Total Synthesis of (+)-Lycoricidine and Conduramine B-1, ent-C-1, C-4, D-1, ent-F-1, and ent-F-4, and Formal Synthesis of (-)-Laminitol: A C2-Symmetric Chiral-Pool-Based Flexible Strategy

Article abstract of DOI:10.1021/acs.joc.9b01221

A facile and diversity-oriented synthetic strategy toward aminocyclitol natural products from inexpensive C₂-symmetric l-tartaric acid was developed. The pivotal epoxide was used as a common intermediate to accomplish eight diverse target molec

Full text of DOI:10.1021/acs.joc.9b01221

Subscriber access provided by Nottingham Trent University
Article
Total Synthesis of (+)-Lycoricidine, Conduramine B-1, ent-
C-1, C-4, D-1, ent-F-1, ent-F-4, and Formal Synthesis of (#)-
Laminitol — a C2-Symmetric Chiral Pool-Based Flexible Strategy
Hong-Jay Lo, Yuan-Kang Chang, Bakthavachalam
Ananthan, Yu-Hsuan Lih, Kuang#Shun Liu, and Tu-Hsin Yan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01221 • Publication Date (Web): 23 Jul 2019
Downloaded from pubs.acs.org on July 23, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 14
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Total Synthesis of (+)-Lycoricidine, Conduramine B-1, ent-C-1, C-4,
D-1, ent-F-1, ent-F-4, and Formal Synthesis of (‒)-Laminitol — a C2-
Symmetric Chiral Pool-Based Flexible Strategy
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Hong-Jay Lo,† Yuan-Kang Chang,† Bakthavachalam Ananthan, Yu-Hsuan Lih, Kuang-Shun Liu, Tu-Hsin Yan*
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan.
†These authors contributed equally.
KEYWORDS: Lycoricidine, Conduramine, Laminitol, Chiral Pool, Tartaric acid.
ABSTRACT: Facile and diversity oriented synthetic strategy towards aminocyclitol natural products from inexpensive C2-
symmetric L-tartaric acid was developed. Pivotal epoxide was used as a common intermediate to accomplish eight diverse
target molecules in six to eleven steps. Various allyl amine type conduramines were synthesized in a diastereoselective
manner. Heck arylation was explored to construct phenanthridone ring in a concise synthesis of (+)-lycoricidine. In
addition, a highly efficient formal synthesis of (−)-laminitol was developed.
INTRODUCTION
The Amaryllidaceae alkaloids family,1 such as lycoricidine
(1 Figure 1) and narciclasine (2) gained attention for their
biological properties ranging from antitumor to antiviral,
antibacterial, antifungal, antimalarial and analgesic
activities.2 However, the precise mechanisms of their
action have not been fully elucidated. First isolated from
the bulbs of Lycoris radiate,3 lycoricidine has multiple
chiral centers stimulating interest in the synthesis of this
natural product difficult to obtain in multi-gram scale from
natural sources. Since the first total synthesis by Ohta in
1976,4 around 20 papers have been published disclosing the
synthetic approaches to lycoricidine 1.5 Among the recent
examples, an expedite 6-step synthesis of lycoricidine
reported by Sarlah provided a final product in 26 % yield.5g
At the same time, other aminocyclohexenetriols (e.g.,
conduramines, a family of diastereomerically diverse allyl
amine small molecule analogs of conduritol) have
continued to attract synthetic interest due to their
stereoisomeric architectures and unique biological
activities (Figure 1).6 Several synthetic approaches toward
construction of the requisite stereoisomeric skeleton for
the synthesis of conduramines A-1,7 B-1,6b,8 D-1,7c,9 E-1,7a,f,10
C-1,7a,b,9,11 C-4,7c,12 F-1,6c,7b,c,f,10,13 and F-414 have been reported.
Conduramines also serve as chiral pools for the synthesis
of various natural products, such as (+)-valienamine,7a (+)-
lycoricidine and (+)-narciclasine15 that possess potent
glucosidase inhibitory6 and a broad spectrum of anticancer
activities respectively. Although many creative approaches
toward the lycoricidine and
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 14
Figure 1. Structure of some conduramines and aminocyclitol-
type natural products.
1
2
3
4
Scheme 1 Retrosynthesis of Conduramine B-1, ent-C-1, C-4, D-1, ent-F-1 and ent-F-4, Key Intermediate of (–)-
Laminitol, and (+)-Lycoricidine.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
conduramine scaffolds have been developed, the majority
of strategies gave the product in low yields. Thus, from a
practical viewpoint, the high-yielding protocols for the
chemical synthesis of lycoricidine and conduramines are
highly desired. Not only the total synthesis of these natural
products has gained attention, but their precursors also
amine 12, which could be derived from L-(+)-tartaric acid
14 through allylic epoxide 10. The compound 10 could be
obtained from diol 13 through activation of one hydroxyl
group as an electrophile and intramolecular displacement
by another hydroxyl nucleophile. Finally, conduramines 3-
8 were ex-
became valuable targets.
Thus, we envisioned
Scheme 2 Total Synthesis of (+)-Lycoricidine 1.
stereochemical diversity synthesis of conduramines and
lycoricidine. Importantly, an efficient synthesis of libraries
based on these natural products would facilitate basic SAR
studies to identify the core pharmacophore and furnish
potent and selective analogs, which are difficult to obtain
through the direct modification of natural products.
Recently, we reported an efficient synthetic strategy for
various natural products including (–)-hygromycin A,16
conduramines A-17a and E-1,7a,h and (+)-valienamine,7a a key
intermediate of (+)-pancratistatin, from the common
chiral substrates. Herein, we present a C2-symmetric
chiral pool-based approach.
diastereoselective protocol
This expeditious and
delivers synthetically
challenging (+)-lycoricidine (1), and stereomerically
diverse conduramines (3-8) through an allylic epoxide 10,
which is prepared from inexpensive L-(+)-tartaric acid. In
a complementary note, we also report a formal synthesis of
(−)-laminitol 9.17 (Figure 1).
RESULTS AND DISCUSSION
We designed a concise convergent strategy to access (+)-
lycoricidine and various conduramines from the same
readily available intermediate. Scheme 1 outlines our
overall retrosynthesis. In lycoricidine synthesis, we
planned to explore Heck arylation and amidation for the
construction of the required phenanthiridine 11 from allyl
ACS Paragon Plus Environment

Page 3 of 14
The Journal of Organic Chemistry
Reagents and conditions: (a) ref. 7a, 16, 39% (4 steps from
We also examined the effect of bases, including TEA,
Tl(OAc), Cs2CO3 and K2CO3 (Table 1). Similar to Ogawa’s5e
results, the optimized Heck conditions with
Pd(OAc)2/PPh3 using thallium(I) salt as a base furnished
tetracyclic phenanthirdine ring (11) with the highest yield
(78%). Final deprotection consisted of removal of tert-
butyloxycarbonyl and acetonide by the treatment of 11 with
catalytic Mg(ClO4)222 in acetonitrile, and TBS removal with
TBAF in THF at room temperature to afford (+)-
lycoricidine 1. Physical properties of (+)-lycoricidine 1 were
found to be in accordance with the literature reports.5 The
developed C2-symmetric chiral pool-based strategy, which
entailed only 11 steps from the very cheap L-tartaric acid 14,
provided (+)-lycoricidine in 10% overall yield.
14) (b) NaH, TBSCl, THF, r.t., 6 h, 82%. (c) LAH, ether, 0 oC, 1
h, 93% (d) 17, DCC, DMAP, THF, r.t. 12 h, 90%. (e) Boc2O,
DMAP, CH3CN, 90 oC, 3 h, 89%. (f) Pd(OAc)2, PPh3, Tl(OAc),
1
2
3
4
5
6
7
8
o
o
CH3CN, 90 C, 36 h, 78%. (g) Mg(ClO4)2, CH3CN, 90 C, 5 h,
67%. (h) TBAF, THF, r.t., 3 h, 79%. Abbreviations: TBAF =
tetra-n-butylammonium fluoride.
Table 1 Optimization of the phenanthiridine 11
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Synthesis of Conduramine C-4 and ent-
Conduramine F-1.
Pd(OAc)2
(mol%)
PPh3
Yield
(%)a
Entry
Base
(equiv.)
1
3
Et3N
0.12
40b
78
2
3
4
20
20
20
Tl(OAc)
Cs2CO3
K2CO3
1
1
1
55
60c
a Isolated Yield. b Dehalogened product was observed. C Side
product 12 was observed.
pected to arise via SN2 and SN2’ reactions at allylic epoxide
10 with nitrogen, halogen and oxygen nucleophiles.
Synthesis of (+)-lycoricidine
1
commenced with
preparation of cyclic diol 13 from the commercially
available and inexpensive L-tartaric acid 14 (Scheme 2) by
following the procedures reported by our group7a,h,16,18 and
others.19 Cyclic diol 13 was subjected to a base-promoted
monotriflation of the hydroxyl group, followed by
intramolecular displacement by another hydroxyl
nucleophile to furnish pivotal epoxide 10. A nucleophilic
ring opening of the allylic epoxide 10 at the allylic carbon
with an azide ion gave 1,2-type azido alcohol 15 with the
inversion of configuration. Previously, we demonstrated
an efficient strategy to access both 1,2- and 1,4-type azido
alcohols.7a In order to obtain a suitable substrate for Heck
arylation, secondary alcohol 15 was protected with TBS and
subsequently the azido group was reduced by LAH to give
allyl amine 12 in 93% yield. Amidation of 12 with 6-
iodopiperonylic acid 1720 in the presence of DCC and
DMAP afforded the desired amide 18 in excellent yield.
Reagents and conditions: (a) 5 mol% TFA, CH2Cl2, 10 oC, 4
o
h; then DMP, 30 min., 77%. (b) DIBAL-H, CH2Cl2, –78 C, 30
min., S-isomer 8%, R-isomer 68% (S:R = 1:8.5). (c) LAH, ether,
o
0 C, 1 h; then 80% AcOH, 110 or 50 oC, 22 h; then Ac2O,
pyridine, r.t., 16 h, 23: 58%, 26: 89%. (d) ref. 7a, 70%. (e) PPh3,
DEAD, BzOH, THF, 2 h, 87%. Abbreviations: DEAD = diethyl
azodicarboxylate. DMP = Dess-Martin periodinane. TFA =
trifluoroacetic acid. DIBAL-H = diisobutylaluminum hydride.
LAH = lithium aluminium hydride.
Following the steps from Scheme 2, the synthesis of 1,2-
anti-type azido alcohol 15 was achieved in four steps from
L-tartaric acid 1.7a,16 The subsequent conversion of the
trans-acetonide to a more stable cis-acetonide was
performed by treating the azido alcohol 15 with TFA (0.02
equiv.) (Scheme 3). Oxidation of the allylic alcohol with
Dess-Martin periodinane gave enone 21 in high yield.
Although reduction of α,β-unsaturated ketones have been
reported, conditions for the reduction of enone 21 had to
be optimized with regard to selectivity and yield. Several
reagents, such as NaBH4/CeCl3·7H2O, LiBH4/CeCl3·7H2O,
NaBH4, Zn(BH4)2, LiAlH(OtBu)3, LiAlH(OtBu)3/LiI, and L-
selectride, were found to be ineffective to reduce enone 21.
Fortunately, we found that treatment of enone 21 with
The next objective was the formation of the final
phenanthiridine ring via an intramolecular Heck reaction.
First, we tested Heck arylation on secondary amide 18 that
only gave a dehalogenated compound along with starting
material. According to the literature reports,5b,21 tertiary
amides are more suitable for the intramolecular Heck
arylation. Therefore, we prepared tertiary amide (19) by
treating 18 with Boc2O and DMAP at 90 °C. After screening
the reaction conditions for Heck cyclization, we identified
Pd(OAc)2 in CH3CN to give product in acceptable yields.
o
DIBAL-H at –78 C furnished 22 in good yield with good
selectivity (68%, α:β = 1: 8.5).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 14
The remaining steps to the final product consisted of azide single isomer with good yield. Further treatment of 31
1
2
3
4
5
6
7
8
reduction, acetonide deprotection, and acylation of
hydroxyl and amino groups. To improve overall yield, we
aimed to accomplish the transformations in one pot. Thus,
treatment of 22 with LiAlH4 subsequent acetonide
deprotection and preacylation in one pot provided the
desired tetraacetyl conduramine C-4 23 (Scheme 3).
conduramine D-1 32.
in the presence of 2 mol% Pd(PPh3)4, the 1,4-syn allylic
alcohol 33 was obtained (Scheme 5a). Similarly, the
palladium-catalyzed nucleophilic opening of allyl epoxide
10 with TsNH2/TsNHNa25 in CH3CN at 40 °C gave 1,4-syn-
amide 34 along with small amount of diene 34a. The high
stereoselectivity of 1,4-syn-addition could be explained by
the
Scheme 4. Synthesis of Conduramine C-1 and
Conduramine D-1.
9
Schemes 5a and 5b Synthesis of Conduramine B-1, ent-
Conduramine F-4, Formal Synthesis of Laminitol and
plausible mechanism for soft nucleophile induction.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Reagents and conditions: (a) ref. 7h, 16, 87%. (b) NaN3,
NH4Cl, DMF, r.t., 12h, 91%. (c) LAH, ether, 0 oC, 1 h; then 80%
AcOH, 50 or 110oC, 22 h; then Ac2O, pyridine, r.t., 16 h, 29: 68%
or 32: 62%. (d) 4 mol% TFA, CH2Cl2, 10 oC, 2 h; then DMP, 30
min., 66%. (e) NaBH4, CeCl3·7H2O, MeOH, –78 oC, 1 h, 91%.
The 1,4-anti-type azido alcohol 24 was synthesized from
cyclic diol 13 through [3,3] sigmatropic rearrangement.7a In
order to attain the desired configuration, the allylic
hydroxyl group of 24 was subjected to Mitsunobu
inversion.23 Thus, treatment of 24 with DEAD, BzOH, and
PPh3 in THF for 2 hours provided 1,4-syn-type azido alcohol
derivative 25 in 89% yield. Reduction of 25 with LiAlH4,
followed by the one-pot acetonide deprotection and
peracylation afforded the tetraacetyl ent-conduramine F-1
26 (Scheme 3).
o
Reagents and conditions: (a) Pd(PPh3)4, BzOH, THF, 0 C,
30 min., 95%. (b) TsNH2, TsNHNa, Pd(PPh3)4, THF, 0 oC to r.t.,
30 h, 34: 69%, 34a: 8% (ca. 8.5:1 dr). (c) MsCl, Et3N, DMF, 0 oC,
o
20 min.; then NaN3, 2 h, 88%. (d) LAH, ether, 0 C, 1 h; then
80% AcOH, 50 oC, 22 h; then Ac2O, pyridine, r.t., 16 h, 67%. (e)
6 mol% TFA, CH2Cl2, 50 oC, 30 h; then DMP, r.t., 15 h, 71%. (f)
In order to obtain 1,2-cis-type azido alcohol 28, we decided
to perform a double SN2 on the allylic epoxide 10. The
bromo-hydrin 27 was prepared from allylic epoxide 10 in a
regioselective manner.7h,16 The bromohydrin 27 was
subjected to nucleophilic substitution with azide to give
azido alcohol 28. Treatment of 28 with LiAlH4, followed by
the one-pot acetonide deprotection and peracylation
afforded the tetraacetyl ent-conduramine C-1 29 (Scheme
4).
o
CH2N2, MeOH, r.t., 20 min., 70%. (g) LAH, ether, 0 C, 1 h;
then 80% AcOH, 110oC, 22 h, 91%. (h) ref 17a, 26% (2 steps). (i)
o
o
Na, NH3, –78 C, 45 min.; then 80% AcOH, 50 C, 18 h; then
Ac2O, pyridine, cat. DMAP, r.t., 18 h, 82%.
Toward product 32, the TFA-catalyzed rearrangement of 28
gave thermally stable cis-fused acetonide, which led to
enone 30 after oxidation with Dess-Martin periodinane.
Unlike the conversion of 21 to 22, the Luche reduction of
enone 30 yielded 1,4-cis-type azido alcohol 31.24 Luche
reduction from the convex face of the ketone gave only a
ACS Paragon Plus Environment

Page 5 of 14
The Journal of Organic Chemistry
mediated allylic substitution reaction of soft nucleophile
1
2
3
4
5
6
with palladium π-allyl system provided 1,4-syn-alcohol
intermediate, which was used to accomplish the formal
synthesis of (–)-lamintol. The versatile protocol presented
above should streamline generation of aminocyclitol-
containing natural products and derivatives for the
investigation of their biological activities.
7
8
EXPERIMENTAL SECTION
All reactions were carried out under an inert atmosphere
of N2 unless mentioned otherwise, and standard syringe–
septa techniques were followed. Solvents were purchased
from commercial solvent and used without further
purification. The progress of all the reactions were
monitored by TLC, using TLC glass plates precoated with
silica gel 60 F254 (Merck). The TLC was detected by UV
light (254 nm), or phosphomolybdic acid. Column
chromatography was performed on Merck silica gel 60
(230-400 mesh). 1H and 13C{1H} NMR spectra were recorded
9
10
11
12
13
14
15
steric bulk of the palladium(II) complex, which shields the
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
α face of the palladium π-allyl system from the attack by
soft nucleophile (Scheme 5b).26
o
with a Varian VXR-400 MHz spectrometer at 25 C and
The remaining steps towards tetraacetyl conduramine
B-1, tetraacetyl ent-conduramine F-4 and laminitol 9 are
presented in Scheme 5a. The allylic alcohol unit in 33 was
converted to allylic azide through mesylation, followed by
nucleophilic displacement with sodium azide to give allylic
azide 35. Reduction of 35 with LiAlH4, followed by the one-
pot acetonide deprotection and peracylation afforded the
tetraacetyl conduramine B-1 36 (Scheme 5).
chemical shifts were measured in δ (ppm) with residual
solvent peaks as internal standards (CDCl3, δ 7.24 ppm and
1
CD3OD, δ 3.30 ppm, in H NMR and CDCl3, δ 77 ppm,
CD3OD, δ 49 ppm, in 13C{1H} NMR). Coupling constants (J),
measured in Hz. Data are represented as follows:chemical
shift, multiplicity (s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, br = broad). High-resolution mass
spectra were determined on
a
Jeol JMS-HX 110
spectrometer. Optical rotations were obtained on an
Optical Activity AA-100 polarimeter.
As in the prior cases, the trans-acetonide 33 was converted
to cis-acetonide, which was then subjected to oxidation
affording 37. Diazomethane-mediated transformation of
ketone 37 into exo-epoxide 38 was accomplished in high
yield.27 In order to obtain the tetraol 39, which is a key
intermediate en route to (–)-laminitol 9,17a the exo-epoxide
38 was subjected to LiAlH4-promoted reduction and
HOAc-promoted deprotection steps. Starting from L-
tartaric acid, the formal synthesis of (–)-laminitol was
accomplished in 10 steps with 8.7% overall yield (Scheme
5a). Starting from the pivotal epoxide 10, the tosylamide
34 was prepared in a regioselective manner via the double
SN2 on the allylic epoxide. After careful optimization of the
reaction conditions, the treatment of the tosylamide 34
with Na/NH3, followed by acetonide hydrolysis and
peracetylation resulted in the efficient formation of
tetraacetyl ent-conduramine F-4 40 in 82% yield (Scheme
5a).
(((3aR,4S,5R,7aS)-5-azido-2,2-dimethyl-3a,4,5,7a-
tetrahydrobenzo[d][1,3]dioxol-4-yl)oxy)(tert-
butyl)dimethylsilane (16). To a suspension of NaH (60%,
132 mg, 3.30 mmol, 4.2 equiv.) in anhydrous THF (5 mL)
was added azido alcohol 157a (167 mg, 0.79 mmol, 1.0 equiv.)
dissolved in anhydrous THF (5 mL) at room temperature
under nitrogen atmosphere and allowed to stir for 10 min.,
followed by TBSCl (tert-butylchlorodimethylsilane) (241
mg, 1.58 mmol, 2.0 equiv.) in anhydrous THF (5 mL) was
added dropwise and stirred for 6 h at room temperature
until TLC indicated disappearance of starting material
(EtOAc : hexane = 1 : 3, Rf startng metarial : alcohol = 0.4 :
0.9). Upon completion, it was carefully quenched with
water at 0 oC and diluted with EtOAc (15 mL) and washed
with water (10 mL) and then brine. The aqueous layer was
extracted with EtOAc (2×10 mL) and the combined organic
phases were dried over MgSO4, concentrated in vacuo. The
resulting residue was purified by silica gel column
chromatography using EtOAc : hexane (1 : 10) as eluents to
give silyl ether 16 as white soild ( 213 mg, 82%). Rf = 0.90
CONCLUSION
In summary, we developed several synthetic routes for the
synthesis of various aminocyclitol-type natural products
starting from the pivotal allylic epoxide. Our protocols
provided an easy access to 1,2-syn-, 1,2-anti-, 1,4-syn-, and
25
(silica gel, EtOAc ： hexane = 1 ： 3); [α]D = -121o (c 2.1,
CH2Cl2); IR (film) νmax 2932, 2097, 1698, 1649, 1383, 836 cm-
1; 1H NMR (400 MHz, CDCl3): δ 6.33 (dd, J=10.4, 0.8 Hz, 1H),
5.58 (ddd, J=10.4, 3.2, 0.8 Hz, 1H), 4.49-4.46 (m, 1H), 4.24
(br, 1H), 3.87-3.86 (m, 1H), 3.50 (dd, J=8.4, 2.0 Hz, 1H), 1.44
(s, 3H), 1.41 (s, 3H), 0.87 (s, 9H), 0.09 (s, 6H); 13C{1H} NMR
(100 MHz, CDCl3): δ 131.0, 123.0, 111.4, 78.6, 71.2, 70.3, 64.6,
26.9, 26.5, 25.7, 18.1, -4.6, -5.1; HRMS (FAB, magnetic
sector) m/z: [M+H]+ calcd for C15H28N3O3Si 326.1900; found
326.1901.
1,4-anti-amino precursors in high yields.
The C2-
symmetric chiral pool approach through 1,2-anti-amino
intermediate was shown to be highly valuable for the total
synthesis of (+)-lycoricidine, which was obtained in 11 steps
in 10% overall yield. In addition, we accomplished an
expeditious synthesis toward conduramines, including B-1,
ent–C-1, C-4, D-1, ent–F-1, ent–F-4, from single
intermediate, allyl epoxide 10.
The palladium(II)-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 14
(3aR,4S,5R,7aS)-4-((tert-butyldimethylsilyl)oxy)-2,2- equiv.) and (Boc)2O (di-tert-butyldicarbonate) (0.08 mL,
0.34 mmol, 2.0 equiv.) and stirred at 90 oC for 3 h until TLC
indicated disappearance of starting material (EtOAc :
hexane = 1 : 5, Rf startng metarial : product = 0.2 : 0.5). Upon
completion, it was diluted with EtOAc (20 mL) and washed
with satd aq. NaHCO3 (8 mL) and then brine. The
combined organic layers were dried over MgSO4, filtered
and concentrated in vacuo. The resulting residue was
purified by silica gel column chromatography using EtOAc
: hexane (1 : 10) as eluents to give compound 19 as white
soild (104 mg, 89%). Rf = 0.50 (silica gel, EtOAc : hexane =
1 : 5); [α]D25 = -23.8o (c 2.1, CHCl3); IR (film) νmax 3420, 2931,
1
2
3
4
5
6
7
8
dimethyl-3a,4,5,7a-tetrahydrobenzo[d][1,3] dioxol-5-
amine (12). A solution of azido 16 (126 mg, 0.39 mmol, 1
equiv.) in anhydrous ether (5 mL) was dropwisely added to
a 0 oC suspension consisting of LiAlH4 (29 mg, 0.77 mmol,
2.0 equiv.) in anhydrous ether (5 mL). After stirring 1 hour
o
at 0 C, a small amount of water is carefully added to
destroy the excess LiAlH4 at 0 oC and diluted with ether (10
mL). The solution was filtered through a pad of Celite,
washed with ether (3×5 mL), dried over MgSO4,
concentrated in vacuo. The resulting residue without
purified and gave pure product amine 12 as white soild (108
mg, 93%). Rf = 0.50 (silica gel, EtOAc); [α]D25 = +15.5o (c 1.1,
CHCl3); IR (film) νmax 3383, 3330, 1617, 1380, 1230, 1067, 837
cm-1; 1H NMR (400 MHz, CDCl3): δ 6.05 (ddd, J=10.1, 1.5, 1.1
Hz, 1H), 5.55-5.51 (m, 1H), 4.49-4.46 (m, 1H), 4.06 (br, 1H),
3.59 (dd, J=8.6, 1.8 Hz, 1H), 3.43-3.41 (m, 1H), 1.44 (s, 3H),
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2857, 1737, 1675, 1477, 1234, 1146, 872 cm-1; H NMR (400
MHz, CDCl3): δ 7.19 (s, 1H), 6.69 (br, 1H), 6.21 (ddd, J=4.4,
3.2, 1.6 Hz, 1H), 5.98 (s, 2H), 5.51 (d, J=9.6 Hz, 1H), 5.24 (dd,
J=4.8, 2.4 Hz, 1H), 4.44 (ddd, J=6.4, 4.0, 2.4 Hz, 1H), 4.38 (d,
J=3.2 Hz, 1H), 4.15 (dd, J=8.8, 3.6 Hz, 1H), 1.46 (s, 3H), 1.44
(s, 3H), 1.23 (s, 9H), 0.90 (s, 9H), 0.11 (s, 3H), 0.10 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 170.2, 151.9, 149.1, 148.2,
137.3, 127.6, 126.7, 118.8, 111.9, 107.9, 102.1, 84.3, 80.7, 79.2,
71.2, 69.8, 63.0, 27.6, 27.4, 26.9, 25.8, 18.2, -4.3, -4.9; HRMS
(FAB, magnetic sector) m/z: [M]+ calcd for C28H40INO8Si
673.1568; found 673.1575.
13
1.42 (s, 3H), 0.88 (s, 9H), 0.09 (s, 6H); C{1H} NMR (100
MHz, CDCl3): δ 130.0, 126.4, 110.9, 78.9, 73.5, 71.8, 57.8, 27.1,
26.6, 25.7, 18.2, -4.6, -4.9; HRMS (FAB, magnetic sector)
m/z: [M+H]+ calcd for C15H30NO3Si 300.1995; found
300.1997.
N-((3aR,4S,5R,7aS)-4-((tert-butyldimethylsilyl)oxy)-
2,2-dimethyl-3a,4,5,7a-tetrahydrobenzo[d][1,3]dioxol-
5-yl)-6-iodobenzo[d][1,3]dioxole-5-carboxamide (18).
tert-butyl
(3aR,4S,4aR,12aS)-4-((tert-butyldimethyl
silyl)oxy)-2,2-dimethyl-6-oxo-4,4a,6,12a-tetrahydrobis
To
a
stirred
solution
of
DCC
(N,N´-
([1,3]dioxolo)[4,5-b:4',5'-j]phenanthridine-5(3aH)-
dicyclohexylcarbodiimide) (344 mg, 1.67 mmol, 2.0 equiv.)
in anhydrous THF (10 mL) was added at 0 oC 6-
iodopiperonylic acid 1720 (239 mg, 1.00 mmol, 1.2 equiv.)
and DMAP ((4-dimethylamino)pyridine) (204 mg, 1.67
mmol, 2.0 equiv.) stirred for an additional 30 minutes at 0
oC. The reaction mixture was added a solution of amine 12
(250 mg, 0.83 mmol, 1.0 equiv.) in anhydrous THF (5 mL)
at 0 oC and then allowed to stir to room temperature for 12
hours until TLC indicated disappearance of starting
material (EtOAc, Rf startng metarial : product = 0.5 : 0.9).
Upon completion, it was diluted with EtOAc (20 mL) a was
filtered through a pad of Celite, concentrated. The
obtained residue was purified by silica gel column
chromatography using EtOAc : hexane (1 : 5) as eluents to
give carbamate 18 as white soild (413 mg, 90%). Rf = 0.20
carboxylate (11). To
a
stirred solution of PPh3
(triphenylphosphine) (20 mg, 0.077 mmol, 1.0 equiv.) in
anhydrous CH3CN (2 mL) was added Pd(OAc)2
(palladium(II) acetate) (3.5 mg, 0.016 mmol, 0.20 equiv.) at
room temperature and stirred for an additional 30 minutes.
The reaction mixture was added a solution of iodobenzene
19 (52 mg, 0.077 mmol, 1.0 equiv.) in anhydrous CH3CN (1
mL) and Tl(OAc) (thallium acetate) (41 mg, 0.16 mmol, 2.0
equiv.) and stirred at 90 oC for 36 hours until NMR
spectrum indicated disappearance of starting material.
Upon completion, it was diluted with EtOAc (10 mL) the
solution was filtered through a pad of Celite, washed with
EtOAc (3×5 mL) and concentrated in vacuo. The resulting
residue was purified by silica gel column chromatography
using EtOAc : hexane (1 : 10) as eluents to give compound
11 as white soild ( 33 mg, 78%). Rf = 0.50 (silica gel, EtOAc :
hexane = 1 : 5); [α]D25 = +132.5o (c 0.4, CH2Cl2); IR (film) νmax
2932, 1742, 1675, 1503, 1371, 1250, 1145, 836, 782 cm-1; 1H NMR
(400 MHz, CDCl3): δ 7.46 (s, 1H), 6.85 (s, 1H), 6.43 (br, 1H),
6.03 (d, J=5.6 Hz, 2H), 4.66 (d, J=5.6 Hz, 1H), 4.46 (s, 1H),
4.39 (d, J=0.8 Hz, 1H), 3.67 (dd, J=5.6, 1.2 Hz, 1H), 1.60 (s,
9H), 1.47 (s, 3H), 1.45 (s, 3H), 0.88 (s, 9H), 0.14 (s, 3H), 0.13
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 164.5, 154.4, 152.2,
148.5, 133.9, 130.0, 126.0, 120.8, 112.0, 107.6, 103.2, 101.9, 84.9,
79.8, 71.6, 67.1, 64.6, 27.7, 26.9, 26.7, 25.7, 17.9, -4.7, -4.9;
HRMS (FAB, magnetic sector) m/z: [M]+ calcd for
C28H39NO8Si 545.2445; found 545.2438.
(silica gel, EtOAc : hexane = 1 : 5); [α]D = -42.0o (c 2.5,
25
CHCl3); IR (film) νmax 3251, 2985, 1639, 1529, 1475, 838 cm-1;
1H NMR (400 MHz, CDCl3): δ 7.19 (s, 1H), 6.89 (s, 1H), 6.27
(ddd, J=10.0, 2.4, 1.2 Hz, 1H), 5.98 (s, 2H), 5.67 (d, J=8.4 Hz,
1H), 5.55 (dd, J=10.0, 4.0 Hz, 1H), 4.61-4.59 (m, 1H), 4.54 (d,
J= 8.4 Hz, 1H), 4.43 (s, 1H), 3.55 (dd, J=8.4, 2.4 Hz, 1H), 1.43
(s, 6H), 0.91 (s, 9H), 0.23 (s, 3H), 0.15 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 167.8, 149.7, 148.4, 135.1, 130.2, 125.2,
119.1, 111.2, 108.9, 102.1, 81.1, 79.6, 71.4, 69.7, 55.4, 27.0, 26.5,
25.8, 18.1, -4.8, -4.9; HRMS (FAB, magnetic sector) m/z:
[M+H]+ calcd for C23H33INO6Si 574.1122; found 574.1119.
tert-butyl
butyldimethylsilyl)
tetrahydrobenzo[d][1,3]
((3aR,4S,5R,7aS)-4-((tert-
oxy)-2,2-dimethyl-3a,4,5,7a-
dioxol-5-yl)(6-
(2S,3R,4S,4aR)-4-((tert-butyldimethylsilyl)oxy)-2,3-
dihydroxy-3,4,4a,5-tetrahydro-[1,3]dioxolo
[4,5-
iodobenzo[d][1,3]dioxole-5-carbonyl) carbamate (19).
To a stirred solution of carbamate 18 (100 mg, 0.17 mmol,
1.0 equiv.) in anhydrous CH3CN (10 mL) was added DMAP
((4-dimethylamino)pyridine) (43 mg, 0.35 mmol, 2.0
j]phenanthridin-6(2H)-one (20). To a stirred solution of
acetonide 11 (102 mg, 0.19 mmol, 1.0 equiv.) in anhydrous
CH3CN (2 mL) was added Mg(ClO4)2 (magnesium
perchlorate) (13 mg, 0.058 mmol, 0.30 equiv.) at room
ACS Paragon Plus Environment

Page 7 of 14
The Journal of Organic Chemistry
temperature. The reaction mixture stirred at 90 oC for 5 h
(EtOAc : hexane = 1 : 3, Rf allylic alcohol : product = 0.5 :
1
2
3
4
5
6
7
8
until TLC indicated disappearance of starting material
(EtOAc : hexane = 2 : 1, Rf startng metarial : product = 0.9 :
0.1). Upon completion, it was diluted with EtOAc (5 mL)
the solution was filtered through a pad of Celite, washed
with EtOAc (3×3 mL) and concentrated in vacuo. The
resulting residue was purified by silica gel column
chromatography using EtOAc : hexane (1 : 1) as eluents to
give diol 20 as white soild (51 mg, 67%). Rf = 0.13 (silica gel,
EtOAc : hexane = 2 : 1); [α]D25 = +58.5o (c 0.7, Acetone); IR
0.6). Upon completion, the solution was filtered through a
pad of Celite, concentrated. The obtained residue was
purified by silica gel column chromatography using EtOAc
: hexane (1 : 5) as eluents to give α,β-unsaturated ketone 21
as colorless oil (120 mg, 77%). Rf = 0.59 (silica gel, EtOAc :
hexane = 1 : 3); [α]D25 = -190o (c 3.1, CHCl3); IR (film) νmax
1
2110, 1693, 1380, 1223, 1160, 1078, 855 cm-1; H NMR (400
MHz, CDCl3): δ 6.76 (ddd, J=10.0, 4.0, 1.2 Hz, 1H), 6.24 (ddd,
J=10.0, 1.2, 0.4 Hz, 1H), 4.53 (ddd, J=5.6, 4.0, 1.2 Hz, 1H), 4.41
(d, J=5.6 Hz, 1H), 4.37-4.34 (m, 1H), 1.41 (s, 6H); 13C{1H}
NMR (100 MHz, CDCl3): δ 193.0, 142.6, 130.2, 110.7, 77.5,
74.2, 57.4, 27.3, 25.8; HRMS (EI, magnetic sector) m/z: [M]+
calcd for C9H11N3O3 209.0801; found 209.0802.
9
1
(film) νmax 3415, 3285, 1669, 1385, 1073, 775 cm-1; H NMR
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(400 MHz, CDCl3): δ 7.45 (br, 1H), 6.75 (br, 1H), 6.02 (dd,
J=4.4, 1.6 Hz, 2H), 5.97 (br, 1H), 5.73 (br, 1H), 4.39-4.36 (m,
1H), 4.32 (d, J=8.4 Hz, 1H), 4.06 (dd, J=8.4, 2.4 Hz, 1H), 3.99
(br, 1H), 2.17 (br, 1H), 1.57 (br, 1H), 0.96 (s, 9H), 0.25 (s, 3H),
(3aR,4R,7R,7aS)-7-azido-3a,4,7,7a-tetrahydro-2,2-
dimethylbenzo[d][1,3]dioxol-4-ol (22b). To a stirred
solution of ketone 21 (35 mg, 0.17 mmol, 1.0 equiv.) in
anhydrous CH2Cl2 (1.0 mL) was cooled to -78 °C and then
was slowly added DIBAL-H (diisobutylalummium hydride)
(1 M in hexane, 0.25 mL, 0.25 mmol, 1.5 equiv.) and stirred
for an additional 30 minutes at –78 oC until TLC indicated
disappearance of starting material (EtOAc : hexane = 1 : 3,
Rf startng metarial : product : diastereomer = 0.6 : 0.3 :
0.45). Upon completion, it was quenched with satd aq.
NH4Cl, diluted with EtOAc (10 mL) and washed with satd
aq. NH4Cl (3 mL) and then brine. The combined organic
layers were dried over MgSO4, filtered and concentrated in
vacuo. The resulting residue was purified by silica gel
column chromatography using EtOAc : hexane (1 : 4) as
eluents to give alcohol (product 22b as colorless oil 24 mg,
68% and diastereomer 22a as colorless oil 2.8 mg, 8%). Rf
= 0.27 (silica gel, EtOAc : hexane = 1 : 3); [α]D25 = -213o (c 0.3,
CHCl3); IR (film) νmax 3262, 2099, 1649, 1212, 1090, 894 cm-1;
1H NMR (400 MHz, CDCl3): δ 6.14 (dddd, J=10.0, 3.6, 0.8,
0.8 Hz, 1H), 5.92 (dddd, J=10.0, 4.8, 1.6 , 0.8 Hz, 1H), 4.47
(ddd, J=7.2, 4.8, 0.8 Hz, 1H), 4.36-4.32 (m, 1H), 4.31-4.25 (m,
2H), 2.57 (d, J=6.8 Hz, 1H), 1.42 (s, 3H), 1.35 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 135.3, 126.5, 109.9, 77.2, 75.3, 64.7,
58.1, 26.2, 24.5; HRMS (EI, magnetic sector) m/z: [M]+ calcd
for C9H13N3O3 211.0957; found 211.0952.
13
0.21 (s, 3H); C{1H} NMR (100 MHz, CDCl3): δ 164.4, 151.2,
148.4, 131.0, 130.4, 121.7, 121.4, 107.4, 102.5, 101.9, 73.5, 72.1,
68.9, 52.8, 25.8, 17.9, -4.0, -4.3; HRMS (FAB, magnetic
sector) m/z: [M+H]+ calcd for C20H28NO6Si 406.1686; found
406.1685.
(2S,3R,4S,4aR)-2,3,4-trihydroxy-3,4,4a,5-tetrahydro-
[1,3]dioxolo[4,5-j]phenanthridin-6(2H)-one
(+)-
lycoricidine (1). To a stirred solution of silyl ether 20 (51
mg, 0.13 mmol, 1.0 equiv.) in anhydrous THF (2 mL) was
added TBAF (tetrabutylammonium fluoride) (1 M in THF,
0.14 mL, 0.14 mmol, 1.1 equiv.) at room temperature for an
additional 3 hours until TLC indicated disappearance of
starting material (MeOH : CHCl3 = 1 : 8, Rf startng metarial
: product = 0.8 : 0.3). Upon completion, the solvent was
removed under reduced pressure and the residue was
purified by normal phase silica gel column with eluted by
MeOH : CHCl3 = 1 : 4 to give a white solid, wash with
acetone at 0 oC, collect the solid, remove acetone in vacuo
and obtain (+)-lycoricidine 1 as a white solid (29 mg, 79%).
Spectroscopic data was identical to that reported
previously.5b,c Rf = 0.30o (silica gel, MeOH : CHCl3 = 1 : 8);
[α]D20 = +181o (c 0.21, pyridine) [lit.5b [α]D24 = +204o (c 0.21,
20
20
pyridine), lit.5a [α]D = +180o (c 0.45, pyridine), lit.5e [α]D
= +182o (c 0.21, pyridine), lit.5f [α]D = +187o (c 0.50,
pyridine)]; IR (film) νmax 3371, 3347, 2917, 1644, 1471, 1122, 873
cm-1; 1H NMR (400 MHz, CD3OD): δ 7.31 (s, 1H), 7.07 (s, 1H),
6.09-6.07 (m, 1H), 5.98 (d, J=0.8 Hz, 1H, ABq), 5.96 (d, J=0.8
Hz, 1H, ABq), 4.31-4.28 (m, 1H), 4.17-4.15 (m, 1H), 3.85-3.82
22
(3aR,4S,7R,7aS)-7-azido-3a,4,7,7a-tetrahydro-2,2-
dimethylbenzo[d][1,3]dioxol-4-ol (22a). as colorless oil.
Rf = 0.45 (silica gel, EtOAc : hexane = 1 : 3); [α]D25 = -36.7o (c
0.8, CHCl3); IR (film) νmax 3442, 2109, 1649, 1380, 1260, 1213,
(m, 2H); C{1H} NMR (150 MHz, CD3OD): δ 166.6, 153.5,
13
150.1, 133.4, 132.7, 123.3, 122.8, 107.7, 104.4, 103.6, 74.4, 70.9,
70.8, 53.9; HRMS (EI, magnetic sector) m/z: [M]+ calcd for
C14H13NO6 291.0743; found 291.0740.
1
1063, 872 cm-1; H NMR (400 MHz, CDCl3): δ 5.90 (ddd,
J=10.0, 2.8, 2.8 Hz, 1H), 5.66 (ddd, J=10.0, 2.8, 2.8 Hz, 1H),
4.22-4.18 (m, 1H), 4.17-4.10 (m, 2H), 3.95-3.92 (m, 1H), 2.45
(d, J=4.8 Hz, 1H), 1.48 (s, 3H), 1.36 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 132.8, 126.1, 110.0, 79.8, 77.5, 70.9, 61.4, 27.0,
24.7; HRMS (EI, magnetic sector) m/z: [M]+ calcd for
C9H13N3O3 211.0957; found 211.0951.
(3aS,7R,7aS)-7-azido-2,2-dimethyl-7,7a-
dihydrobenzo[d][1,3]dioxol-4(3aH)-one (21). To
a
stirred solution of 1,2-azido alcohol 155a (157 mg, 0.75 mmol,
1.0 equiv.) in anhydrous CH2Cl2 (5.0 mL) was added
trifluoroacetic acid (0.5 M in CH2Cl2, 75 µL, 0.038 mmol,
(3aS,7R,7aS)-7-azido-tetrahydro-2,2-dimethylbenzo
[d][1,3]dioxol-4(3aH)-one (22c). as colorless oil. Rf = 0.48
o
0.050 equiv.) at 0 C and stirred for an additional 4 hours
at 0 oC until TLC indicated disappearance of starting
material (EtOAc : hexane = 1 : 3, Rf startng metarial : allylic
alcohol = 0.5 : 0.4). Upon completion, the reaction mixture
was added Dess-Martin periodinane (477 mg, 1.13 mmol, 1.5
equiv.) at 0 °C and stirred for an additional 30 minutes at 0
oC until TLC indicated disappearance of starting material
25
(silica gel, EtOAc : hexane = 1 : 3); [α]D = -75o (c 0.04,
1
CHCl3); IR (film) νmax 2106, 1733, 1221, 1053, 1034 cm-1; H
NMR (400 MHz, CDCl3): δ 4.44-4.41 (m, 1H), 4.37 (d, J=6.0
Hz, 1H), 4.02 (dd, J=8.8, 3.6 Hz, 1H), 2.65-2.56 (m, 1H), 2.43
(ddd, J=16.0, 5.2, 5.2 Hz, 1H), 2.25-2.16 (m, 1H), 2.10-2.03 (m,
1H), 1.44 (s, 3H), 1.37 (s, 3H); 13C{1H} NMR (100 MHz,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
(1S,2S,3R,6S)-6-acetamidocyclohex-4-ene-1,2,3-triyl
Page 8 of 14
CDCl3): δ 206.2, 111.0, 78.8, 77.8, 58.6, 34.3, 27.0, 25.7, 24.3;
HRMS (EI, magnetic sector) m/z: [M]+ calcd for C9H13N3O3
211.0957; found 211.0954.
triacetate: tetraacetyl ent-conduramine F-1 (26). A
solution of azido 25 (79 mg, 0.25 mmol, 1.0 equiv.) in
1
2
3
4
5
6
7
8
o
anhydrous ether (3.5 mL) was dropwisely added to a 0 C
(1S,2R,3R,6R)-6-acetamidocyclohex-4-ene-1,2,3-triyl
triacetate: tetraacetyl conduramine C-4 (23). A solution
of azido alcohol 22b (10 mg, 0.047 mmol, 1.0 equiv.) in
suspension consisting of LiAlH4 (48 mg, 1.25 mmol, 5.0
equiv.) in anhydrous ether (4.4 mL). After stirring 1 hour at
0 oC, a small amount of water is carefully added to destroy
the excess LiAlH4, and then a solution of HOAc : H2O (4 :
o
anhydrous ether (1.5 mL) was dropwisely added to a 0 C
suspension consisting of LiAlH4 (8.9 mg, 0.24 mmol, 5.0
equiv.) in anhydrous ether (1.5 mL). After stirring 1 hour at
0 oC, a small amount of water is carefully added to destroy
the excess LiAlH4, and then a solution of HOAc : H2O (4 :
o
1, 7.9 mL) was added and stirred at 50 C for 22 h. The
mixture was evaporated in vacuo to give ent-conduramine
F-1, which was characterized as its tetraacetate. To the
residue was added pyridine (4.7 mL) and Ac2O (2.4 mL) at
room temperature. After stirring 16 hours at room
temperature, the reaction mixture was concentrated in
vacuo, diluted with EtOAc (10 mL), filtered through a pad
of Celite and poured into satd aq. Na2CO3 (5 mL). The
aqueous layer was extracted with EtOAc (2×10 mL) and the
combined organic phases were dried over MgSO4,
concentrated. The obtained residue was purified by silica
gel column chromatography using EtOAc as eluents to give
tetraacetyl ent-conduramine F-1 26 as white soild (70 mg,
89%). Spectroscopic data was identical to that reported
previously.13a Rf = 0.51 (silica gel, EtOAc); [α]D25 = -8.6o (c
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
1, 2 mL) was added and stirred at 110 C for 22 h. The
mixture was evaporated in vacuo to give conduramine C-4,
which was characterized as its tetraacetate. To the residue
was added pyridine (0.6 mL) and Ac2O (0.3 mL) at room
temperature. After stirring 16 hours at room temperature,
the reaction mixture was concentrated in vacuo, diluted
with EtOAc (5 mL), filtered through a pad of Celite and
poured into satd aq. Na2CO3 (3 mL). The aqueous layer was
extracted with EtOAc (2×5 mL) and the combined organic
phases were dried over MgSO4, concentrated. The
obtained residue was purified by silica gel column
chromatography using EtOAc as eluents to give
conduramine C-4 tetraacetate 23 as white soild (8.6 mg,
25
0.5, CHCl3) [lit.13a [α]D = -7.1o (c = 0.15, CHCl3)]; IR (film)
1
25
νmax 3283, 1746, 1655, 1226, 1034 cm-1; H NMR (400 MHz,
58%). Rf = 0.40 (silica gel, EtOAc); [α]D = -130o (c 0.1,
1
CDCl3): δ 5.81 (ddd, J=10.0, 4.8, 1.6 Hz, 1H), 5.73 (ddd, J=10.8,
2.8, 0.4 Hz, 1H), 5.55 (d, J=8.8 Hz, 1H), 5.37 (dd, J=10.0, 6.8
Hz, 1H), 5.31-5.28 (m, 1H), 5.06 (dd, J=10.0, 4.8 Hz, 1H), 4.99
(ddd, J=9.2, 4.8, 4.8 Hz, 1H), 2.05 (s, 3H), 2.04 (s, 3H), 2.00
(s, 6H); 13C{1H} NMR (100 MHz, CDCl3): δ 170.2, 170.1, 169.9,
169.8, 128.0, 127.5, 77.2, 71.8, 68.7, 45.4, 23.3, 20.9, 20.8, 20.7;
HRMS (EI, magnetic sector) m/e calcd for C14H19NO7
313.1161; found 313.1165.
CHCl3); IR (film) νmax 2106, 1733, 1221, 1053, 1034 cm-1; H
NMR (400 MHz, CDCl3): δ 5.72 (dd, J=9.2, 2.4 Hz, 1H), 5.56-
5.54 (m, 4H), 5.04 (d, J=9.2 Hz, 1H), 4.99-4.95 (m, 1H), 2.13
(s, 3H), 2.05 (s, 3H), 2.01 (s, 3H), 1.96 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 171.0, 170.4, 170.1, 169.9, 130.0, 125.5,
70.8, 69.4, 68.0, 48.1, 23.3, 20.8 (2C), 20.7; HRMS (EI,
magnetic sector) m/z: [M]+ calcd for C14H19NO7 313.1161;
found 313.1165.
(3aS,4S,5S,7aS)-5-azido-3a,4,5,7a-tetrahydro-2,2-
(3aS,4R,7S,7aS)-7-azido-2,2-dimethyl-3a,4,7,7a-
dimethylbenzo[d][1,3]dioxol-4-ol (28). To a stirred
solution of bromohydrin 27\h (320 mg, 1.28 mmol, 1.0
equiv.) in anhydrous DMF (5.0 mL) was added sodium
azide (125 mg, 1.92 mmol, 1.5 equiv.). After stirring 12 hour
at room temperature until TLC indicated disappearance of
starting material (EtOAc : hexane = 1 : 4, Rf startng metarial
: product = 0.3 : 0.2). Upon completion, it was diluted with
EtOAc (15 mL) and washed with water (6 mL) and then
brine. The aqueous layer was extracted with EtOAc (2×10
mL) and the combined organic phases were dried over
MgSO4, concentrated in vacuo. The resulting residue was
purified by silica gel column chromatography using EtOAc
: hexane (1 : 2) as eluents to give azido 28 as colorless oil
(246 mg, 91%). Rf = 0.49 (silica gel, EtOAc : hexane = 1 : 2);
[α]D25 = -153.4o (c 3.2, CHCl3); IR (film) νmax 3450, 2987, 2102,
tetrahydrobenzo[d][1,3]dioxol-4-yl benzoate (25). A
solution of 1,4-azido alcohol 247a (100 mg, 0.47 mmol, 1.0
equiv.) in anhydrous THF (3 mL) was added a stirred
solution of PPh3 (triphenylphosphine) (206 mg, 1.18 mmol,
2.5 equiv.) in anhydrous THF (2 mL) at room temperature
followed by benzoic acid (144 mg, 1.18 mmol, 2.5 equiv.)
and DEAD (diethyl azodicarboxylate) (196 mg, 1.13 mmol,
2.4 equiv.) in THF (2 mL) were added and continued the
stirring for
2 hours until TLC analysis indicated
disappearance of starting materials (EtOAc : hexane = 1 : 2,
Rf startng metarial : product = 0.3 : 0.8). Upon completion,
The solvent was removed under reduced pressure and the
residue was purified by normal phase silica gel column
with eluted by EtOAc : hexane = 1 : 10 to give compound as
colorless oil 25 (131 mg, 87%). Rf = 0.66 (silica gel, EtOAc :
hexane = 1 : 4); [α]D25 = -48o (c 2.0, CHCl3); IR (film) νmax
1
1377, 1229, 1168, 1117, 1085, 858 cm-1; H NMR (400 MHz,
1
CDCl3): δ 6.32 (ddd, J=10.0, 2.4, 2.4 Hz, 1H), 5.60 (dddd,
J=10.0, 2.4, 2.4, 1.2 Hz, 1H), 4.67-4.61 (m, 2H), 3.95-3.92 (m,
1H), 3.50 (dd, J=8.8, 1.6 Hz, 1H), 2.65 (d, J=2.4 Hz, 1H), 1.47
(s, 3H), 1.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 129.3,
124.7, 111.0, 79.5, 71.0, 68.1, 61.1, 26.8, 26.3; HRMS (EI,
magnetic sector) m/e calcd for C9H13N3O3 211.0957; found
211.0950.
2101, 1718, 1601, 1267, 1115, 1092, 848, 711cm-1; H NMR (400
MHz, CDCl3): δ 8.07-8.05 (m, 2H), 7.58-7.54 (m, 1H), 7.45-
7.41 (m, 2H), 5.87-5.86 (m, 2H), 5.70 (d, J=8.8 Hz, 1H), 4.49
(dd, J=4.0, 4.0 Hz, 1H), 4.22 (dd, J=10.0, 8.8 Hz, 1H), 3.80
13
(dd, J=10.0, 4.0 Hz, 1H), 1.53 (s, 3H), 1.49 (s, 3H); C{1H}
NMR (100 MHz, CDCl3): δ 165.9, 133.3, 131.3, 129.9, 129.6,
128.4, 125.8, 111.7, 76.5, 73.9, 73.3, 56.4, 27.0, 26.4; HRMS (EI,
magnetic sector) m/z: [M]+ calcd for C16H17N3O4 315.1219;
found 315.1214.
(1S,2R,3S,6S)-6-acetamidocyclohex-4-ene-1,2,3-triyl
triacetate: tetraacetyl ent-conduramine C-1 (29). A
ACS Paragon Plus Environment

Page 9 of 14
The Journal of Organic Chemistry
solution of azido 28 (155 mg, 0.73 mmol, 1.0 equiv.) in
anhydrous ether (7 mL) was dropwisely added to a 0 C
(3aR,4R,7S,7aS)-7-azido-3a,4,7,7a-tetrahydro-2,2-
o
1
2
3
4
5
6
7
dimethylbenzo[d][1,3]dioxol-4-ol (31). To a stirred
solution of ketone 30 (49 mg, 0.23 mmol, 1.0 equiv.) in
anhydrous MeOH (3.0 mL) was added CeCl3·7H2O (131 mg,
0.35 mmol, 1.5 equiv.). Then, the reaction mixture was
cooled to -78 °C and NaBH4 (10.2 mg, 0.47 mmol, 2.0
equiv.) was added. After stirring for an additional 1 hours
suspension consisting of LiAlH4 (139 mg, 3.65 mmol, 5.0
equiv.) in anhydrous ether (8.5 mL). After stirring 1 hour at
0 oC, a small amount of water is carefully added to destroy
the excess LiAlH4, and then a solution of HOAc : H2O (4 :
o
1, 15.5 mL) was added and stirred at 50 C for 22 h. The
o
mixture was evaporated in vacuo to give ent-conduramine
C-1, which was characterized as its tetraacetate. To the
residue was added pyridine (9.3 mL) and Ac2O (4.7 mL) at
room temperature. After stirring 16 hours at room
temperature, the reaction mixture was concentrated in
vacuo, diluted with EtOAc (15 mL), filtered through a pad
of Celite and poured into satd aq. Na2CO3 (8 mL). The
aqueous layer was extracted with EtOAc (2×15 mL) and the
combined organic phases were dried over MgSO4,
concentrated. The obtained residue was purified by silica
gel column chromatography using EtOAc as eluents to give
tetraacetyl ent-conduramine C-1 29 as white soild (156 mg,
68%). Spectroscopic data was identical to that reported
previously.17c,11 Rf = 0.48 (silica gel, EtOAc); [α]D25 = +187o (c
1.4, CH2Cl2) [lit.11 enantiomer [α]D25 = -181o (c 1.0, CH2Cl2),
lit.7c enantiomer [α]D = -178o (c 0.995, CH2Cl2)]; IR (film)
νmax 3285, 1747, 1659, 1226 cm-1; 1H NMR (400 MHz, CDCl3):
δ 5.72 (d, J=10.4 Hz, 1H), 5.63-5.59 (m, 2H), 5.52 (bs, 2H),
5.13 (d, J=7.6 Hz, 1H), 5.05 (dd, J=5.6, 2.8 Hz, 1H), 2.11 (s,
3H), 2.05 (s, 3H), 2.01 (s, 3H), 1.96 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 170.4, 170.0, 169.7, 169.2, 129.1, 126.4, 71.5,
70.0, 68.9, 46.3, 23.2, 21.0, 20.9, 20.8; HRMS (EI, magnetic
sector) m/z: [M]+ calcd for C14H19NO7 313.1162; found
313.1164.
at –78 C until TLC indicated disappearance of starting
material (EtOAc : hexane = 1 : 2, Rf startng metarial : allylic
alcohol = 0.5 : 0.1). Upon completion, the reaction mixture
was quenched with satd aq. NH4Cl, diluted with EtOAc (10
mL) and washed with satd aq. NH4Cl (3 mL) and then
brine. The combined organic layers were dried over
MgSO4, filtered and concentrated in vacuo. The resulting
residue was purified by silica gel column chromatography
using EtOAc : hexane (1 : 1.5) as eluents to give alcohol 31
as white soild (45 mg, 91%). Rf = 0.45 (silica gel, EtOAc :
hexane = 1 : 1); [α]D25 = -37.5o (c 0.4, CHCl3); IR (film) νmax
3420, 2105, 1649, 1381, 1080, 1250, 1211, 1167, 857 cm-1; 1H NMR
(400 MHz, CDCl3): δ 5.91-5.87 (m, 1H), 5.77-5.73 (m, 1H),
4.64 (ddd, J=7.6, 4.0, 2.0 Hz, 1H), 4.55 (ddd, J=7.6, 4.4, 2.0
Hz, 1H), 3.96 (ddd, J=10.8, 4.8, 2.4 Hz, 1H), 3.56 (dd, J=2.8,
2.8 Hz, 1H), 2.55 (d, J=10.8 Hz, 1H), 1.38 (s, 3H), 1.36 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 133.8, 124.8, 110.2, 75.6,
75.5, 66.7, 56.7, 25.5, 24.7; HRMS (EI, magnetic sector) m/z:
[M]+ calcd for C9H13N3O3 211.0957; found 211.0950.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(1S,2R,3R,6S)-6-acetamidocyclohex-4-ene-1,2,3-triyl
triacetate: tetraacetyl conduramine D-1 (32). A solution
of azido 31 (35 mg, 0.17 mmol, 1.0 equiv.) in anhydrous
o
ether (2 mL) was dropwisely added to a 0 C suspension
consisting of LiAlH4 (31.5 mg, 0.83 mmol, 5.0 equiv.) in
o
(3aS,7S,7aS)-7-azido-7,7a-dihydro-2,2-dimethylbenzo
[d][1,3]dioxol-4(3aH)-one (30). To a stirred solution of
1,2-azido alcohol 28 (135 mg, 0.64 mmol, 1.0 equiv.) in
anhydrous CH2Cl2 (4.5 mL) was added trifluoroacetic acid
(0.5 M in CH2Cl2, 51 µL, 0.026 mmol, 0.040 equiv.) at 0 oC
anhydrous ether (3.3 mL). After stirring 1 hour at 0 C, a
small amount of water is carefully added to destroy the
excess LiAlH4, and then a solution of HOAc : H2O (4 : 1, 5.3
mL) was added and stirred at 110 oC for 22 h. The mixture
was evaporated in vacuo to give conduramine D-1, which
was characterized as its tetraacetate. To the residue was
added pyridine (3.2 mL) and Ac2O (1.6 mL) at room
temperature. After stirring 16 hours at room temperature,
the reaction mixture was concentrated in vacuo, diluted
with EtOAc (10 mL), filtered through a pad of Celite and
poured into satd aq. Na2CO3 (5 mL). The aqueous layer was
extracted with EtOAc (2×10 mL) and the combined organic
phases were dried over MgSO4, concentrated. The
obtained residue was purified by silica gel column
chromatography using EtOAc as eluents to give tetraacetyl
conduramine D-1 32 as white soild (32 mg, 62%).
Spectroscopic data was identical to that reported
previously, but the optical rotation value is not identical.7c,9
So, we have provided corrected optical rotation value. Rf =
o
and stirred for an additional 2 hours at 10 C until TLC
indicated disappearance of starting material (EtOAc :
hexane = 1 : 2, Rf startng metarial : allylic alcohol = 0.5 : 0.3).
Upon completion, the reaction mixture was added Dess-
Martin periodinane (406 mg, 0.96 mmol, 1.5 equiv.) at 0 °C
and stirred for an additional 30 minutes at 0 oC until TLC
indicated disappearance of starting material (EtOAc :
hexane = 1 : 2, Rf allylic alcohol : product = 0.3 : 0.5). Upon
completion, the solution was filtered through a pad of
Celite, concentrated. The obtained residue was purified by
silica gel column chromatography using EtOAc : hexane (1
: 3) as eluents to give α,β-unsaturated ketone 30 as
colorless oil (88 mg, 66%). Rf = 0.47 (silica gel, EtOAc :
hexane = 1 : 2); [α]D25 = +183o (c 0.3, CHCl3); IR (film) νmax
2103, 1684, 1649, 1377, 1229, 1109, 1066, 1046, 838, 773 cm-1;
1H NMR (400 MHz, CDCl3): δ 6.81 (ddd, J=10.4, 2.4, 2.4 Hz,
1H), 6.22 (dd, J=10.4, 2.4 Hz, 1H), 4.79 (ddd, J=6.8, 2.4, 2.4
Hz, 1H), 4.35-4.32 (m, 1H), 4.31 (d, J=5.2 Hz, 1H), 1.42 (s, 3H),
1.34 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 194.5, 144.4,
129.8, 111.1, 75.7, 75.2, 55.5, 27.2, 26.0; HRMS (EI, magnetic
sector) m/z: [M]+ calcd for C9H11N3O3 209.0801; found
209.0806.
25
0.36 (silica gel, EtOAc); [α]D = -50o (c 0.4, CHCl3) [lit.9
enantiomer [α]D25 +14.13o (c 1.0, CHCl3)]; IR (film) νmax 3361,
1
1741, 1651, 1229 cm-1; H NMR (400 MHz, CDCl3): δ 5.84
(ddd, J=10.0, 4.4, 2.0 Hz, 1H), 5.74-5.68 (m, 2H), 5.55-5.52
(m, 1H), 5.49 (bs, 1H), 5.20 (dd, J=5.6, 2.0 Hz, 1H), 4.98 (ddd,
J=10.0, 5.6, 5.6 Hz, 1H), 2.12 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H),
1.99 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 169.7, 169.5,
169.3, 169.2, 128.7, 126.3, 68.9, 67.0, 66.7, 44.7, 23.3, 20.9,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
20.7, 20.6; HRMS (EI, magnetic sector) m/z: [M]+ calcd for
Page 10 of 14
128.4, 127.7, 112.1, 78.3, 77.7, 72.7, 61.2, 26.9(2C); HRMS (EI,
magnetic sector) m/z: [M]+ calcd for C16H17N3O4 315.1220;
found 315.1216.
1
2
3
4
5
6
7
8
C14H19NO7 313.1162; found 313.1151.
(3aS,4S,7R,7aS)-3a,4,7,7a-tetrahydro-4-hydroxy-2,2-
dimethylbenzo[d][1,3]dioxol -7-yl benzoate (33). To a
stirred solution of Pd(PPh3)4 [tetrakis(triphenylphosphine)
palladium(0)] (40.5 mg, 0.035 mmol, 0.020 equiv.) and
benzoic acid (144 mg, 1.18 mmol, 2.5 equiv.) in anhydrous
THF (5 mL) was added at 0 oC a solution of allylic epoxide
1010h (295 mg, 1.75 mmol, 1.0 equiv.) in anhydrous THF (5
mL). After stirring 30 minutes at 0 oC until TLC indicated
disappearance of starting material (EtOAc : hexane = 1 : 4,
Rf startng metarial : product = 0.6 : 0.2). Upon completion,
it was diluted with EtOAc (20 mL) and washed with water
(6 mL) and then brine. The aqueous layer was extracted
with EtOAc (2×15 mL) and the combined organic phases
were dried over MgSO4, concentrated in vacuo. The
resulting residue was purified by silica gel column
chromatography using EtOAc : hexane (1 : 2) as eluents to
give alcohol 33 (484 mg, 95%). Rf = 0.34 (silica gel, EtOAc :
hexane = 1 : 2); [α]D25 = -64o (c 2.0, CHCl3); IR (film) νmax
3473, 1721, 1601, 1270, 1090, 849, 817, 713 cm-1; 1H NMR (400
MHz, CDCl3): δ 8.07-8.04 (m, 2H), 7.57-7.52 (m, 1H), 7.44-
7.40 (m, 2H), 6.00 (ddd, J=10.0, 5.2, 5.2, 2.0 Hz, 1H), 5.84
(dd, J=10.0, 2.0 Hz, 1H), 5.74-5.70 (m, 1H), 4.58 (dd, J=4.0,
4.0 Hz, 1H), 4.25 (dd, J=10.0, 8.8 Hz, 1H), 3.62 (dd, J=10.0,
(1S,2S,3R,6R)-6-acetamidocyclohex-4-ene-1,2,3-triyl
triacetate: tetraacetyl conduramine B-1 (36). A solution
of azido 35 (50 mg, 0.16 mmol, 1.0 equiv.) in anhydrous
o
ether (2 mL) was dropwisely added to a 0 C suspension
consisting of LiAlH4 (30 mg, 0.79 mmol, 5.0 equiv.) in
anhydrous ether (3 mL). After stirring 1 hour at 0 oC, a small
amount of water is carefully added to destroy the excess
LiAlH4, and then a solution of HOAc : H2O (4 : 1, 5 mL) was
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
added and stirred at 50 C for 22 h. The mixture was
evaporated in vacuo to give conduramine B-1, which was
characterized as its tetraacetate. To the residue was added
pyridine (3 mL) and Ac2O (1.5 mL) at room temperature.
After stirring 16 hours at room temperature, the reaction
mixture was concentrated in vacuo, diluted with EtOAc (10
mL), filtered through a pad of Celite and poured into satd
aq. Na2CO3 (5 mL). The aqueous layer was extracted with
EtOAc (2×10 mL) and the combined organic phases were
dried over MgSO4, concentrated. The obtained residue was
purified by silica gel column chromatography using EtOAc
as eluents to give tetraacetyl conduramine B-1 36 as white
soild (33.3 mg, 67%). Spectroscopic data was identical to
that reported previously.8a Rf = 0.53 (silica gel, EtOAc);
[α]D25 =-156o (c 0.6, CHCl3) [lit.8a [α]D = -169o ]; IR (film) νmax
3283, 1751, 1659, 1224 cm-1; 1H NMR (400 MHz, CDCl3): δ 5.71
(d, J=8.4 Hz, 1H), 5.67-5.58 (m, 2H), 5.54-5.51 (m, 1H), 5.35
(dd, J=10.8, 8.0 Hz, 1H), 5.05 (dd, J=10.8, 9.2 Hz, 1H), 4.87-
13
3.6 Hz, 1H), 2.47 (bs, 1H), 1.48 (s, 6H); C{1H} NMR (100
MHz, CDCl3): δ 166.0, 133.2, 130.6, 129.9, 129.8, 128.8, 128.3,
111.2, 76.9, 73.6, 73.1, 64.1, 27.1, 26.7; HRMS (ESI, magnetic
sector) m/z: [M+H]+ calcd for C16H20O5 291.1227; found
291.1218.
13
4.81 (m, 1H), 2.03 (s, 6H), 2.01 (s, 3H), 1.93 (s, 3H); C{1H}
NMR (100 MHz, CDCl3): δ 171.1, 170.3, 169.9, 169.6, 129.7,
125.9, 71.9, 71.7, 71.4, 50.9, 23.1, 20.8, 20.6, 20.5; HRMS (EI,
magnetic sector) m/z: [M]+ calcd for C14H19NO7 313.1162;
found 313.1165.
(3aS,4R,7R,7aS)-4-azido-3a,4,7,7a-tetrahydro-2,2-
dimethylbenzo[d][1,3]dioxol-7-yl benzoate (35). To a
stirred solution of allylic alcohol 33 (138 mg, 0.48 mmol, 1.0
equiv.) in anhydrous DMF (2.0 mL) was added Et3N (0.12
mL, 0.71 mmol, 1.5 equiv.) and MsCl (methanesulfonyl
chloride) (44 µL, 0.57 mmol, 1.2 equiv.) at 0 oC and stirred
N-((3aS,4R,7S,7aS)-7-hydroxy-2,2-dimethyl-3a,4,7,7a-
tetrahydrobenzo[d][1,3]dioxol-4-yl)-4-
methylbenzenesulfonamide (34). To a stirred solution
of Pd(PPh3)4 [tetrakis(triphenylphosphine) palladium(0)]
(34 mg, 0.029 mmol, 0.050 equiv.), NaNHTs (172 mg, 0.89
mmol, 1.5 equiv.) and NH2Ts (102 mg, 0.59 mmol, 1.0
o
for an additional 20 minutes at 0 C until TLC indicated
disappearance of starting material (EtOAc : hexane = 1 : 4,
Rf startng metarial : allylic alcohol = 0.2 : 0.7). Upon
completion, the reaction mixture was added sodium azide
o
o
(62 mg, 0.95 mmol, 2 equiv.) at 0 C and then allowed to
equiv.) in anhydrous THF (4 mL) was added at 0 C a
stir to room temperature for 2 hours until TLC indicated
disappearance of starting material (EtOAc : hexane = 1 : 4,
Rf startng metarial : allylic alcohol = 0.7 : 0.65). Upon
completion, it was diluted with EtOAc (15 mL) and washed
with water (6 mL) and then brine. The aqueous layer was
extracted with EtOAc (2×10 mL) and the combined organic
phases were dried over MgSO4, concentrated in vacuo. The
resulting residue was purified by silica gel column
chromatography using EtOAc : hexane (1 : 10) as eluents to
give azido 35 as white soild (132 mg, 88%). Rf = 0.65 (silica
gel, EtOAc : hexane = 1 : 4); [α]D25 = -231o (c 2.0, CHCl3); IR
(film) νmax 2104, 1722, 1602, 1269, 1134, 1096, 1026, 974, 851,
solution of allylic epoxide 107h (100 mg, 0.59 mmol, 1.0
equiv.) in anhydrous THF (5 mL). The reaction mixture
allowed to stir to room temperature for 30 hours until TLC
indicated disappearance of starting material (EtOAc :
hexane = 1 : 4, Rf startng metarial : product : side product =
0.6 : 0 : 0.2). Upon completion, it was diluted with EtOAc
(15 mL) and washed with satd aq. NH4Cl (5 mL) and then
brine. The aqueous layer was extracted with EtOAc (2×10
mL) and the combined organic phases were dried over
MgSO4, concentrated in vacuo. The resulting residue was
purified by silica gel column chromatography using EtOAc
: hexane (1 : 1) as eluents to give (tosylamide product 34 as
slight yellow soild 139 mg, 69% and side protuct as white
soild 34a 7.9 mg, 8%). Rf = 0.15 (silica gel, EtOAc : hexane
= 1 : 1); [α]D25 = +35o (c 0.6 , CHCl3); IR (film) νmax 3445, 3284,
2986, 2899, 1631, 1599, 1451, 1374, 1330, 1230, 1159, 1135, 1088,
1
712 cm-1; H NMR (400 MHz, CDCl3): δ 8.07-8.04 (m, 2H),
7.58-7.54 (m, 1H), 7.45-7.41 (m, 2H), 5.84 (ddd, J=10.0, 2.0,
2.0 Hz, 1H), 5.80-5.76 (m, 1H), 5.72 (ddd, J=10.0, 2.0, 2.0 Hz,
1H), 4.24 (ddd, J=8.8, 4.8, 2.4 Hz, 1H), 3.89 (dd, J=10.0, 8.8
Hz, 1H), 3.70 (dd, J=9.2, 9.2 Hz, 1H), 1.48 (s, 6H); C{1H}
815 cm-1; H NMR (400 MHz, CDCl3): δ 7.76 (d, J=8.4 Hz,
13
1
NMR (100 MHz, CDCl3): δ 165.8, 133.3, 129.8, 129.6, 129.2,
2H), 7.26 (d, J=8.4 Hz, 2H), 5.81 (ddd, J=10.0, 5.2, 2.4 Hz,
ACS Paragon Plus Environment

Page 11 of 14
The Journal of Organic Chemistry
1H), 5.54 (dd, J=10.0, 2.0 Hz, 1H), 5.19 (d, J=8.8 Hz, 1H), 4.43
acid (0.5 M in CH2Cl2, 0.27 mL, 0.14 mmol, 0.060 equiv.)
and stirred for an additional 30 hours at 50 C until TLC
o
1
2
3
4
5
6
7
8
(ddd, J=5.2, 3.2, 3.2 Hz, 1H), 4.02 (dd, J=8.8, 8.8 Hz, 1H),
3.69 (dd, J=9.6, 9.6 Hz, 1H), 3.36 (dd, J=9.6, 3.2 Hz, 1H), 2.62
(bs, 1H), 2.40(s, 3H), 1.33 (s, 3H), 1.28 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 143.3, 138.1, 132.3, 129.4, 128.2, 127.2,
110.7, 77.6, 73.6, 63.8, 55.9, 27.0, 26.4, 21.5; HRMS (ESI,
magnetic sector) m/z: [M+H]+ calcd for C16H22NO5S
340.1213; found 340.1200.
indicated disappearance of starting material (EtOAc :
hexane = 1 : 2, Rf startng metarial : alcohol = 0.34 : 0.3).
Upon completion, the reaction mixture was added Dess-
Martin periodinane (5.73 mg, 13.5 mmol, 5 equiv.) at 0 °C
and stirred for an additional 15 hours at room temperature
until TLC indicated disappearance of starting material
(EtOAc : hexane = 1 : 2, Rf allylic alcohol : product = 0.3 :
0.5). Upon completion, the solution was filtered through a
pad of Celite, concentrated. The obtained residue was
purified by silica gel column chromatography using EtOAc
: hexane (1 : 3) as eluents to give ketone 37 as white soild
(455 mg, 71%). Rf = 0.45 (silica gel, EtOAc : hexane = 1 : 2);
[α]D25 = -30.8o (c 0.8, CHCl3); IR (film) νmax 1756, 1724, 1646,
(3aS,4S)-2,2-dimethyl-3a,4-dihydrobenzo[d][1,3]dioxol
-4-ol (34a). Rf = 0.24 (silica gel, EtOAc : hexane = 1 : 4);
[α]D25 = +416 (c 1.1 , CHCl3); IR (film) νmax 3420, 1685, 1650,
1386, 1223, 1073 cm-1; 1H NMR (400 MHz, CDCl3): δ 6.16 (dd,
J=9.6, 5.6 Hz, 1H), 5.71-5.67 (m, 1H), 5.04 (dd, J=5.2, 2.0 Hz,
1H), 4.66 (ddd, J=5.2, 1.6, 0.8 Hz, 1H), 4.21-4.17 (m, 1H), 1.81
(d, J=4.4 Hz, 1H), 1.61 (s, 3H), 1.51 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 154.1, 129.5, 117.0, 114.4, 87.9, 77.9, 62.8, 26.7,
24.6; HRMS (EI, magnetic sector) m/z: [M]+ calcd for
C9H12O3 168.0786; found 168.0776.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
1282, 1245, 1123, 1093, 1067, 711 cm-1; H NMR (400 MHz,
CDCl3): δ 8.10-8.08 (m, 2H), 7.60-7.55 (m, 1H), 7.46-7.42 (m,
2H), 6.18-6.11 (m, 2H), 6.07-6.04 (m, 1H), 5.16 (ddd, J=7.2,
3.6, 1.6 Hz, 1H), 4.89 (d, J=6.8 Hz, 1H), 1.51 (s, 3H), 1.42 (s,
(1S,2S,3S,6R)-6-acetamidocyclohex-4-ene-1,2,3-triyl
triacetate : tetraacetyl ent-conduramine F-4 (40).
Small pieces of sodium (72 mg, 3.2 mmol, 10 equiv.) were
added to a solution of tosylamide 34 (112 mg, 0.33 mmol, 1.0
equiv.) in THF (2 mL) and liquid ammonia (10 mL) at –78
°C until the blue color persisted. The mixture was stirred
for 45 minutes at - 78 °C, and a small amount of NH4Cl (100
mg) was then carefully added to destroy the excess amount
of sodium. The reaction mixture was slowly warmed to
room temperature for overnight and then concentrated in
vacuo and then a solution of HOAc : H2O (4 : 1, 5 mL) was
13
3H); C{1H} NMR (100 MHz, CDCl3): δ 197.3, 165.2, 133.4,
130.5, 129.8, 128.9, 128.3, 126.0, 112.0, 77.7, 77.1, 72.6, 26.9,
25.7; HRMS (EI, magnetic sector) m/z: [M]+ calcd for
C16H16O5 288.0998; found 288.0992.
(3aS,5R,7aS)-2,2-dimethyl-5,7a-dihydro-3aH-spiro
[benzo[d][1,3]dioxole-4,2’-oxirane]-5-yl benzoate (38).
To a stirred solution of ketone 37 (82 mg, 0.28 mmol, 1.0
equiv.) in anhydrous MeOH (5.0 mL) at room temperature
was added CH2N2 in ether until the reaction mixture
converted to yellow color and stirred for an additional 20
minutes. The solvent was removed under reduced pressure
and the obtained residue was purified by silica gel column
chromatography using EtOAc : hexane (1 : 10) as eluents to
give epoxide 38 as white soild (60 mg, 70%). Rf = 0.41 (silica
gel, EtOAc : hexane = 1 : 5); [α]D25 = -137.5o (c 0.8, CHCl3); IR
o
added and stirred at 50 C for 18 h. The mixture was
evaporated in vacuo to give ent-conduramine F-4, which
was characterized as its tetraacetate. To the residue was
added pyridine (4 mL), Ac2O (2 mL) and DMAP (4-
dimethylaminopyridine) (10 mg, 0.080 mmol, 0.25 equiv.)
at room temperature. After stirring 18 hours at room
temperature, the reaction mixture was concentrated in
vacuo, diluted with EtOAc (20 mL), filtered through a pad
of Celite and poured into satd aq. NaHCO3 (5 mL). The
aqueous layer was extracted with EtOAc (2×10 mL) and the
combined organic phases were dried over MgSO4,
concentrated. The obtained residue was purified by silica
gel column chromatography using EtOAc as eluents to give
tetraacetyl ent-conduramine F-4 40 as white soild (85 mg,
82%). Spectroscopic data was identical to that reported
previously.14c Rf = 0.46 (silica gel, EtOAc); [α]D25 = +86o (c
0.06, CHCl3) [lit.14c [α]D25 = +81o (c 1.0, CHCl3)]; IR (film) νmax
1
(film) νmax 1719, 1650, 1601, 1262, 1111, 1058, 824, 711 cm-1; H
NMR (400 MHz, CDCl3): δ 8.03-8.00 (m, 2H), 7.57-7.53 (m,
1H), 7.44-7.40 (m, 2H), 6.06-5.97 (m, 2H), 5.37-5.36 (m, 1H),
4.87-4.85 (m, 1H), 4.07 (d, J=6.4 Hz, 1H), 3.10 (d, J=4.8 Hz,
1H), 3.01 (d, J=4.8 Hz, 1H), 1.52 (s, 3H), 1.39 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 165.6, 133.2, 129.8(2C), 129.7,
128.4, 126.7, 111.0, 75.1, 72.7, 68.3, 56.0, 49.6, 27.4, 26.1;
HRMS (EI, magnetic sector) m/z: [M]+ calcd for C17H18O5
302.1155; found 302.1151.
(1R,2S,3S,4S)-2-methylcyclohex-5-ene-1,2,3,4-tetraol
(39). A solution of epoxide 38 (60 mg, 0.20 mmol, 1.0
equiv.) in anhydrous ether (1.5 mL) was dropwisely added
1
o
3380, 1744, 1658, 1543, 1371, 1226, 1043 cm-1; H NMR (400
to a 0 C suspension consisting of LiAlH4 (38 mg, 0.99
MHz, CDCl3): δ 5.80-5.79 (m, 2H), 5.72 (d, J=8.4 Hz, 1H),
5.61 (dd, J=3.6, 3.6 Hz, 1H), 5.27 (dd, J=11.2, 8.4 Hz, 1H), 5.16
(dd, J=11.2, 4.0 Hz, 1H), 4.76 (dd, J=8.4, 8.4 Hz, 1H), 2.07 (s,
3H), 2.06 (s, 3H), 2.00 (s, 3H), 1.96 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 171.4, 170.1, 169.9, 169.6, 132.9, 123.9, 69.5,
68.8, 66.0, 51.5, 23.2, 20.9, 20.8, 20.6; HRMS (ESI, magnetic
sector) m/z: [M+H]+ calcd for C14H20NO7 314.1234; found
314.1217.
mmol, 5.0 equiv.) in anhydrous ether (1 mL). After stirring
o
1 hour at 0 C, a small amount of water is carefully added
to destroy the excess LiAlH4, and then a solution of HOAc
: H2O (4 : 1, 2 mL) was added and stirred at 110 oC for 22 h.
The solution was filtered through a pad of Celite, washed
with MeOH (3×5 mL), concentrated. The obtained residue
was purified by silica gel column chromatography using
MeOH : CH2Cl2 (1 : 5) as eluents to give tetraol 39 as white
soild (29 mg, 91%). Spectroscopic data was identical to that
reported previously.17a Rf = 0.52 (silica gel, MeOH：EtOAc
= 1：3); [α]D25 = +20o (c 0.2, CH3OH) [lit.17a [α]D25 = +15.5o (c
(3aS,5R,7aS)-3a,4,5,7a-tetrahydro-2,2-dimethyl-4-
oxobenzo[d][1,3]dioxol-5-yl benzoate (37). To a stirred
solution of allylic alcohol 33 (649 mg, 2.25 mmol, 1.0 equiv.)
in anhydrous CH2Cl2 (20.0 mL) was added trifluoroacetic
2.6, CH3OH)]; IR (film) νmax 3420, 1699, 1650, 1095, 1032 cm-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 14
1
1; H NMR (400 MHz, CD3OD): δ 5.74 (ddd, J=10.4, 3.2, 1.6
Functionalization of Benzene. J. Am. Chem. Soc., 2019, 141, 657 and
the references cited therein.
1
2
3
4
5
6
7
8
Hz, 1H), 5.70-5.66 (m, 1H), 4.33-4.30 (m, 1H), 3.76-3.74 (m,
(6) (a) Paul, B. J.; Willis, J.; Martinot, T. A.; Ghiviriga, I.; Abboud,
K. A.; Hudlicky, T. Synthesis, Structure, and Biological Evaluation
of Novel N- and O-Linked Diinositols. J. Am. Chem. Soc., 2002,
124, 10416. (b) Łysek, R.; Schütz, C.; Vogel, P. Total asymmetric
synthesis of (−)-conduramine B-1 and of its enantiomer. N-Benzyl
derivatives of conduramine B-1 are β-glucosidase inhibitors.
Bioorg. Med. Chem. Lett., 2005, 15, 3071. (c) Łysek, R.; Favre, S.;
Vogel, P. Conduramine F-1 epoxides: synthesis and their
glycosidase inhibitory activities. Tetrahedron, 2007, 63, 6558.
(7) (a) Chang, Y.-K.; Lo, H.-J.; Yan, T.-H. A Flexible Strategy Based
on a C2-Symmetric Pool of Chiral Substrates: Concise Synthesis of
(+)-Valienamine, Key Intermediate of (+)- Pancratistatin, and
Conduramines A-1 and E. Org. Lett., 2009, 11, 4278. (b) Leung-
Toung, R.; Liu, Y.; Muchowski, J. M.; Wu, Y.-L. Synthesis of (±)-
conduramines from pyrrole. Tetrahedron Lett., 1994, 35, 1639. (c)
Leung-Toung, R.; Y. Liu, Muchowski, J. M.; Wu, Y.-L. Synthesis of
Conduramines from N-tert-Butoxycarbonylpyrrole. J. Org. Chem.,
1998, 63, 3235. (d) Norsikian, S.; Soulé, J.-F.; Cannillo, A.; Guillot,
R.; Dau, M.-E. T. H.; Beau, J.-M. Remarkable Stereoselectivity in
Intramolecular Borono-Mannich Reactions: Synthesis of
Conduramines. Org. Lett., 2012, 14, 544. (e) Myeong, I.-S.; Kim, J.-
S.; Lee, Y.-T.; Kang, J.-C.; Park, S.-H.; Jung, C.; Ham, W.-H.
Asymmetric total synthesis of (−)-conduramine A-1 via a chiral
syn,anti-oxazine. Tetrahedron: Asymmetry, 2016, 27, 823. (f) Lu,
P.-H.; Yang, C.-S.; Devendar, B.; Liao, C.-C. Syntheses of Optically
Pure Conduramines via the Strategy of Hetero Diels−Alder
Reaction of Masked o-Benzoquinones with Homochiral Nitroso
Dienophiles. Org. Lett., 2010, 12, 2642. (g) Southgate, E. H.;
Pospech, J.; Fu, J.; Holycross, D. R.; Sarlah, D. Dearomative
dihydroxylation with arenophiles. Nat. Chem., 2016, 8, 922. (h)
Chang, Y.-K.; Lo, H.-J.; Yan, T.-H. Efficient Synthesis of Optically
Pure (+)-Bezene Diol Epoxide and (+)-Conduramine A-1. J. Chin.
Chem. Soc., 2010, 57, 24.
1H), 3.58 (dd, J=4.8, 0.8 Hz, 1H), 1.31 (s, 3H); C{1H} NMR
13
(100 MHz, CD3OD): δ 131.1, 129.5, 75.2, 74.2, 74.1, 68.0, 20.8;
HRMS (EI, magnetic sector) m/z: [M]+ calcd for C7H12O4
160.0736; found 160.0733.
ASSOCIATED CONTENT
9
Supporting Information: The Supporting Information is
available free of charge on the ACS publications website
http://pubs.acs.org. (Copies of NMR spectra for all new
compound).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
AUTHOR INFORMATION
Corresponding Author
* thyan@mail.nchu.edu.tw
Author Contributions
†H.-J. Lo and Y.-K. Chang contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the Ministry of Science and Technology of the
Republic of China for generous support.
REFERENCES
(1) Jin, Z. Amaryllidaceae and Sceletium alkaloids Nat. Prod. Rep.,
2003, 20, 606.
(2) (a) Kornienko, A.; Evidente, A. Chemistry, Biology, and
Medicinal Potential of Narciclasine and its Congeners. Chem.
Rev., 2008, 108, 1982. (b) He, M.; Qu, C.; Gao, O.; Hu, X.; Hong, X.
Biological and pharmacological activities of amaryllidaceae
alkaloids. RSC Adv. 2015, 5, 16562. (c) Fürst, R. Narciclasine - an
Amaryllidaceae Alkaloid with Potent Antitumor and Anti-
Inflammatory Properties. Planta Med., 2016, 82, 1389. (d) Ghavre,
M.; Froese, J.; Pour, M.; Hudlicky, T. Synthesis of Amaryllidaceae
Constituents and Unnatural Derivatives. Angew. Chem. Int. Ed.,
2016, 55, 5642.
(3) Okamoto, T.; Torii, Y.; Isogai, Y. O. Lycoricidinol and
lycoricidine, new plant-growth regulators in the bulbs of Lycoris
radiata herb. Chem. Pharm. Bull., 1968, 16, 1860.
(4) Ohta, S.; Kimoto, S. Synthetic Studies on Lycoricidine and
Related Compounds. II. Total Synthesis of (±)-Lycoricidine.
Chem. Pharm. Bull., 1976, 24, 2977.
(8) (a) McDonough, M. J.; Stick, R. V.; Tilbrook, D. M. G. A
Synthesis of Conduramine
B and a 'Condurithiol', useful
Molecules for Studying the Inhibition of β-Xylosidases. Aust. J.
Chem., 1999, 52, 143. (b) Raghavan, S.; Chiluveru, R. K.;
Subramanian, S. G. Stereoselective Formal Synthesis of (+)- and
(−)-Cyclophellitol and (−)-Conduritol-B and Synthesis of (−)-
Conduramine-B Derivative Using a Sulfinyl Moiety for C–O Bond
Formation and α-Chloro Sulfide for C–C Bond Formation. J. Org.
Chem., 2016, 81, 4252.
(9) Rajender, A.; Rao, B. V. Stereoselective synthesis of (−)-
conduramine C-1 and (−)-conduramine D-1. Tetrahedron Lett.,
2013, 54, 2329.
(10) Katakam, R.; Anugula, R.; Macha, L.; Batchu, V. R.
Stereoselective synthesis of N-benzyl conduramine F-1, N-benzyl
ent-conduramine E-1, dihydroconduramine F-1 and ent-
dihydroconduramine E-1. Tetrahedron Lett., 2017, 58, 559.
(11) Allemann, S.; Vogel, P. Enantioselective synthesis of
(−)-conduramine C1 and aminobromocyclitol derivatives. Helv.
Chim. Acta, 1994, 77, 1.
(12) Bellomo, A.; Giacomini, C.; Brena, B.; Seoane, G.; Gonzalez,
D. Chemoenzymatic Synthesis and Biological Evaluation of
(−)-Conduramine C-4. Synth. Commun., 2007, 37, 3509.
(13) (a) Knapp, S.; Naughton, A. B. J.; Dhar, T. G. M.
Intramolecular amino delivery reactions for the synthesis of
valienamine and analogues. Tetrahedron Lett., 1992, 33, 1025. (b)
Pandey, G. K.; Tiwari N.; Puranik, V. G. Use of Enantiomerically
Pure 7-Azabicyclo[2.2.1]heptan-2-ol as a Chiral Template for the
Synthesis of Aminocyclitols. Org. Lett., 2008, 10, 3611. (c) Kim, J.-
S.; Kang, J.-C.; Yoo, G.-H.; Jin, X.; Myeong, I.-S.; Oh, C.-Y.; Ham,
W.-H. Stereoselective total synthesis of (−)-conduramine F-1 via
chiral 1,3-oxazine. Tetrahedron, 2015, 71, 2772. (d) Prasad, K. R.;
(5) (a) Paulsen, H.; Stubbe, M. Chirale synthese von (+)-
lycoricidin. Tetrahedron Lett., 1982, 23, 3171. (b) Chida, N.;
Ohtsuka, M.; Ogawa, S. Total synthesis of (+)-lycoricidine and its
2-epimer from D-glucose. J. Org. Chem., 1993, 58, 4441. (c) Elango,
S.; Yan, T.-H. A short synthesis of (+)-lycoricidine. Tetrahedron,
2002, 58, 7335. (d) Zhang, H.; Padwa, A. An Efficient Synthesis of
(±)-Lycoricidine Featuring
a
Stille−IMDAF Cycloaddition
Cascade. Org. Lett., 2006, 8, 247. (e) Yadav, J. S.; Satheesh, G.;
Murthy, C. V. S. R. Synthesis of (+)-Lycoricidine by the
Application of Oxidative and Regioselective Ring-Opening of
Aziridines. Org. Lett., 2010, 12, 2544. (f) Saidhareddy, P.; Shaw, A.
K. Chiron approach to the total synthesis of Amaryllidaceae
alkaloid (+)-lycoricidine. Tetrahedron, 2017, 73, 6773. (g)
Bingham, T. W.; Hernandez, L. W.; Olson, D. G. R.; Svec, L.;
Hergenrother, P. J.; Sarlah, D. Enantioselective Synthesis of
Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative
ACS Paragon Plus Environment

Page 13 of 14
The Journal of Organic Chemistry
Rangari, V. A. Efficient enantiospecific synthesis of ent-
conduramine F-1. Tetrahedron, 2018, 74, 6689.
Conduritol Derivatives Reveals Superior RCM Activity.
Tetrahedron, 2000, 56, 2195.
1
2
3
4
5
6
7
8
(14) (a) Kuno, S.; Higaki, K.; Takahashi, A.; Nanba, E.; Ogawa, S.
Potent chemical chaperone compounds for GM1-gangliosidosis:
N-substituted (+)-conduramine F-4 derivatives. MedChemComm,
2015, 6, 306. (b) Seçen, H.; Gültekin, S.; Sütbeyaz, Y.; Balci, M.
Stereospecific Synthesis of Conduramine-F4 and Conduritol-F
(Leucanthemitol) Synth. Commun., 1994, 24, 2103. (c) Noritaka, C.;
Noboru, S.; Katsuyuki, M.; Takahiko, T.; Toshihiko N.; Seiichiro,
O. Total Synthesis of Acanthacerebroside A and Astrocerebroside
A via a Chiral Epoxide Intermediate Derived from L-Quebrachitol.
Bull. Chem. Soc. Jpn., 1998, 71, 259. (d) Harit, V. K.; Ramesh, N. G.
(20) Lv, P.; Huang, K.; Xie, L.; Xu, X. Palladium-catalyzed tandem
reaction to construct benzo[c]phenanthridine: application to the
total synthesis of benzo[c]phenanthridine alkaloids. Org. Biomol.
Chem., 2011, 9, 3133.
(21) Abelman, M. M.; Oh T.; Overman, L. E. Intramolecular alkene
arylations for rapid assembly of polycyclic systems containing
quaternary centers. A new synthesis of spirooxindoles and other
fused and bridged ring systems. J. Org. Chem., 1987, 52, 4130.
(22) Stafford, J. A.; Brackeen, M. F.; Karanewsky D. S.; Valvano, N.
L. A highly selective protocol for the deprotection of BOC-
protected amides and carbamates. Tetrahedron Lett., 1993, 34,
7873.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
A Chiron Approach to Diversity-Oriented Synthesis of
Aminocyclitols, (−)-Conduramine F-4 and
Polyhydroxyaminoazepanes from a Common Precursor. J. Org.
Chem., 2016, 81, 11574.
(15) Elango S.; Yan, T.-H. A Short Synthesis of (+)-Narciclasine via
a Strategy Derived from Stereocontrolled Epoxide Formation and
SnCl4-Catalyzed Arene-Epoxide Coupling. J. Org. Chem., 2002,
67, 6954.
(16) Lo, H.-J.; Chang, Y.-K.; Yan, T.-H. Chiral Pool Based Efficient
Synthesis of the Aminocyclitol Core and Furanoside of (−)-
Hygromycin A: Formal Total Synthesis of (−)-Hygromycin A. Org.
Lett., 2012, 14, 5896.
(17) (a) Carless, H. A. J.; Oak, O. Z. Total synthesis of (−)-laminitol
(1D-4C-methyl-myo-inositol) via microbial oxidation of toluene.
Tetrahedron Lett., 1991, 32, 1671. (b) Ken-ichi, S.; Masayuki B.;
Makoto, T. Syntheses of Optically Active 2,3,6-Tri-O-benzyl-D-
myo-inositol, Laminitol, and Mytilitol from D-Glucose. Bull.
Chem. Soc. Jpn., 1994, 67, 1633. (c) Sarmah, M. P.; Shashidhar, M.
S.; Sureshan, K. M.; Gonnade, R. G.; Bhadbhade, M. M. Sulfonate
protecting groups. Synthesis of O- and C-methylated inositols: D-
and L-ononitol, D- and L-laminitol, mytilitol and scyllo-inositol
methyl ether. Tetrahedron, 2005, 61, 4437. (d) Angyal, S.; Klavins,
J.; Mills, J. Cyclitols. XXXV. Tridentate complexing of some C-
methyl- and C-hydroxymethyl-cyclitols with borate ions. Aust. J.
Chem., 1974, 27, 1075.
(18) Ananthan, B.; Chang, W.-C.; Lin, J.-S.; Li, P.-H.; Yan, T.-H. A
C2-Symmetric Chiral Pool-Based Flexible Strategy: Synthesis of
(+)- and (−)-Shikimic Acids, (+)- and (−)-4-epi-Shikimic Acids,
and (+)- and (−)-Pinitol. J. Org. Chem., 2014, 79, 2898.
(19) Ackermann, L.; Tom, D. E.; Fürstner, A. Ruthenium Carbene
Complexes with Imidazol-2-ylidene Ligands: Syntheses of
(23) Mitsunobu, O.; Yamada, M. Preparation of Esters of
Carboxylic and Phosphoric Acid via Quaternary Phosphonium
Salts. Bull. Chem. Soc. Jpn., 1967, 40, 2380.
(24) Luche, J. L. Lanthanides in organic chemistry. 1. Selective 1,2
reductions of conjugated ketones. J. Am. Chem. Soc., 1978, 100,
2226.
(25) Pettersson-Fasth, H.; Riesinger, S. W.; Baeckvall, J. E. An
enantioselective route to cis- and trans-2-(hydroxymethyl)-5-
alkylpyrrolidines. J. Org. Chem., 1995, 60, 6091.
(26) (a) Tsuda, T.; Tokai, M.; Ishida T.; Saegusa, T. Palladium-
catalyzed reaction of 1,3-diene monoepoxides with .beta.-keto
acids. Allylic alkylation and isomerization of 1,3-diene
monoepoxides. J. Org. Chem., 1986, 51, 5216. (b) Trost B. M.;
Molander, G. A. Neutral alkylations via palladium(0) catalysis. J.
Am. Chem. Soc., 1981, 103, 5969. (c) Keinan, E.; Roth, Z.
Regioselectivity in organo-transition-metal chemistry. A new
indicator substrate for classification of nucleophiles. J. Org.
Chem., 1983, 48, 1769. (d) Trost B. M.; Angle, S. R. Palladium-
mediated vicinal cleavage of allyl epoxides with retention of
stereochemistry: a cis hydroxylation equivalent. J. Am. Chem. Soc.,
1985, 107, 6123. (e) J. E. Baeckvall, Palladium in some selective
oxidation reactions. Acc. Chem. Res., 1983, 16, 335. (f) Hamasaki,
A.; Maruta, S.; Nakamura, A.; Tokunaga, M. Palladium-Catalyzed
1,4-Addition of Carboxylic Acids to Butadiene Monoxide. Adv.
Synth. Catal., 2012, 354, 2129.
(27) Ogawa, S.; Ohishi, Y.; Asada, M.; Tomoda, A.; Takahashi, A.;
Ooki, Y.; Mori, M.; Itoh M.; Korenaga, T. Convenient synthesis of
(+)-valiolamine and (−)-1-epi-valiolamine from (−)-vibo-quercitol.
Org. Biomol. Chem., 2004, 2, 884.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 14
Insert Table of Contents artwork here
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
14
ACS Paragon Plus Environment