
eluents gave mesyl ether as a white solid in 97% yield (3.40 g, 9.7
mmol). Mp 72 °C; IR (KBr, cm−1) 3017, 2915, 2848, 1738, 1343,
17-Acrylamideheptadecanoic Acid (16). White solid, mp 109−110
°C; IR (KBr, cm−1) 3305, 3055, 2919, 2850, 1697, 1654, 1623, 1539,
1472; 1H NMR (500 MHz, CDCl3) δ 6.28 (d, J = 15.6 Hz, 1H), 6.08
(dd, J = 17.1, 10.3 Hz, 1H), 5.63 (d, J = 10.3 Hz, 1H), 5.53 (m, 1H),
3.33 (m, 2H), 2.35 (t, J = 7.6 Hz, 2H), 1.64 (m, 2H), 1.54 (m, 2H),
1.28 (m, 24H). 13C NMR (125 MHz, CDCl3) δ 178.7, 165.7, 130.9,
126.3, 39.7, 34.0, 29.6, 29.4, 29.3, 29.3, 29.2, 29.0, 26.9, 24.7; HRMS
(ESI, m/z) calcd for (M + Na)+ C20H37NNaO3, 362.2671; found,
362.2671.
Photoreaction of Carboxylic Acids Tethered Acryl Amide.
An aqueous solution (CH3CN 360 mL, H2O 40 mL) of carboxylic acid
14 (125 mg, 1 mM), NaOH (16 mg, 1 mM), Phen (1.43 g, 20 mM),
and DCB (1.28 g, 20 mM) in Pyrex vessels (18 mm × 180 mm) was
1
1175, 986, 948, 856; H NMR (500 MHz, CDCl3) δ 4.23 (t, J = 6.7
Hz, 2H), 3.67 (s, 3H), 3.01 (s, 3H), 2.30 (t, J = 7.6 Hz, 2H), 1.76−
1.72 (m, 2H), 1.62 (m, 2H), 1.25 (m, 18H). 13C NMR (125 MHz,
CDCl3) δ 174.4, 70.2, 51.4, 37.4, 34.1, 29.6, 29.6, 29.5, 29.4, 29.4, 29.3,
29.1, 29.0, 25.4, 25.0; HRMS (ESI, m/z) calcd for (M + Na)+
C17H34NaO5S, 373.2025; found, 373.2025.
Mesyl ether (3.51 g, 10 mmol) and NaN3 (0.85 g, 13 mmol) in
DMSO (50 mL) were stirred for 12 h at 80 °C. After the mixture
cooled to room temperature, DMSO was removed by distillation
F
dx.doi.org/10.1021/jo3024126 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
purged with argon for 10 min. The mixture was irradiated with a 100-
W high-pressure mercury lamp for 6 h. Then CH3CN was removed
under reduced pressure, and the resulting aqueous solution was
extracted with EtOAc, dried over MgSO4, and concentrated under
reduced pressure. Purification by silica gel column chromatography
using hexane and EtOAc as eluents gave macrocyclic lactam 15 as a
white solid in 78% yield (80.2 mg, 0.3 mmol). Mp 118 °C; IR (KBr,
cm−1) 3308, 2929, 2851, 1646, 1559, 1459, 722; 1H NMR (500 MHz,
CDCl3) δ 5.65 (m, 1H), 3.30 (m, 2H), 2.16 (t, J = 6.8 Hz, 2H), 1.64
(m, 2H), 1.50 (m, 2H), 1.25 (m, 20H). 13C NMR (125 MHz, CDCl3)
δ 173.1, 39.2, 37.0, 29.4, 29.0, 28.8, 28.8, 28.6, 28.5, 28.3, 28.1, 28.0,
27.9, 27.4, 27.3, 27.1, 27.1, 26.4, 25.9; HRMS (ESI, m/z) calcd for (M
+ Na)+ C17H33NNaO, 290.2460; found, 290.2460.
Azacycloeicosan-2-one (17). White solid, mp 101 °C; IR (KBr,
cm−1) 3305, 2932, 2851, 1646, 1559, 1460, 724; 1H NMR (500 MHz,
CDCl3) δ 5.41 (m, 1H), 3.29 (m, 2H), 2.17 (t, J = 6.7 Hz, 2H), 1.64
(m, 2H), 1.50 (m, 2H), 1.25 (m, 24H). 13C NMR (125 MHz, CDCl3)
δ 173.1, 39.2, 37.0, 29.4, 28.8, 28.8, 28.6, 28.5, 28.3, 28.1, 28.0, 27.9,
27.9, 27.4, 27.3, 27.1, 27.1, 26.4, 25.9; HRMS (ESI, m/z) calcd for (M
+ Na)+ C19H37NNaO, 318.2773; found, 318.2773.
was stirred for 2 h at room temperature and quenched by water (50
mL). The product was extracted with EtOAc (30 mL × 3), dried over
MgSO4, and concentrated under reduced pressure. Purification by
column chromatography on silica gel using hexane and EtOAc as
eluents gave carboxylic acid 19 as a white solid in 97% yield (0.28 g,
0.97 mmol). Mp 63−64 °C; IR (KBr, cm−1) 3049, 2912, 2850, 1712,
1
1696, 1472; H NMR (500 MHz, CDCl3) δ 6.36 (dd, J = 17.6, 10.3
Hz, 1H), 6.21 (d, J = 17.6 Hz, 1H), 5.82 (d, J = 10.3 Hz, 1H), 2.58 (t, J
= 7.3 Hz, 2H), 2.35 (t, J = 7.3 Hz, 2H), 1.61 (m, 4H), 1.26 (m, 18H).
13C NMR (125 MHz, CDCl3) δ 201.2, 179.5, 136.6, 127.9, 39.7, 34.0,
29.5, 29.4, 29.4, 29.2, 29.2, 29.0, 24.7, 24.0; HRMS (ESI, m/z) calcd
for (M + Na)+ C17H30NaO3, 305.2093; found, 305.2093.
17-Oxo-nonadec-18-enoic Acid (21). White solid, mp 70−71 °C;
1
IR (KBr, cm−1) 3075, 2912, 2852, 1716, 1695, 1471; H NMR (500
MHz, CDCl3) δ 6.35 (dd, J = 17.6, 10.3 Hz, 1H), 6.22 (d, J = 17.6 Hz,
1H), 5.81 (d, J = 10.3 Hz, 1H), 2.58 (t, J = 7.3 Hz, 2H), 2.35 (t, J = 7.3
Hz, 2H), 1.62 (m, 4H), 1.26 (m, 22H). 13C NMR (125 MHz, CDCl3)
δ 201.3, 179.8, 136.6, 127.9, 39.6, 34.0, 29.5, 29.5, 29.5, 29.4, 29.4,
29.3, 29.2, 29.2, 29.1, 29.0, 24.6, 24.0; HRMS (ESI, m/z) calcd for (M
+ Na)+ C19H34NaO3, 333.2406; found, 333.2406.
Photoreaction of Carboxylic Acid Tethered α,β-Unsaturated
Ketone. An aqueous solution (CH3CN 360 mL, H2O 40 mL) of
carboxylic acid 19 (113 mg, 1 mM), NaOH (16 mg, 1 mM), biphenyl
(1.43 g, 20 mM), and DCN (1.43 g, 20 mM) in Pyrex vessels (18 mm
× 180 mm) was purged with argon for 10 min. The mixture was
irradiated with a 100-W high-pressure mercury lamp for 6 h. Then
CH3CN was removed under reduced pressure, and the resulting
aqueous solution was extracted with EtOAc, dried over MgSO4, and
concentrated under reduced pressure. Purification by silica gel column
chromatography using hexane and EtOAc as eluents gave macrocyclic
ketone 20 as a colorless oil in 83% yield (95.4 mg, 0.33 mmol).
Compound 20 has been previously reported.2d IR (neat, cm−1) 2927,
General Procedure for Synthesis of Macrocyclic Ketones by
Route Involving PET-Promoted Cyclization. Preparation of
Methoxymethyl 15-Hydroxy-heptadec-16-enate (18). Alcohol 2
(1.51 g, 5.0 mmol) was added to a solution of pyridium
chlorochromate (PCC, 1.51 g, 7 mmol) in CH2Cl2 (20 mL) at 0 °C
under an argon atmosphere. The mixture was stirred for 4 h at 0 °C,
diluted with CH2Cl2, and decanted off three times. The resulting
solution was concentrated under reduced pressure. Purification by
silica gel column chromatography on silica gel using hexane and
EtOAc as eluents gave aldehyde as a white solid in 87% yield (1.31 g,
1
4.35 mmol). Mp 58−59 °C; IR (KBr, cm−1) 2913, 2849, 1738; H
NMR (500 MHz, CDCl3) δ 9.77 (s, 1H), 5.23 (s, 2H), 3.47 (s, 3H),
2.43 (t, J = 7.1 Hz, 2H), 2.36 (t, J = 7.5 Hz, 2H), 1.63 (m, 4H), 1.26
(m, 18H). 13C NMR (125 MHz, CDCl3) δ 202.9, 173.4, 90.1, 57.5,
43.9, 34.3, 29.5, 29.5, 29.4, 29.4, 29.3, 29.2, 29.1, 24.8, 22.1; HRMS
(ESI, m/z) calcd for (M + Na)+ C17H32NaO4, 323.2198; found,
323.2199.
1
2856, 1714; H NMR (500 MHz, CDCl3) δ 2.41 (t, J = 6.7 Hz, 4H),
1.64−1.61 (m, 4H), 1.30 (m, 22H). 13C NMR (125 MHz, CDCl3) δ
212.5, 42.0, 27.6, 27.2, 27.0, 26.5, 26.5, 23.4; GC-MS m/z 239 (M+).
Cyclooctadecanone (22). Compound 22 has been previously
reported.4a Colorless oil; IR (neat, cm−1) 2925, 2854, 1714; 1H NMR
(500 MHz, CDCl3) δ 2.41 (t, J = 6.8 Hz, 4H), 1.64−1.61 (m, 4H),
1.31 (m, 26H). 13C NMR (125 MHz, CDCl3) δ 212.2, 42.3, 28.2, 28.1,
28.0, 27.9, 27.9, 27.8, 27.7, 27.6, 27.2, 27.0, 26.5, 26.7, 23.5; GC-MS
m/z 267 (M+).
Vinylmagnesium bromide (6.5 mL, 1 M in THF solution) was
added dropwise to a solution of aldehyde (1.51 g, 5.0 mmol) in THF
(50 mL) at 0 °C under an argon atmosphere. The mixture was stirred
for 2 h at 0 °C and quenched by a sat. NH4Cl aqueous solution (50
mL). The product was extracted with EtOAc (30 mL × 3), dried over
MgSO4, and concentrated under reduced pressure. Purification by
column chromatography on silica gel using hexane and EtOAc as
eluents gave allyl alcolol 18 as a white solid in 75% yield (1.23 g, 3.75
mmol). Mp 33 °C; IR (KBr, cm−1) 3447, 2931, 2853, 1747, 1646,
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra data for all new compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
1
1466; H NMR (500 MHz, CDCl3) δ 5.93−5.82 (m, 1H), 5.24 (s,
2H), 5.22 (d, J = 17.2 Hz, 1H), 5.10 (d, J = 10.3 Hz, 1H), 4.09 (m,
1H), 3.46 (s, 3H), 2.35 (t, J = 7.3 Hz, 2H), 1.67−1.47 (m, 4H), 1.25
(m, 20H). 13C NMR (125 MHz, CDCl3) δ 173.4, 141.4, 114.5, 90.2,
73.3, 57.5, 37.1, 34.4, 29.6, 29.6, 29.6, 29.4, 29.3, 29.1, 25.3, 25.0, 24.8;
HRMS (ESI, m/z) calcd for (M + Na)+ C19H36NaO4, 351.2511;
found, 351.2511.
AUTHOR INFORMATION
Corresponding Author
*E-mail: yyoshimi@u-fukui.ac.jp.
■
Notes
Preparation of 15-Oxo-heptadec-16-enoic acid (19). Alcohol 18
(0.66 g, 2.0 mmol) was added to a solution of PCC (1.51 g, 7 mmol)
in CH2Cl2 (5 mL) at 0 °C under an argon atmosphere. The mixture
was stirred for 4 h at 0 °C, diluted with CH2Cl2, and decanted off three
times. The resulting solution was concentrated under reduced
pressure. Purification by silica gel column chromatography using
hexane and EtOAc as eluents gave α,β-unsaturated ketone as a white
solid in 70% yield (0.46 g, 1.40 mmol). Mp 42−43 °C; IR (KBr, cm−1)
2926, 2854, 1743, 1712; 1H NMR (500 MHz, CDCl3) δ 6.36 (dd, J =
17.7, 10.3 Hz, 1H), 6.21 (d, J = 17.6 Hz, 1H), 5.81 (d, J = 10.3 Hz,
1H), 5.23 (s, 2H), 3.46 (s, 3H), 2.58 (t, J = 7.3 Hz, 2H), 2.35 (t, J =
7.5 Hz, 2H), 1.67−1.58 (m, 4H), 1.25 (m, 18H). 13C NMR (125
MHz, CDCl3) δ 201.0, 173.3, 136.5, 127.7, 90.1, 57.4, 39.6, 34.2, 29.5,
29.4, 29.3, 29.3, 29.2, 29.0, 24.7, 23.9; HRMS (ESI, m/z) calcd for (M
+ Na)+ C19H34NaO4, 349.2355; found, 349.2354.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by Takahashi Industrial and
Economic Research Foundation, Japan, and the Sasagawa
Scientific Research Grant from the Japan Science Society.
REFERENCES
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