A Total Synthesis of (±)-Rhododaurichromanic Acid A via an Oxa-[3+3] Annulation of Resorcinols

Article abstract of DOI:10.1055/s-0034-1380429

Development of an oxa-[3+3] annulation of vinyliminium salts with resorcinols as a 1,3-diketo equivalent is described. This annulation constitutes a cascade of Knoevenagel condensation-oxa-electrocyclization leading to a direct access to chromenes. A series of attempts was made to demonstrate its synthetic utility in natural product synthesis, culminating in a total synthesis of (±)-rhododaurichromanic acid A that also featured an intramolecular Gassman-type cationic [2+2] cycloaddition.

Full text of DOI:10.1055/s-0034-1380429

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2015, 47, 2713–2720
2713
special topic
G.-Y. Luo et al.
Special Topic
Synthesis
A Total Synthesis of (±)-Rhododaurichromanic Acid A via an
Oxa-[3+3] Annulation of Resorcinols
Guo-Ying Luoa
Hao Wua
OH
OH
R1
X
NHR2
R1
Knoevenagel
Yu Tang*a
Hui Lia,b
Hyun-Suk Yeomb,c
Ka Yanga,b
Richard P. Hsung*b
R
O
H
R
O
1-oxatrienes
resorcinols
oxa-electrocyclization
(
)-rhododauri-
chromanic acid A
OH
R1
H
O
HO
H
a School of Pharmaceutical Science and Technology, Key Laboratory for
Modern Drug Delivery and High-Efficiency, Collaborative Innovation
Center of Chemical Science and Engineering, Tianjin University, Tianjin
300072, P. R. China
HO
H
R
O
an oxa-[3 + 3] with resorcinol
Me
O
yutang@tju.edu.cn
b Division of Pharmaceutical Sciences, School of Pharmacy, and Department
of Chemistry, University of Wisconsin–Madison, Madison, WI 53705, USA
rhsung@wisc.edu
c Korean Research Institute of Chemical Technology, Daejeon, South Korea
Received: 03.04.2015
Accepted after revision: 12.05.2015
Published online: 10.07.2015
details of our studies and a concise total synthesis of (±)-
rhododaurichromanic acid A.
We commenced our study by repeating the reaction
that failed more than a decade earlier. Adding resorcinol 9
to a solution of the vinyliminium salt generated in situ from
citral (10) using 2.0 equivalents of piperidine and 2.0 equiv-
alents of Ac2O followed by heating the mixture at 130 °C for
24 hours led to the desired chromene 11 in 75% isolated
yield (Table 1, entry 1). This success is in direct contrast to
our earlier efforts that somehow had focused on the use of
supposedly more reactive amine salts such as L-proline,16
piperidinium acetate,17 piperidinium trifluoroacetate,10c,18
and ethylenediamine diacetate13 that had proven to be
more successful and operatively versatile in these annula-
tions. Instead, our very original reaction conditions19
proved to be the most effective for this chromene construc-
tion as evident with other examples showcased in Table 1
including one-step syntheses of confluentin 17 (entry 4)
and cannabichromeme 1920 from olivetol 18 (entry 5).
Armed with this success, we embarked on efforts that
could lead to facile total syntheses of chromene natural
products. As shown in Scheme 2, annulation of 6-hydroxy-
indole with citral (10) under the same reactions conditions
leads to 20 in 30% yield. Although the yield is low, it demon-
strates the feasibility of using 1,3-aminohydroxybenzene
(masked here as indole) as a resorcinol equivalent for such
annulation, and that it constitutes a potential facile ap-
proach toward (±)-murrayamine M.21
DOI: 10.1055/s-0034-1380429; Art ID: ss-2015-c0219-st
Abstract Development of an oxa-[3+3] annulation of vinyliminium
salts with resorcinols as a 1,3-diketo equivalent is described. This annu-
lation constitutes a cascade of Knoevenagel condensation–oxa-electro-
cyclization leading to a direct access to chromenes. A series of attempts
was made to demonstrate its synthetic utility in natural product synthe-
sis, culminating in a total synthesis of (±)-rhododaurichromanic acid A
that also featured an intramolecular Gassman-type cationic [2+2] cyc-
loaddition.
Key words oxa-[3+3] annulation, resorcinol, bioinspired total synthe-
sis, (±)-daurichromenic acid, (±)-rhododaurichromanic acid A
One of our longstanding research programs has been
the development of an oxa-[3 + 3] annulation strategy and
its applications.1–4 In particular, annulations of cyclic 1,3-di-
ketones with vinyliminium salts would lead to a facile con-
struction of 1-oxadecalins5 via a sequence of Knoevenagel
condensation–oxa-electrocyclization (1 + 2 → 3 → 4 in
Scheme 1). This tandem sequence constitutes a powerful
cascade6 and represents a bioinspired approach7,8 for natu-
ral product synthesis. While we recognized that an oxida-
tive aromatization of 49,10 would provide an entry into
chromenes 5,11 a far more direct and attractive approach
would be to employ resorcinols 7 in such annulation (7 + 8
→ 6).
In addition, oxidative aromatization of 4 using reagents
such as DDQ proved to be a low-yielding process.9,10 While
elegant reports by Jin12 and later also by Lee,13 Argade,14a
and Zeng14b represent excellent precedents using resorci-
nols in related oxa-annulations, we were able to succeed
such transformation only recently.15 We wish to report here
We next turned to the annulation of 5,7-dihydroxycou-
marin (21), which could be prepared from a ZnCl2-promot-
ed oxa-[3+3] annulation22 of phologlucinol (12) with ethyl
propiolate.23,24 Success here would lead to a facile total syn-
thesis of eriobrucinol.25,26 Instead, annulation of 21 with ci-
tral (10) afforded a complex mixture of double annulated
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2713–2720

2714
G.-Y. Luo et al.
Special Topic
Synthesis
O
O
O
X NHR2
Knoevenagel
R2
+
H
R1
O
H
R1
R2
R1
O
R2
O
1: 1,3-diketones
2: iminium ions
3: 1-oxatrienes
4: oxa-[3+3]
challenging and
low-yielding
[O]
a direct oxa-[3+3] annulation
OH
R2
OH
OH
X NR2
R2
R1
O
H
R1
O
R1
O
R2
7: resorcinols
8
6: R2 = prenyl
5
chromene/chromane natural products
OH
CO2H
O
HO
HO
H
O
HO
H
O
O
HO
H
H
H
O
daurichromenic acid
rhododaurichromanic acid A
hongoquercin A
Scheme 1 A direct approach to chromenes and chromanes
Table 1 Oxa-[3+3] Annulation of Resorcinols
R2
OH
OH
O
piperidine (2.0 equiv)
Ac2O (2.0 equiv)
H
+
R2
toluene
R1
OH
resorcinols
R1
Me
R1
O
enals
Enal
oxa-annulation products
Entry
Resorcinol
R2
Meb
Temp (°C)
Time (h)
Product
Yield (%)a
1
2
3
4
5
9
12
14
9
10
10
15
15
10
130
90
24
18
24
24
40
11
75
93
48
72
50
OHc
H
Meb
13
prenyld
prenyld
Meb
120
120
130
16
Me
17e
19g
f
18
n-C5H11
a All are isolated yields.
b 10: citral.
c 12: phologlucinol.
d 15: trans,trans-farnesal.
e 17: confluentin.
f 18: olivetol.
g 19: cannabichromeme.
product 22 as well as a mixture of single annulation prod-
ucts that we had hoped would include the desired tricycle
25. However, upon treatment of this mixture with TFA at
–30 °C for the ensuing intramolecular Gassman-type cat-
ionic [2+2] cycloaddition that was developed in our
lab,15,27,28 we managed to find only a mixture of iso-eriobru-
cinol A and B in 26% combined yield, and not eriobrucinol,
thereby validating the presence of single annulation prod-
ucts 23 and 24 but not 25 (Scheme 3). A much more suc-
cessful exercise is shown in a synthesis of (±)-daurichrome-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2713–2720

2715
G.-Y. Luo et al.
Special Topic
Synthesis
nic acid29 from confluentin (17) via a short two-step se-
quence (Scheme 4): A regioselective formylation of 17,
which would give aldehyde 26, and a subsequent standard
Lindgren–Pinnick oxidation of 26.
CHO
piperidine
(2.0 equiv)
Ac2O
(2.0 equiv)
with citral (10)
N
O
H
N
To ultimately demonstrate the power of this resorcinol
oxa-[3+3] annulation, we put together a concise total syn-
thesis of (±)-rhododaurichromanic acid A.30,31 As shown in
Scheme 5, under our cationic [2+2]-cycloaddition condi-
tions, chromenes 26 and 17 underwent two completely dif-
ferent reaction pathways. Intriguingly, the former led to
only the tetracyclic manifold 27 via a polyene cyclization
process32 with no observable cationic [2+2] cycloadduct 28,
while the latter gave only the cationic [2+2] cycloadduct 30.
With the only difference between 26 and 17 being the
formyl substitution, this unexpected diverging course actu-
ally sheds light on the mechanism of the cationic [2+2] cyc-
loaddition. The formyl substitution in 26 renders the
chromene oxygen atom (in blue) less Lewis basic than the
corresponding oxygen atom (also in blue) in 17. Conse-
quently, protonation of this oxygen atom in 26 is likely
slower than that in 17, and that a slower protonation would
allow the polyene-cyclization pathway to proceed more fa-
vorably as shown in 27-TS. This outcome would then sug-
gest that protonation of the chromene oxygen atom is es-
O
H
toluene
100 °C, 32 h
H
N
H
HO
H
H
20: 30% murrayamine M
Scheme 2 A possible approach to (±)-murrayamine M
sential for initiating the cationic [2+2] cycloaddition path-
way as shown in 30-TS because of the allyl cation formation
needed for such cycloaddition.
While tetracycle 27 should be very useful for a total
synthesis (±)-hongoquercin A,32–34 we focused on complet-
ing the synthesis of (±)-rhododaurichromanic acid A. As
shown in Scheme 6, the use of Fe(OTf)3 was even more use-
ful for the cationic [2+2] cycloaddition,28 as it does not suf-
fer from the addition of TFA to the terminal prenyl double
bond (see 30 in Scheme 5). Subsequent formylation of 31
and Lindgren–Pinnick oxidation would furnish (±)-rho-
dodaurichromanic acid A.
CO2Et
piperidine (2.0 equiv)
HO
HO
Ac2O (2.0 equiv), citral (10)
ZnCl2, 100 °C
O
toluene, 90 °C, 24 h
HO
OH
O
O
OH
O
O
O
12
21: 73%
and 7–13% of the following possible mixture
22: 4–21%
HO
HO
O
+
and
O
O
O
O
O
O
O
O
OH
23
24
25
TFA-CH2Cl2 (1:5)
–30 °C to r.t., 18 h
HO
H
cationic [2+2]
HO
O
yield: 26% (1:2)
H
H
HO
H
H
O
O
O
O
+
H
H
H
O
O
O
H
O
O
OH
H
iso-eriobrucinol B
iso-eriobrucinol A
eriobrucinol: not found
Scheme 3 An attempt to synthesize (±)-eriobrucinol
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2713–2720

2716
G.-Y. Luo et al.
Special Topic
Synthesis
R1
O
OH
OH
(COCl)2, DMF
H
MeCN, 0 °C to r.t.
O
O
17: R1 = prenyl (confluentin)
NaClO2, NaH2PO4
26: 36%
O
OH
OH
t-BuOH, MeCN, DME
O
yield: 48%
( )-daurichromenic acid
Scheme 4 Synthesis of (±)-daurichromenic acid
R
R
O2CCF3
HO
HO
TFA–CH2Cl2 (1:5)
–78 °C to r.t.
15
15
or
H
HO
1
10
15
5
H
O
O
9
9
1
R
9
5
H
7
5
H
O
26: R = CHO
17: R = H
for R = CHO:
for R = H:
27: 47%
28: not found
30: 35%
29: not found
O2CCF3
CHO
HO
10
15
5
9
H
10
5
9
OH
H
O
15
H
H
H
4
O
H
less Lewis basic
H
H
30-TS: a cationic [2+2] pathway
27-TS: a polyene cyclization pathway
Scheme 5 A substrate dependent diverging cationic pathway
We have described here our efforts in developing an
oxa-[3+3] annulation of vinyliminium salts with resorcinols
as a 1,3-diketo equivalent. This annulation constitutes a
powerful cascade of Knoevenagel condensation–oxa-elec-
trocyclization to directly access chromenes. A series of at-
tempts was made to demonstrate the synthetic utility of
this new annulation in natural product synthesis. An ulti-
mate total synthesis of (±)-rhododaurichromanic acid A
was achieved and featured an intramolecular Gassman-
type cationic [2+2] cycloaddition.
All reactions were performed in flame-dried glassware under N2 at-
mosphere. Solvents were distilled prior to use. Reagents were used as
purchased from J & K, Beijing Ouhe, Aldrich, Acros, Alfa Aesar, or TCI,
unless otherwise noted. Petroleum ether (PE) used refers to the hy-
drocarbon mixture with a boiling range of 60–90 °C. Chromatograph-
1
ic separations were performed using Kangbino 48–75 Å SiO2. H and
13C NMR spectra were recorded on 600 MHz Bruker Avance spectrom-
eters using CDCl3 with TMS or residual solvent as standard, unless
otherwise noted. Melting points were determined using a Laboratory
Devices MEL-TEMP and are uncorrected/calibrated. IR spectra were
recorded on a Bruker TENSOR 27 spectrometer. TLC analysis was per-
formed using Kangbino glass-backed plates (60 Å, 250 μm) and visu-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2713–2720

2717
G.-Y. Luo et al.
Special Topic
Synthesis
1H NMR (600 MHz, CDCl3): δ = 1.37 (s, 3 H), 1.57 (s, 3 H), 1.65 (s, 3 H),
1.67–1.78 (m, 2 H), 2.06–2.14 (m, 2 H), 2.18 (s, 3 H), 5.06–5.10 (m, 1
H), 5.14 (br s, 1 H), 5.47 (d, J = 9.9 Hz, 1 H), 6.09 (s, 1 H), 6.24 (s, 1 H),
6.61 (d, J = 9.9 Hz, 1 H).
13C NMR (150 MHz, CDCl3): δ = 17.7, 21.5, 22.8, 25.7, 26.2, 41.0, 78.3,
106.9, 108.5, 109.8, 116.9, 124.2, 127.2, 131.7, 139.6, 151.1, 154.0.
HO
Fe(OTf)3
(30 mol%)
(COCl)2, DMF
H
HO
H
O
MeCN, 0 °C to r.t.
CH2Cl2, r.t.
MS (APCI): m/z (%) = 281.1 [100, (M + Na)+].
H
HRMS (ESI): m/z (M – H)– calcd for C17H21O2–: 257.1542; found:
O
257.1545.
31: 55%
17
16
Yield: 280 mg (48%); yellow oil; Rf = 0.47 (PE–EtOAc, 9:1).
NaClO2
NaH2PO4
IR (KBr): 3408brs, 2968s, 2923s, 1618s, 1581w, 1505m, 1460m,
H
H
1377w, 1153s, 1117s, 988w cm–1
.
O
HO
O
HO
H
H
t-BuOH
MeCN, DME
1H NMR (600 MHz, CDCl3): δ = 1.37 (s, 3 H), 1.57 (s, 3 H), 1.59 (s, 3 H),
1.67 (s, 3 H), 1.94–1.97 (m, 2 H), 2.04–2.08 (m, 3 H), 2.08–2.15 (m, 3
H), 5.08–5.11 (m, 3 H), 5.41 (d, J = 9.8 Hz, 1 H), 6.29 (s, 3 H), 6.80 (d, J =
7.7 Hz, 1 H).
13C NMR (150 MHz, CDCl3): δ = 16.0, 17.7, 22.6, 25.7, 26.7, 39.7, 41.3,
78.8, 103.5, 107.4, 107.5, 114.7, 116.8, 122.4, 124.0, 124.3, 127.2,
131.4, 135.3, 154.6, 156.5.
H
HO
H
H
O
32: 46%
O
( )-rhododaurichromanic acid A
54%
Scheme 6 A total synthesis of (±)-rhododaurichromanic acid A
MS (APCI): m/z (%) = 335.2 [100, (M + Na)+].
HRMS (ESI): m/z (M + Na)+ calcd for C21H28O2Na+: 335.1987; found:
335.1994.
alized using UV and KMnO4 stains. Low-resolution mass spectra were
obtained using an Agilent 1100 series LS/MSD. High-resolution mass
spectra were obtained using a Q-TOF micro (Bruker) spectrometer.
Confluentin (17)
Yield: 370 mg (72%); brown oil; Rf = 0.45 (PE–EtOAc, 9:1).
Oxa-[3+3] Annulation; Typical Procedure
IR (KBr): 3410brs, 2968s, 2924s, 1626s, 1579s, 1451s, 1376m, 1142m,
To a solution of citral (10; 1.70 mL, 10.0 mmol) and piperidine (2.17
mL, 22.0 mmol) in EtOAc (18 mL) was added Ac2O (2.17 mL, 23.0
mmol) dropwise at 0 °C under a blanket of argon. After addition, the
flask was sealed and the reaction mixture was heated in a 90 °C oil
bath for 1 h. This iminium salt solution was then added to a solution
of phloroglucinol (12; 1.89 g, 15.0 mmol) in toluene (41 mL) dropwise
via cannula at r.t. under argon. The resulting mixture was stirred at
90 °C for 18 h before it was cooled to r.t. and concentrated under re-
duced pressure. The crude residue was purified using silica gel flash
column chromatography (gradient eluent: 10–20% EtOAc in PE) to
give chromene 13 (2.38 g, 93%) as a brown oil; yield: 2.38 g (93%); Rf =
0.50 (hexanes–EtOAc, 2:1) (Table 1).
1075s, 991w cm–1
.
1H NMR (600 MHz, CDCl3): δ = 1.37 (s, 3 H), 1.57 (s, 3 H), 1.59 (s, 3 H),
1.67 (s, 3 H), 1.70–1.78 (m, 2 H), 1.93–1.97 (m, 2 H), 2.02–2.06 (m, 2
H), 2.07–2.13 (m, 2 H), 2.19 (s, 3 H), 4.81 (br s, 1 H), 5.06–5.12 (m, 2
H), 5.49 (d, J = 10.0 Hz, 1 H), 6.10 (s, 1 H), 6.24 (s, 1 H), 6.61 (d, J = 10.1
Hz, 1 H).
13C NMR (150 MHz, CDCl3): δ = 16.0, 17.7, 21.5, 22.7, 25.7, 26.3, 26.7,
39.7, 41.1, 78.3, 106.9, 108.4, 109.8, 116.9, 124.1, 124.4, 127.1, 131.3,
135.3, 139.5, 151.2, 154.1.
MS (APCI): m/z (%) = 348.9 [100, (M + Na)+].
HRMS (ESI): m/z (M – H)– calcd for C22H29O2–: 325.2162; found:
IR (thin film): 3414br s, 2960w, 2918w, 2855w, 1621m, 1580m,
325.2155.
1429m, 1370w, 1343w, 1141m, 1082m, 1048w, 831w cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.37 (s, 3 H), 1.58 (s, 3 H), 1.66 (s, 3 H),
1.54–1.78 (m, 2 H), 2.02–2.16 (m, 2 H), 4.90 (br s, 2 H), 5.09 (t quint,
J = 7.2, 1.4 Hz, 1 H), 5.41 (d, J = 10.1 Hz, 1 H), 5.83 (d, J = 2.4 Hz, 1 H),
5.92 (d, J = 2.3 Hz, 1 H), 6.55 (d, J = 10.1 Hz, 1 H).
Cannabichromene (19)20a
Yield: 260 mg (50%); brown oil; Rf = 0.75 (hexanes–EtOAc, 4:1).
IR (thin film): 3416brs, 2963s, 2928w, 2859w, 1624s, 1576s, 1431m,
1377m, 1343w, 1144w, 1084m, 1053w, 833w cm–1
.
13C NMR (100 MHz, CDCl3): δ = 22.9, 25.9, 26.5, 41.2, 79.0, 95.6, 97.0,
1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 7.0 Hz, 3 H), 1.20–1.36 (m, 4
H), 1.38 (s, 3 H), 1.48–1.62 (m, 2 H), 1.57 (s, 3 H), 1.62–1.83 (m, 2 H),
1.65 (s, 3 H), 2.00–2.21 (m, 2 H), 2.43 (t, J = 7.6 Hz, 2 H), 4.79 (br s, 1
H), 5.00–5.18 (m, 1 H), 5.49 (d, J = 10.0 Hz, 1 H), 6.11 (d, J = 1.0 Hz, 1
H), 6.25 (s, 1 H), 6.61 (d, J = 10.0 Hz, 1 H).
103.4, 116.7, 124.3, 125.6, 131.9, 152.4, 155.6, 156.7.
MS (APCI): m/z (%) = 261.2 [100, (M + H)+].
HRMS (ESI): m/z [M + H]+ calcd for C16H21O3: 261.1485; found
261.1491.
13C NMR (100 MHz, CDCl3): δ = 14.1, 17.7, 22.7, 22.8, 25.8, 26.4, 30.8,
31.6, 36.0, 41.2, 78.3, 107.1, 107.8, 109.3, 116.9, 124.3, 127.4, 131.8,
144.9, 151.1, 154.2.
MS (APCI): m/z (%) = 315.3 [100, (M + H)+].
HRMS (ESI): m/z [M + H]+ calcd for C21H31O2: 315.2319; found:
11
Yield: 390 mg (75%); brown oil; Rf = 0.51 (PE–EtOAc, 9:1).
IR (KBr): 3419br s, 2969m, 2923s, 1625s, 1579w, 1451s, 1142m,
1084s, 1058s, 990w cm–1
.
315.2320.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2713–2720

2718
G.-Y. Luo et al.
Special Topic
Synthesis
20
1H NMR (600 MHz, CDCl3): δ = 1.41 (s, 3 H), 1.57 (s, 3 H), 1.59 (s, 3 H),
1.67 (s, 3 H), 1.75–1.78 (m, 2 H), 1.94–1.96 (m, 2 H), 2.02–2.06 (m, 2
H), 2.08–2.11 (m, 2 H), 2.53 (s, 3 H), 5.08–5.12 (m, 2 H), 5.48 (d, J = 9.9
Hz, 1 H), 6.23 (s, 1 H), 6.73 (d, J = 9.9 Hz, 1H), 11.71 (s, 1 H).
13C NMR (150 MHz, CDCl3): δ = 16.0, 17.7, 22.6, 24.5, 25.7, 26.7, 27.2,
39.7, 41.7, 80.1, 103.5, 107.0, 112.2, 116.7, 123.7, 124.3, 126.3, 131.4,
135.5, 144.4, 159.0, 160.7, 175.8.
Yield: 12 mg (30%); yellow oil; Rf = 0.43 (PE–EtOAc, 9:1).
IR (KBr): 3422brs, 2967s, 2923s, 1641s, 1436s, 1376m, 1173w, 803s,
717s cm–1
.
1H NMR (600 MHz, CDCl3): δ = 1.42 (s, 3 H), 1.57 (s, 3 H), 1.65 (s, 3 H),
1.71–1.76 (m, 2 H), 2.10–2.18 (m, 2 H), 5.08–5.10 (m, 1 H), 5.62 (d, J =
9.8 Hz, 1 H), 6.46 (s, 1 H), 6.59 (d, J = 9.7 Hz, 1 H), 6.67 (d, J = 8.3 Hz, 1
H), 7.08 (s, 1 H), 7.36 (d, J = 8.3 Hz, 1 H), 8.00 (br s, 1 H).
13C NMR (150 MHz, CDCl3): δ = 16.6, 21.7, 24.6, 24.7, 39.5, 76.9, 102.1,
103.7, 109.8, 116.3, 119.7, 121.4, 121.8, 123.2, 127.6, 130.6, 131.3,
147.9.
MS (APCI): m/z (%) = 393.1 [100, (M + Na)+].
HRMS (ESI): m/z (M – H)– calcd for C23H29O4–: 369.2066; found:
369.2062.
Aldehyde 27
MS (APCI): m/z (%) = 268.2 [100, (M + Na)+].
To a solution of the aldehyde 26 (18.0 mg, 0.053 mmol) in CH2Cl2 (5
mL) at –78 °C was added TFA (1 mL, 15 mmol) dropwise. The mixture
was stirred at –78 °C for 1 h and then at r.t. for 2 h. The reaction was
then quenched by pouring the mixture to sat aq NaHCO3 (2 mL) and
the aqueous layer was extracted with EtOAc (3 × 10 mL). The com-
bined organic phases were washed with brine (2 mL), dried (Na2SO4),
and concentrated under reduced pressure. The crude residue was pu-
rified by flash column chromatography (SiO2, 2% EtOAc in PE) to pro-
vide the aldehyde 27 as a yellow oil; yield: 8.2 mg (47%); Rf = 0.70
(PE–EtOAc, 9:1).
HRMS (ESI): m/z (M + H)+ calcd for C18H22NO+: 268.1701; found:
268.1701.
Aldehyde 26
To a solution of DMF (1.0 mL, 5.0 mmol) in MeCN (5 mL) was added
oxalyl chloride (0.50 mL, 4.5 mmol) under a blanket of N2 at 0 °C. The
resulting mixture was stirred for an additional 30 min at 0 °C. A solu-
tion of 17 in MeCN (0.50 mL) was then added dropwise a 0 °C. After
stirring overnight at r.t., the reaction mixture was quenched with 10%
aq NaOH (30 mL) and the aqueous layer was extracted with EtOAc (3
× 30 mL). The combined organic layers were dried (Na2SO4) and con-
centrated under reduced pressure. The crude residue was purified by
flash column chromatography (SiO2, 1% EtOAc in PE) to provide the
aldehyde 26 as a yellow oil; yield: 35 mg (36%); Rf = 0.75 (PE–EtOAc,
9:1).
IR (KBr): 2930s, 1777s, 1632s, 1370m, 1262m, 1219s, 1014m cm–1
.
1H NMR (600 MHz, CDCl3): δ = 0.86 (s, 3 H), 0.92 (s, 3 H), 1.09 (d, J =
12.2 Hz, 1 H), 1.16 (s, 3 H), 1.25–1.28 (m, 2 H), 1.45 (s, 3 H), 1.56–1.60
(m, 2 H), 1.68 (t, J = 12.8 Hz, 2 H), 1.79 (d, J = 13.5 Hz, 1 H), 1.91 (td, J =
4.2, 9.4 Hz, 1 H), 2.03 (d, J = 12.1 Hz, 1 H), 2.19 (d, J = 12.6 Hz, 1 H),
2.49 (s, 3 H), 6.18 (s, 1 H), 6.46 (s, 1 H), 10.06 (s, 1 H), 12.66 (s, 1 H).
13C NMR (150 MHz, CDCl3): δ = 18.3, 18.8, 19.3, 21.7, 23.5, 27.3, 33.3,
33.7, 38.0, 39.4, 41.4, 41.5, 52.2, 80.2, 107.4, 109.0, 110.9, 113.3,
142.7, 149.0, 159.4, 160.4, 193.0.
IR (KBr): 2970s, 2925m, 1633s, 1568m, 1483m, 1451m, 1385m,
1292s, 1252s, 1158s, 839w cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.41 (s, 3 H), 1.56 (s, 3 H), 1.59 (s, 3 H),
1.67 (s, 3 H), 1.74–1.79 (m, 2 H), 1.93–1.97 (m, 2 H), 2.01–2.05 (m, 2
H), 2.06–2.10 (m, 2 H), 2.48 (s, 3 H), 5.06–5.11 (m, 2 H), 5.48 (d, J =
10.1 Hz, 1 H), 6.16 (s, 1 H), 6.69 (d, J = 10.2 Hz, 1 H), 10.03 (s, 1 H),
12.64 (s, 1 H).
MS (APCI): m/z (%) = 376.9 [100, (M + Na)+].
HRMS (ESI): m/z (M – H)– calcd for C23H29O3–: 353.2117; found:
353.2121.
13C NMR (100 MHz, CDCl3): δ = 16.0, 17.7, 18.3, 22.6, 25.7, 26.7, 27.3,
39.7, 41.8, 80.7, 107.0, 111.0, 113.2, 115.8, 123.6, 124.3, 126.3, 131.3,
135.6, 143.7, 160.6, 160.9, 192.8.
MS (APCI): m/z (%) = 377.0 [100, (M + Na)+].
HRMS (ESI): m/z (M + Na)+ calcd for C23H30O3Na+: 377.2093; found:
30
To a solution of confluentin (17; 20.0 mg, 0.072 mmol) in CH2Cl2 (1.2
mL) at –78 °C was added TFA (0.23 mL, 3.00 mmol) dropwise. The
mixture was stirred at –78 °C for 1 h and then at r.t. for 1.5 h. The re-
action was then quenched by pouring the mixture to sat aq NaHCO3
(2 mL) and the aqueous layer was extracted with EtOAc (3 × 5 mL).
The combined organic phases were washed with brine (2 mL), dried
(Na2SO4), and concentrated under reduced pressure. The crude resi-
due was purified by flash column chromatography (SiO2, 2% EtOAc in
PE) to provide compound 30 as a yellow oil; yield: 7 mg (35%); Rf = 0.4
(PE–EtOAc, 9:1).
377.2096.
(±)-Daurichomenic Acid
To a solution of the above aldehyde 26 (17.0 mg, 0.050 mmol) in t-
BuOH (0.6 mL), MeCN (0.6 mL), 2-methylbut-2-ene (0.40 mL), and
1,2-dimethoyethane (0.20 mL) were added NaH2PO4 (28.0 mg, 0.25
mmol) and NaClO2 (22.0 mg, 0.25 mmol, dissolved in 0.2 mL H2O) at
–20 °C. After stirring for an additional 2 h at –20 °C, the mixture was
warmed up slowly to r.t. and stirred overnight. Then, brine (3 mL) was
added and the aqueous layer was extracted with EtOAc (3 × 5 mL).
The combined organic layers were dried (Na2SO4) and concentrated
under reduced pressure. The crude residue was purified via flash col-
umn chromatography (SiO2, gradient eluent: 10–40% EtOAc in PE) to
provide (±)-daurichromenic acid as a yellow oil; yield: 8 mg (48%);
Rf = 0.15 (PE–EtOAc, 1:1).
IR (KBr): 2962s, 1777s, 1585w, 1372m, 1261m, 1218s, 1017s cm–1
.
1H NMR (600 MHz, CDCl3): δ = 0.73 (s, 3 H), 1.36 (s, 3 H), 1.56 (s, 3 H),
1.57 (s, 3 H), 1.62–1.66 (m, 5 H), 1.75 (td, J = 6.9, 18.1 Hz, 2 H), 1.86
(dd, J = 7.6, 8.0 Hz, 2 H), 1.96–1.99 (m, 1 H), 2.22 (s, 3 H), 2.38–2.40
(m, 1 H), 2.56 (t, J = 8.7 Hz, 1 H) 3.04 (d, J = 9.4 Hz, 1 H), 4.48 (br m, 1
H), 6.15 (s, 1 H), 6.32 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 14.9, 18.2, 21.2, 25.5, 25.6, 25.7, 27.2,
35.4, 38.5, 39.0, 41.0, 42.4, 44.4, 46.5, 83.4, 89.4, 108.0, 108.4, 111.4,
114.5 (q, J = 427.9 Hz), 137.5, 153.9, 154.5, 156.3 (q, J = 61.2 Hz).
IR (KBr): 2927s, 1619s, 1454s, 1381w, 1264s, 1177s, 1010m cm–1
.
19F NMR (564 MHz, CDCl3): δ = –75.73.
MS (APCI): m/z (%) = 463.6 [100, (M + Na)+].
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2713–2720

2719
G.-Y. Luo et al.
Special Topic
Synthesis
HRMS (ESI): m/z (M – H)– calcd for C24H30F3O4–: 439.2090; found:
439.2089.
the aqueous layer was extracted with EtOAc (3 × 5 mL). The combined
organic layers were dried (Na2SO4) and concentrated under reduced
pressure. The crude residue was purified by flash column chromatog-
raphy (SiO2, 10–40% EtOAc in PE) to afford (±)-rhododaurichomanic
acid A as a white solid; yield: 8 mg (54%); mp 168–170 °C; Rf = 0.12
(PE–EtOAc, 1:1).
Alkene 31
To a solution of confluentin (17; 50.0 mg, 0.17 mmol) in CH2Cl2 (2 mL)
was added Fe(OTf)3 (25.0 mg, 0.005 mmol) at r.t. under a blanket of
N2. After stirring for 6 h, the reaction mixture was quenched with sat
aq NaHCO3 (2 mL) and the aqueous layer was extracted with CH2Cl2 (3
× 5 mL). The combined organic layers were washed with brine (2 mL),
dried (Na2SO4), and concentrated under reduced pressure. The crude
residue was purified by flash column chromatography (SiO2, 2% EtOAc
in PE) to provide the alkene 31 as white solid; yield: 36 mg (55%); Rf =
0.40 (PE–EtOAc, 9:1); mp 136–138 °C.
IR (KBr): 3410brs, 2962w, 2930m, 1620m, 1572w, 1460s, 1365m cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.76 (s, 3 H), 1.40 (s, 3 H), 1.65 (s, 3 H),
1.65–1.69 (m, 3 H), 1.71 (s, 3 H), 1.86 (t, J = 6.9 Hz, 1 H), 1.89–1.95 (m,
2 H), 1.99–2.14 (m, 2 H), 2.50 (m, 1 H), 2.53 (s, 3 H), 2.58 (t, J = 4.9 Hz,
1 H), 3.11 (d, J = 6.0 Hz, 1 H), 5.18 (t, J = 4.0 Hz, 1 H), 6.30 (s, 1 H),
11.66 (br s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 14.7, 17.6, 22.7, 24.5, 25.7, 25.8, 27.5,
35.5, 38.5, 39.1, 42.3, 44.5, 46.2, 84.5, 103.1, 109.6, 113.7, 125.1,
131.0, 141.7, 159.3, 164.3, 176.2.
IR (KBr): 1450w, 1260s, 1089m, 1017s cm–1
.
1H NMR (600 MHz, CDCl3): δ = 0.76 (s, 3 H), 1.36 (s, 3 H), 1.63 (s, 3 H),
1.58–1.63 (m, 2 H), 1.66 (d, J = 5.6 Hz, 1 H), 1.70 (s, 3 H), 1.71–1.76 (m,
2 H), 1.93–1.99 (m, 2 H), 2.03–2.07 (m, 1 H), 2.22 (s, 3 H), 2.47 (t, J =
6.5 Hz, 1 H), 2.56 (t, J = 7.9 Hz, 1 H), 3.05 (d, J = 9.5 Hz, 1 H), 4.43 (br s,
1 H), 5.17 (t, J = 6.8 Hz, 1 H), 6.17 (s, 1 H,), 6.32 (s, 1 H).
MS (APCI): m/z (%) = 392.9 [100, (M + Na)+].
HRMS (ESI): m/z (M – H)– calcd for C23H29O4–: 369.2066; found:
369.2069.
13C NMR (150 MHz, CDCl3): δ = 14.9, 17.6, 21.2, 22.8, 25.5, 25.8, 27.3,
35.4, 38.4, 38.9, 42.3, 44.3, 46.7, 83.4, 108.0, 108.4, 111.3, 124.9,
131.3, 137.5, 153.9, 154.4.
Acknowledgment
MS (APCI): m/z (%) = 349.7 [100, (M + Na)+].
HRMS (ESI): m/z (M – H)– calcd for C22H29O2–: 325.2162; found:
G.Y.L. and H.W. contributed equally to this work. R.P.H. thanks NSF
(CHE1012198) for general support. Y.T. thanks the National Natural
Science Foundation of China (Nos. 21172169 and 21172168) and The
National Basic Research Project (No. 2014CB932201) for generous
funding. Service from The Instrumentation Center at School of Phar-
maceutical Science and Technology of Tianjin University is greatly ap-
preciated.
325.2161.
Aldehyde 32
To a solution of DMF (0.70 mL, 8.69 mmol) in MeCN (20 mL) was add-
ed oxalyl chloride (0.60 mL, 7.10 mmol) under a blanket of N2 and
stirred for 30 min at 0 °C. A solution of alkene 31 (255.0 mg, 0.79
mmol) in MeCN (10 mL) was then added dropwise at 0 °C. After stir-
ring overnight at r.t., the reaction mixture was quenched with 10% aq
NaOH (20 mL) and the aqueous layer was extracted with EtOAc (3 ×
30 mL). The combined organic layers were dried (Na2SO4) and con-
centrated under reduced pressure. The crude residue was purified by
flash column chromatography (SiO2, 2% EtOAc in PE) to provide the al-
dehyde 32 as a white solid; yield: 113 mg (46%); Rf = 0.78 (PE–EtOAc,
9:1); mp 118–120 °C.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380429.
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
References
(1) For reviews on oxa-[3+3] annulations, see: (a) Harrity, J. P. A.;
Provoost, O. Org. Biomol. Chem. 2005, 3, 1349. (b) Hsung, R. P.;
Kurdyumov, A. V.; Sydorenko, N. Eur. J. Org. Chem. 2005, 23.
(c) Hsung, R. P.; Cole, K. P. Strategies and Tactics in Organic Syn-
thesis; Pergamon: Oxford, 2004, 41. (d) Deng, J.; Wang, X.-N.;
Hsung, R. P. A Formal [3+3] Cycloaddition Approach to Natural
Product Synthesis, In Methods and Applications of Cycloaddition
Reactions in Organic Syntheses; Nishiwaki, N., Ed.; Wiley-VCH:
Weinheim, 2014, Chap. 12.
(2) For recent reviews on [3+3] cycloadditions, see: (a) Xu, X.;
Doyle, M. P. Acc. Chem. Res. 2014, 47, 1396. (b) Moyano, A.; Rios,
R. Chem. Rev. 2011, 111, 4703.
(3) For recent development and applications employing oxa-[3+3]
annulations, see: (a) Fotiadou, A. D.; Zografos, A. L. Org. Lett.
2012, 14, 5664. (b) Hu, J.; Dong, W.; Wu, X.-Y.; Tong, X. Org. Lett.
2012, 14, 5530. (c) dos Santos, W. H.; da Silva-Filho, L. C. Synthe-
sis 2012, 44, 3361. (d) Lee, Y. R.; Pandit, R. P. Synthesis 2012, 44,
2910. (e) Parker, K. A.; Thomas, L.; Mindt, T. L. Tetrahedron 2011,
67, 9779.
IR (KBr): 2962w, 1625s, 1578m, 1489m, 1371s, 1261s, 1017s cm–1
.
1H NMR (600 MHz, CDCl3): δ = 0.76 (s, 3 H), 1.39 (s, 3 H), 1.57–1.63
(m, 2 H), 1.64 (s, 3 H), 1.65–1.69 (m, 2 H), 1.71 (s, 3 H), 1.72–1.76 (m,
1 H), 1.85 (t, J = 11.6 Hz, 1 H), 1.89–1.93 (m, 2 H), 2.07–2.16 (m, 1 H),
2.48 (s, 3 H), 2.57 (t, J = 6.8 Hz, 1 H), 3.09 (d, J = 9.2 Hz, 1 H), 5.18 (t, J =
7.62 Hz, 1 H), 6.23 (s, 1 H), 10.05 (s, 1 H), 12.59 (s, 1 H).
13C NMR (150 MHz, CDCl3): δ = 14.7, 17.7, 18.0, 22.7, 25.7, 25.8, 27.4,
34.8, 38.4, 39.3, 42.3, 44.6, 46.3, 85.0, 109.8, 112.6, 112.8, 125.0,
131.1, 141.0, 161.3, 164.2, 192.9.
MS (APCI): m/z (%) = 376.9 [100, (M + Na)+].
HRMS (ESI): m/z (M – H)– calcd for C23H29O3–: 353.2111; found:
353.2116.
(±)-Rhododaurichomanic Acid A
To a solution of the aldehyde 32 (20.0 mg, 0.050 mmol) in t-BuOH (0.5
mL), MeCN (0.5 mL), 2-methylbut-2-ene (0.30 mL), and 1,2-dimeth-
oxyethane (0.20 mL) were added NaH2PO4 (28.0 mg, 0.25 mmol) and
NaClO2 (22.0 mg, 0.25 mmol, dissolved in 0.2 mL H2O) at –20 °C. After
stirring for an additional 2 h at –20 °C, the mixture was warmed up
slowly to r.t. and stirred overnight. Sat. aq NaCl (2 mL) was added and
(4) For applications in total syntheses, see: (a) Song, L.; Yao, H.;
Zhu, L.; Tong, R. Org. Lett. 2013, 15, 6. (b) Buchanan, G. S.; Cole,
K. P.; Tang, Y.; Hsung, R. P. J. Org. Chem. 2011, 76, 7027.
(c) Buchanan, G. S.; Cole, K. P.; Li, G.; Tang, Y.; You, L.; Hsung, R.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2713–2720

2720
G.-Y. Luo et al.
Special Topic
Synthesis
P. Tetrahedron 2011, 67, 10105. (d) Yamashita, S.; Iso, K.;
Kitajima, K.; Himura, M.; Hirama, M. J. Org. Chem. 2011, 76,
2408.
(21) Murrayamine, M.; Wu, T.-S.; Wang, M.-L.; Wu, P.-L.; Ito, C.;
Furukawa, H. Phytochemistry 1996, 41, 1433.
(22) (a) Kurdyumov, A. V.; Lin, N.; Hsung, R. P.; Gullickson, G. C.;
Cole, K. P.; Sydorenko, N.; Swidorski, J. J. Org. Lett. 2006, 8, 191.
(b) Sagar, R.; Singh, P.; Kumar, R.; Maulik, P. R.; Shaw, A. K. Car-
bohydr. Res. 2005, 340, 1287. (c) Lee, Y. R.; Kim, D. H.; Shim, J.-J.;
Kim, S. K.; Park, J. H.; Cha, J. S.; Lee, C.-S. Bull. Korean Chem. Soc.
2002, 23, 998.
(23) Zehnder, L. R.; Dahl, J. W.; Hsung, R. P. Tetrahedron Lett. 2000,
41, 1901.
(24) Melliou, E.; Magiatis, P.; Mitaku, S.; Skaltsounis, A.-L.; Chinou,
E.; Chinou, I. J. Nat. Prod. 2005, 68, 78.
(25) For isolation of eriobrucinol, see: (a) Jefferies, P. R.; Worth, G. K.
Tetrahedron 1973, 29, 903. (b) Bukuru, J.; Van, T. N.; Puyvelde, L.
V.; He, W.; De Kimpe, N. Tetrahedron 2003, 59, 5905. (c) For
additional data on eriobrucinol, see: Rashid, M. A.; Armstrong, J.
A.; Gray, A. I.; Waterman, P. G. Phytochemistry 1992, 31, 3583.
(26) For total syntheses of iso-eriobrucinol A and B, and eriobruci-
nol, see: (a) Crombie, L.; Redshaw, S. D.; Black, D. A.; Whiting, D.
A. J. Chem. Soc., Chem. Commun. 1979, 628. (b) Crombie, L.;
Redshaw, S. D.; Black, D. A.; Whiting, D. A. J. Chem. Soc., Perkin
Trans. 1 1983, 1411.
(27) (a) Gassman, P. G.; Chavan, S. P.; Fertel, L. B. Tetrahedron Lett.
1990, 31, 6489. (b) Gassman, P. G.; Lottes, A. C. Tetrahedron Lett.
1992, 33, 157.
(28) (a) Ko, C.; Feltenberger, J. B.; Ghosh, S. K.; Hsung, R. P. Org. Lett.
2008, 10, 1971. (b) Feltenberger, J. B.; Ko, C.; Deng, J.; Ghosh, S.
K.; Hsung, R. P. Heterocycles 2012, 84, 843. (c) Deng, J.; Hsung, R.
P.; Ko, C. Org. Lett. 2012, 14, 5562.
(5) For a leading review, see: Tang, Y.; Oppenheimer, J.; Song, Z.;
You, L.; Zhang, X.; Hsung, R. P. Tetrahedron 2006, 62, 10785.
(6) For leading reviews, see: (a) Tietze, L. F. Chem. Rev. 1996, 96,
115. (b) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993,
32, 131. (c) Tietze, L. F. J. Heterocycl. Chem. 1990, 27, 47.
(7) For a recent review on biomimetic synthesis, see: Bulger, P. G.;
Bagal, S. K.; Marquez, R. Nat. Prod. Rep. 2008, 25, 254.
(8) See also: (a) Yoder, R. A.; Johnston, J. N. Chem. Rev. 2005, 105,
4730. (b) Beaudry, C. M.; Malerich, J. P.; Trauner, D. Chem. Rev.
2005, 105, 4757. (c) Pindur, U.; Schneider, G. H. Chem. Soc. Rev.
1994, 23, 409.
(9) Shen, H. C.; Wang, J.; Cole, K. P.; McLaughlin, M. J.; Morgan, C.
D.; Douglas, C. J.; Hsung, R. P.; Coverdale, H. A.; Gerasyuto, A. I.;
Hahn, J. M.; Liu, J.; Wei, L.-L.; Sklenicka, H. M.; Zehnder, L. R.;
Zificsak, C. A. J. Org. Chem. 2003, 68, 1729.
(10) For some earlier studies, see: (a) Stevenson, R.; Weber, J. V.
J. Nat. Prod. 1988, 51, 1215. (b) Schuda, P. F.; Price, W. A. J. Org.
Chem. 1987, 52, 1972. (c) de March, P.; Moreno-Mañas, M.;
Casado, J.; Pleixats, R.; Roca, J. L. J. Heterocycl. Chem. 1984, 21,
85. (d) Tietze, L. F.; Kiedrowski, G. V.; Berger, B. Synthesis 1982,
683.
(11) For a leading review, see: Shen, H. C. Tetrahedron 2009, 65, 3931.
(12) Kang, Y.; Mei, Y.; Du, Y.; Jin, Z. Org. Lett. 2003, 5, 4481.
(13) (a) Wang, X.; Lee, Y. R. Tetrahedron 2011, 67, 9179; and refer-
ences cited therein. (b) Jung, E. J.; Park, B. H.; Lee, Y. R. Green
Chem. 2010, 12, 2003. (c) Wang, X.; Lee, Y. R. Tetrahedron 2009,
65, 10125.
(14) (a) Mondal, M.; Puranik, V. G.; Argade, N. P. J. Org. Chem. 2007,
72, 2068. (b) See also: Zeng, H.; Duan, D.; Tang, B. Synlett 2015,
26, 927.
(29) Jpn. Kokai Tokyo Koho JP 82-28080, 1982; Chem. Abstr. 1982, 97,
3777.
(30) For isolation, see: Kashiwada, Y.; Yamazaki, K.; Ikeshiro, Y.;
Yamagishi, T.; Fujioka, T.; Mihashi, K.; Mizuki, K.; Cosentino, L.
M.; Fowke, K.; Morris-Natschke, S. L.; Lee, K.-H. Tetrahedron
2001, 57, 1559.
(15) Yeom, H.-S.; Li, H.; Tang, Y.; Hsung, R. P. Org. Lett. 2013, 15,
3130.
(16) Hua, D. H.; Chen, Y.; Sin, H.-S.; Maroto, M. J.; Robinson, P. D.;
Newell, S. W.; Perchellet, E. M.; Ladesich, J. B.; Freeman, J. A.;
Perchellet, J.-P.; Chiang, P. K. J. Org. Chem. 1997, 62, 6888.
(17) (a) Wei, L.-L.; Hsung, R. P.; Sklenicka, H. M.; Gerasyuto, A. I.
Angew. Chem. Int. Ed. 2001, 40, 1516. (b) Sklenicka, H. M.;
Hsung, R. P.; McLaughlin, M. J.; Wei, L.-L.; Gerasyuto, A. I.;
Brennessel, W. W. J. Am. Chem. Soc. 2002, 124, 10435.
(18) (a) Gerasyuto, A. I.; Hsung, R. P.; Sydorenko, N.; Slafer, B. W.
J. Org. Chem. 2005, 70, 4248. (b) Cravotto, G.; Nano, G. M.;
Tagliapietra, S. Synthesis 2001, 49.
(31) For total syntheses, see: (a) Kurdyumov, A. V.; Hsung, R. P.;
Ihlen, K.; Wang, J. Org. Lett. 2003, 5, 3935. (b) Hu, H.; Harrison,
T. J.; Wilson, P. D. J. Org. Chem. 2004, 69, 3782. (c) See also: Ref.
12.
(32) Kurdyumov, A. V.; Hsung, R. P. J. Am. Chem. Soc. 2006, 128, 6272.
(33) (a) Roll, D. M.; Manning, J. K.; Carter, G. T. J. Antibiot. 1998, 51,
635. (b) For fermentation studies, see: Abbanat, D. A.; Singh, M.
P.; Greenstein, M. J. Antibiot. 1998, 51, 708.
(34) For an earlier total synthesis of hongoquercin A, see:
(a) Tsujimori, H.; Bando, M.; Mori, K. Eur. J. Org. Chem. 2000,
297. (b) Tsujimori, H.; Mori, K. Biosci. Biotechnol. Biochem. 2000,
64, 1410.
(19) Hsung, R. P.; Shen, H. C.; Douglas, C. J.; Morgan, C. D.; Degen, S.
J.; Yao, L. J. J. Org. Chem. 1999, 64, 690.
(20) (a) For a related condensation using ethylenediamine acetate
salt that led to cannabichromeme, see: Lee, Y. R.; Wang, X. Bull.
Korean Chem. Soc. 2005, 26, 1933. (b) See also: Mechoulam, R.;
Yapnitinsky, B.; Gaoni, Y. J. Am. Chem. Soc. 1968, 90, 2420.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2713–2720