Synthesis of a Cholesterol Side-Chain Triazole Analogue via 'Click' Chemistry

Article abstract of DOI:10.1055/s-0034-1381053

An efficient preparation of a cholesterol analogue possessing a triazole ring is achieved starting from commercially available stigmasterol. The procedure is based on a [3+2] cycloaddition of a cholesterol possessing a side-chain terminal azide with a ter

Full text of DOI:10.1055/s-0034-1381053

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 2826–2830
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I. Seck et al.
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Synthesis
Synthesis of a Cholesterol Side-Chain Triazole Analogue via ‘Click’
Chemistry
Insa Secka
Alioune Fallb
Carmen Lagoc
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Massène Sèneb
Mohamed Gayeb
Matar Seck*a
Generosa Gómezc
Yagamare Fall*c
H
H
OH
H
H
H
H
8 steps
33% overall
HO
HO
a Département de Chimie, Faculté de Medecine, de Pharmacie et
d’Odonto-stomatologie, Université Cheikh Anta Diop, Dakar,
Sénégal
matarsec@yahoo.fr
b Laboratoire de Chimie de Coordination Organique (LCCO),
Département de Chimie, Faculté des Sciences et Techniques,
Université Cheikh Anta Diop de Dakar, Dakar, Sénégal
c Departamento de Química Orgánica, Facultad de Química y
Instituto de Investigación Biomedica (IBI), Universidade de Vigo,
Campus Lagoas de Marcosende, 36310 Vigo, Spain
yagamare@uvigo.es
Received: 30.04.2015
Accepted after revision: 29.06.2015
Published online: 03.08.2015
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DOI: 10.1055/s-0034-1381053; Art ID: ss-2015-c0282-st
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H
Abstract An efficient preparation of a cholesterol analogue possessing
a triazole ring is achieved starting from commercially available stigmas-
terol. The procedure is based on a [3+2] cycloaddition of a cholesterol
possessing a side-chain terminal azide with a terminal acetylene.
OH
H
H
H
H
HO
HO
1
2
Key words triazoles, ‘click’ chemistry, steroids, cholesterol, total syn-
thesis
N
N
N
Steroids are an important class of biological signaling
molecules. They can regulate a very large number of biolog-
ical processes and therefore have the potential to be devel-
oped as drugs for the treatment of various types of diseas-
es.1 Due to their rigid framework with different functional
groups around the tetracyclic core, they represent a syn-
thetic challenge to organic chemists. Most steroid-based
drugs are semi-synthetic compounds prepared by introduc-
ing a particular functionality to the core structure of the
steroid. Many azasteroids have proven to be biologically ac-
tive.2 For example, some of them act as 5α-reductase inhib-
itors,3 antifungal agents4 and γ-aminobutyric acid (GABA)
receptor modulators.5 The large number of steroidal nitro-
gen-containing heterocycles found to be potent inhibitors
of CYP17, a key enzyme involved in androgen biosynthesis,6
prompted us to design the synthesis of cholesterol analogue
1 (Figure 1).
H
H
H
H
H
H
HO
AcO
3
4
Figure 1 The structures of the target cholesterol analogue 1 and some
known steroidal CYP17 inhibitors 2–4
We anticipated that the key azide 6 would be easily ob-
tained from relatively inexpensive and readily available
stigmasterol (5). Azide 6 would then undergo a [3+2] cyc-
loaddition7 with terminal acetylene 7 to afford compound
12 containing the desired triazole side chain (Scheme 2).
Accordingly the Δ5-double bond of stigmasterol (5) was
protected via tosylation, affording compound 8, followed by
methanolysis to give the i-steroid ether 9 (71% overall
yield).8 Reductive ozonolysis9 of 9 afforded alcohol 10 (75%
yield). Tosylation of 10 (86%) followed by azide displace-
Our retrosynthetic strategy for cholesterol analogue 1 is
depicted in Scheme 1.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2826–2830

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ment of the C-22 tosylate afforded an 82% yield of the target
azide 6. With azide 6 in hand, the stage was set for the [3+2]
cycloaddition with terminal acetylene 7, which proceeded
uneventfully to afford the triazole 12 in 90% yield. Depro-
tection of the Δ5-double bond of 12 was carried out using a
catalytic amount of p-toluenesulfonic acid in 1,4-dioxane–
water9a,10 to give a 98% yield of the target cholesterol ana-
logue 1.
OH
N
N
N
7
H
+
H
OH
H
H
N3
HO
1
In summary, we have developed a short and efficient
route toward the synthesis of steroidal nitrogen-containing
heterocycles using the ‘click’ chemistry approach. The bio-
logical evaluation of the new cholesterol analogue 1 is cur-
rently underway. The developed strategy might be useful
for the synthesis of a series of new azasteroids, using vari-
ous commercially or easily available tertiary propargyl al-
cohols to carry out the [3+2] cycloaddition step.
H
H
6
OMe
Solvents were purified and dried by standard procedures. Flash chro-
matography was accomplished using Merck 60 silica gel (230–400
mesh). Analytical TLC was performed on plates precoated with silica
gel (Merck 60 F254, 0.25 mm). Melting points were obtained using a
Gallenkamp apparatus and are uncorrected. Optical rotations were
obtained using a Jasco P-2000 polarimeter. IR spectra were obtained
using a Jasco FT/IR-6100 Type A spectrometer. 1H NMR (400 MHz) and
13C NMR (100 MHz) spectra were recorded on a Bruker ARX-400
spectrometer using TMS as the internal standard; chemical shifts (δ)
H
H
H
HO
5
Scheme 1 Retrosynthetic analysis of cholesterol analogue 1
i
ii
iii
H
H
H
H
H
H
H
H
H
5
8
9
HO
TsO
OMe
N3
OH
OTs
H
H
iv
v
H
vi
H
H
H
H
H
H
OH
10
11
6
7
OMe
OMe
OMe
N
N
N
N
N
N
H
H
H
vii
OH
OH
H
H
H
12
HO
1
OMe
Scheme 2 Reagents and conditions: (i) p-TsCl, py, 87%; (ii) py, MeOH, reflux, 82%; (iii) (a) O3, CH2Cl2–MeOH (2:1), –78 °C; (b) NaBH4, MeOH, 0 °C to r.t.,
75% (2 steps); (iv) p-TsCl, py, 0 °C to r.t., 86%; (v) NaN3, DMF, 50 °C, 82%; (vi) 7, CuSO4·5H2O, sodium ascorbate, t-BuOH–H2O (2:1), 90%; (vii) p-TsOH,
1,4-dioxane–H2O (4:1), 80 °C, 98%.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2826–2830

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are quoted in ppm and coupling constants (J) are given in Hz. In re-
porting H NMR data for steroid structures, not all protons are quot-
ed, only those corresponding to the most characteristic ones. Mass
spectrometry (MS and HRMS) was carried out using a Hewlett-Pack-
ard 5988A spectrometer. Electrospray mass spectra (ESI–MS) were re-
corded on a Bruker APEXQe FT-ICR MS.
MS (FAB): m/z (%) = 427 (17) [M + H]+, 426 (38) [M]+, 425 (100) [M –
H]+, 395 (34) [M – MeO]+, 394 (19) [M – MeOH]+, 393 (41), 255 (31),
253 (40).
HRMS (FAB): m/z [M + H]+ calcd for C30H51O: 427.3940; found:
427.3961.
1
(20S)-20-Hydroxymethyl-6β-methoxy-3α,5-cyclo-5α-pregnane
(10)
Stigmasteryl Tosylate (8)
To a solution of stigmasterol (5) (4.13 g, 10 mmol) in pyridine (33 mL)
at r.t. was added p-TsCl (3.81 g, 20 mmol) and the resulting mixture
was stirred for 48 h. After completion of the reaction (TLC), the mix-
ture was poured into a 10% aq solution of KHCO3 (50 mL). The result-
ing precipitate was filtered and washed with H2O to afford tosylate 8.
A solution of i-stigmasterol (9) (0.66 g, 1.56 mmol) in CH2Cl2 (50 mL)
and MeOH (25 mL) at –78 °C was treated with O3 for 5 min. The reac-
tion vessel was purged with Ar and the contents allowed to warm to
0 °C. NaBH4 (0.59 g, 15.6 mmol) was added and the mixture was
stirred for 24 h, before being poured into a 5% aq solution of HCl (50
mL) at 0 °C. Stirring was continued for 5 min after which the product
was extracted with CH2Cl2 (3 × 50 mL). The combined organic phases
were washed with NaHCO3 (80 mL) and brine (100 mL), dried and
concentrated. The residue was chromatographed over silica gel (20%
EtOAc in hexane) to afford alcohol 10.
Yield: 4.9 g (87%); white solid; mp 121–125 °C; Rf = 0.90 (20% EtOAc
in hexane); [α]D23 –42.65 (c 2.7, CHCl3).
IR (NaCl): 2951, 2362, 2340, 1793, 1542, 1334, 1187 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.3 Hz, 2 H, CH-Ph), 7.33 (d,
J = 8.1 Hz, 2 H, CH-Ph), 5.30 (d, J = 5.2 Hz, 1 H, H-6), 5.14 (dd, J = 8.5,
15.2 Hz, 1 H, H-22), 5.01 (dd, J = 8.6, 15.2 Hz, 1 H, H-23), 4.32 (m, 1 H,
H-3), 2.44 (s, 3 H, CH3-Ts), 1.01 (d, J = 6.6 Hz, 6 H, CH3-26, CH3-27),
0.97 (s, 3 H, CH3-19), 0.84 (t, J = 6.1 Hz, 3 H, CH3-29), 0.79 (d, J = 7.0
Hz, 3 H, CH3-21), 0.67 (s, 3 H, CH3-18).
13C NMR (100 MHz, CDCl3): δ = 144.35 (C-Ph), 138.85 (C-Ph), 138.28
(CH-Ph), 138.21 (CH-Ph), 134.71 (C-5), 129.71 (CH-Ph), 129.31 (CH-
Ph), 127.75 and 127.62 (CH-22 and CH-23), 123.48 (CH-6), 82.36 (CH-
3), 56.73 (CH), 55.90 (CH), 51.21 (CH), 49.92 (CH), 42.17 (C), 40.43
(CH), 39.53 (CH2), 38.85 (CH2), 36.87 (CH2), 36.34 (C), 31.85 (CH),
31.82 (CH), 31.73 (CH2), 28.85 (CH2), 28.62 (CH2), 25.37 (CH2), 24.29
(CH2), 21.60 (CH3), 21.18 (CH3), 21.05 (CH3), 20.95 (CH2), 19.12 (CH3),
18.95 (CH3), 12.22 (CH3), 12.00 (CH3).
Yield: 404 mg (75%); colorless oil; Rf = 0.57 (30% EtOAc in hexane);
[α]D23 +33.53 (c 1.2, CHCl3).
IR (NaCl): 3379, 2930, 2866, 1717, 1455, 1373, 1269, 1095, 736 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.62 (dd, J = 3.2, 10.4 Hz, 1 H, H-22),
3.35 (dd, J = 6.9, 10.4 Hz, 1 H, H-22), 3.31 (s, 3 H, CH3O), 2.76 (t, J = 2.6
Hz, 1 H, H-6), 1.04 (d, J = 6.7 Hz, 3 H, CH3-21), 1.01 (s, 3 H, CH3-18),
0.73 (s, 3 H, CH3-19), 0.64 (dd, J = 5.0, 5.0 Hz, 1 H, H-4), 0.42 (dd,
J = 5.0, 8.0 Hz, 1 H, H-4).
13C NMR (100 MHz, CDCl3): δ = 82.36 (CH-6), 67.93 (CH2-22), 56.51
(CH3O), 56.22 (CH), 52.59 (CH), 47.99 (CH), 43.35 (C), 42.84 (C), 40.10
(CH2), 38.74 (CH), 35.23 (C-5), 35.05 (CH2), 33.33 (CH2), 30.48 (CH),
27.76 (CH2), 24.92 (CH2), 24.26 (CH2), 22.73 (CH2), 21.46 (CH-3), 19.25
(CH3), 16.73 (CH3), 13.06 (CH2-4), 12.29 (CH3).
MS (FAB): m/z (%) = 566 (10) [M]+, 565 (14) [M – H]+, 395 (100) [M –
TsO]+, 394 (45) [M – TsOH]+, 255 (44), 253 (14), 161 (15), 159 (25).
MS (EI): m/z (%) = 347 (8) [M + H]+, 346 (32) [M]+, 332 (14) [M + H –
CH3]+, 331 (53) [M – CH3]+, 315 (15) [M – CH3O]+, 314 (54) [M –
CH3OH]+, 299 (10), 292 (20), 291 (100), 255 (9), 213 (10), 105 (23).
HRMS (FAB): m/z [M + H]+ calcd for C36H55O3S: 567.3872; found:
567.3894.
HRMS (EI): m/z [M]+ calcd for C23H38O2: 346.2872; found: 346.2873.
i-Stigmasteryl Methyl Ether (9)
To a solution of stigmasteryl tosylate (8) (1.2 g, 2.08 mmol) in pyri-
dine (0.5 mL, 6.24 mmol) at r.t. was added MeOH (12 mL). The result-
ing mixture was stirred at 75 °C for 8 h, then cooled to r.t. The solvent
was removed in vacuo and the residue was purified by chromatogra-
py over silica gel (2% EtOAc in hexane) to afford i-stigmasteryl methyl
ether 9.
(20S)-6β-Methoxy-20-(p-toluenesulfonoxymethyl)-3α,5-cyclo-5α-
pregnane (11)
To a solution of alcohol 10 (87 mg, 0.25 mmol) in py (1 mL) at 0 °C
was added p-TsCl (191 mg, 1.0 mmol). The mixture was stirred at the
same temperature for 5 min, before leaving the reaction to warm to
r.t. After 5 d, the reaction was quenched by addition to a mixture of
ice and an aq solution of NaHCO3 (10 mL), and then extracted with
EtOAc (3 × 15 mL). The combined organic phases were washed with
10% aq HCl (20 mL), dried and concentrated. The residue was chroma-
tographed over silica gel (10% EtOAc in hexane) to afford tosylate 11.
Yield: 378 mg (82%); colorless oil; Rf = 0.71 (10% EtOAc in hexane);
[α]D23 +10.02 (c 1.3, CHCl3).
IR (NaCl): 2953, 2930, 2867, 1456, 1382, 1098, 970 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 5.10 (dd, J = 8.5, 15.1 Hz, 1 H, H-22),
4.97 (dd, J = 8.6, 15.1 Hz, 1 H, H-23), 3.28 (s, 3 H, CH3O), 2.70 (d, J = 2.5
Hz, 1 H, H-6), 0.98 (s, 3 H, CH3-18), 0.97 (d, J = 6.7 Hz, 3 H, CH3-21),
0.79 (t, J = 6.5 Hz, 3 H, CH3-29), 0.76 (s, 3 H, CH3-19), 0.69 (s, 3 H, CH3-
18), 0.61 (dd, J = 4.5, 4.5 Hz, 1 H, H-4), 0.39 (dd, J = 8.0, 5.0 Hz, 1 H, H-
4).
13C NMR (100 MHz, CDCl3): δ = 138.30 (CH-22), 129.14 (CH-23), 82.31
(CH-6), 56.61 (CH3O), 56.41 (CH), 56.09 (CH), 51.22 (CH), 48.07 (CH),
43.31 (C), 42.58 (C), 40.48 (CH), 40.17 (CH2), 35.17 (C-5), 35.08 (CH2),
33.30 (CH2), 31.83 (CH), 30.41 (CH), 28.94 (CH2), 25.36 (CH2), 24.89
(CH2), 24.20 (CH2), 22.73 (CH2), 21.35 (CH-3), 21.18 (CH3), 21.03
(CH3), 19.20 (CH3), 18.96 (CH3), 13.05 (CH2-4), 12.36 (CH3), 12.19
(CH3).
Yield: 100 mg (86%); white solid; mp 125–127 °C; Rf = 0.86 (50%
EtOAc in hexane); [α]D24 +31.20 (c 1.0, CHCl3).
IR (ATR): 2931, 2867, 1598, 1455, 1359, 1175, 1096, 953, 934, 813,
660, 553 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 8.3 Hz, 2 H, CH-Ph), 7.31 (d,
J = 8.3 Hz, 2 H, CH-Ph), 3.93 (dd, J = 3.1, 9.2 Hz, 1 H, H-22), 3.76 (dd,
J = 6.5, 9.2 Hz, 1 H, H-22), 3.28 (s, 3 H, CH3O), 2.73 (t, J = 2.6 Hz, 1 H, H-
6), 2.42 (s, 3 H, CH3-Ph), 0.98 (s, 3 H, CH3-18), 0.95 (d, J = 6.6 Hz, 3 H,
CH3-21), 0.65 (s, 3 H, CH3-19), 0.61 (dd, J = 5.0, 5.0 Hz, 1 H, H-4), 0.40
(dd, J = 8.0, 5.5 Hz, 1 H, H-4).
13C NMR (100 MHz, CDCl3): δ = 144.54 (C-Ph), 133.15 (C-Ph), 129.73
(CH-Ph), 127.85 (CH-Ph), 82.25 (CH-6), 75.63 (CH2-22), 56.51 (CH3O),
56.05 (CH), 51.89 (CH), 47.87 (CH), 43.31 (C), 42.82 (C), 39.87 (CH2),
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2826–2830

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36.15 (CH), 35.17 (C-5), 35.01 (CH2), 33.31 (CH2), 30.46 (CH), 27.47
(CH2), 24.91 (CH2), 24.10 (CH2), 22.65 (CH2), 21.60 (CH-3), 21.42 (CH3-
Ph), 19.23 (CH3), 16.80 (CH3), 13.06 (CH2-4), 12.16 (CH3-19).
MS (ESI): m/z (%) = 524 (4) [M + H + Na]+, 523 (17) [M + Na]+, 471 (6)
[M + 2 – MeO]+, 470 (29) [M + H – MeO]+, 469 (100) [M – MeO]+, 297
(14), 139 (16), 99 (4).
(20S)-[(1-Methyl-1H-1,2,3-triazol-4-yl)propan-2-ol]-3β,5-preg-
nene (1)
To a solution of alcohol 12 (107 mg, 0.23 mmol) in 1,4-dioxane–H2O
(4:1) was added p-TsOH (4.5 mg, 0.023 mmol). The mixture was
stirred at 80 °C for 3 h and then allowed to warm to r.t. H2O (5 mL)
was added and the product was extracted with CHCl3 (3 × 10 mL). The
combined organic phases were dried and concentrated to afford a res-
idue which was chromatographed over silica gel (CH2Cl2) to give alco-
hol 1.
HRMS (ESI): m/z [M + Na]+ calcd for C30H44NaO4S: 523.2852; found:
523.2856
Yield: 100 mg (98%); white solid; mp 231–233 °C; Rf = 0.74 (10%
MeOH in EtOAc); [α]D23 –8.2 (c 0.74, MeOH).
(20S)-6β-Methoxy-20-(azidomethyl)-3α,5-cyclo-5α-pregnane (6)
A mixture of tosylate 11 (133 mg, 0.36 mmol) and NaN3 (232 mg, 3.57
mmol) in DMF (6 mL) was stirred at 50 °C for 2 h. Next, H2O (5 mL)
was added and the mixture was extracted with EtOAc (3 × 25 mL).
The combined organic phase was washed several times with brine,
dried and concentrated to afford azide 6, which did not require any
further purification.
IR (NaCl): 3381, 2931, 2866, 2223, 2285, 1727, 1666, 1460, 1376,
1179, 1057, 961, 813 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.41 (s, 1 H, CHN), 5.38 (d, J = 5.3 Hz, 1
H, H-6), 4.37 (dd, J = 3.6, 13.6 Hz, 1 H, H-22), 4.04 (dd, J = 9.4, 13.6 Hz,
1 H, H-22), 3.60–3.49 (m, 1 H, H-3), 2.42 (s, 1 H, OH), 2.38–2.21 (m, 2
H), 2.10–1.94 (m, 4 H), 1.86 (d, J = 9.8 Hz, 2 H), 1.67 [s, 6 H,
(CH3)2COH], 1.58–1.45 (m, 6 H), 1.31–1.05 (m, 6 H), 1.03 (s, 3 H, CH3-
18), 1.01–0.91 (m, 2 H), 0.89 (d, J = 6.6 Hz, 3 H, H-21), 0.76 (s, 3 H,
CH3-19).
13C NMR (100 MHz, CDCl3): δ = 155.36 (NC=CH), 140.79 (C-5), 121.52
(CH-6), 119.55 (CH–N), 71.74 (CH-3), 68.58 (C–OH), 56.45 (CH-14),
56.00 (CH2-22), 53.73 (CH-17), 49.97 (CH), 42.69 (C-13), 42.26 (CH2),
39.51 (CH2), 38.03 (CH), 37.22 (CH2), 36.48 (C-10), 31.87 (CH), 31.83
(CH2), 31.62 (CH2), 30.52 [(CH3)2COH], 28.15 (CH2), 24.39 (CH2), 21.01
(CH2), 19.40 (CH3), 17.12 (CH3), 11.95 (CH3).
Yield: 109 mg (82%); colorless oil; Rf = 0.75 (30% EtOAc in hexane);
[α]D22 +33.72 (c 3.8, MeOH).
IR (NaCl): 2932, 2867, 2094, 1456, 1381, 1269, 1098 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 3.48–3.20 (m, 4 H, H-22, CH3O), 3.15–
3.01 (m, 1 H, H-22), 2.85–2.75 (m, 1 H, H-6), 1.07 (d, J = 6.6 Hz, 3 H,
CH3-21), 1.04 (s, 3 H, CH3-18), 0.96–0.77 (m, 4 H), 0.75 (s, 3 H, CH3-
19), 0.60–0.65 (m, 1 H, H-4), 0.45 (dd, J = 8.0, 5.5 Hz, 1 H, H-4).
13C NMR (100 MHz, CDCl3): δ = 82.35 (CH-6), 58.05 (CH2-22), 56.59
(CH3O), 56.25 (CH), 53.34 (CH), 47.94 (CH), 43.38 (C), 42.95 (C), 40.04
(CH2), 36.94 (CH), 35.23 (C-5), 35.07 (CH2), 33.36 (CH2), 30.52 (CH),
27.99 (CH2), 24.96 (CH2), 24.22 (CH2), 22.74 (CH2), 21.47 (CH-3), 19.29
(CH3), 17.78 (CH3), 13.10 (CH2-4), 12.32 (CH3).
MS (ESI): m/z (%) = 443 (27) [M + 2]+, 442 (100) [M + H]+, 424 (9), 281
(6).
HRMS (ESI): m/z [M + H]+ calcd for C27H44N3O2: 442.3428; found:
442.3424.
HRMS (EI): m/z [M + Na]+ calcd for C23H37N3NaO: 394.28288; found:
394.28293.
(20S)-6β-Methoxy-20-[(1-methyl-1H-1,2,3-triazol-4-yl)propan-2-
ol]-3α,5-cyclo-5α-pregnane (12)
Acknowledgment
To a solution of azide 6 (108 mg, 0.29 mmol) in a mixture of t-BuOH–
H2O (2:1, 3 mL) at r.t. was added CuSO4·5H2O (3.6 mg, 0.014 mmol)
followed by a solution of sodium ascorbate (0.043 mL, 1 M, 0.043
mmol). Alkyne 7 (0.031 mL, 0.32 mmol) was added and the mixture
was stirred for 2 h. Next, H2O (6 mL) was added and the product was
extracted with CH2Cl2 (3 × 10 mL). The combined organic phases were
dried and concentrated to afford a residue which was chromato-
graphed over silica gel (20% EtOAc in hexane) to give alcohol 12.
This work was supported financially by the Xunta de Galicia (project
CN 2012/184). The work of the NMR, SC-XRD and MS divisions of the
research support services of the University of Vigo (CACTI) is also
gratefully acknowledged. A.F., M.S., M.G. and M.S. thank the Universi-
ty Cheikh Anta Diop (Dakar) for financial support for a research stay
at the University of Vigo. I.S. and M.S. thank the Senegalese Ministry
of Scientific Research: FIRST (Fonds d’Impulsion de la Recherche Sci-
entifique et Technique) for a research grant.
Yield: 118 mg (90%); colorless oil; Rf = 0.28 (50% EtOAc in hexane);
[α]D23 +48.48 (c 1, CHCl3).
Supporting Information
IR (NaCl): 3394, 2931, 2867, 2159, 2029, 1976, 1739, 1541, 1457,
1374, 1325 cm–1
.
Supporting information for this article is available online at
1H NMR (400 MHz, CDCl3): δ = 7.40 (s, 1 H, CHN), 4.34 (dd, J = 3.6,
13.6 Hz, 1 H, H-22), 4.01 (dd, J = 9.5, 13.6 Hz, 1 H, H-1), 3.33 (s, 3 H,
CH3O), 2.78 (t, J = 2.7 Hz, 1 H, H-6), 1.64 [s, 6 H, (CH3)2COH], 0.98 (s, 3
H, CH3-18), 0.75 (s, 3 H, CH3-19), 0.70–0.65 (m, 1 H, H-4), 0.44 (dd,
J = 8.0, 5.5 Hz, 1 H, H-4).
13C NMR (100 MHz, CDCl3): δ = 155.41 (C=CH), 119.62 (CH–N), 82.29
(CH-6), 68.36 (C–OH), 56.58 (CH3O), 56.19 (CH), 56.00 (CH2-22), 53.88
(CH), 47.88 (CH), 43.35 (C), 43.12 (C), 39.99 (CH2), 38.01 (CH), 35.16
(C-5), 35.06 (CH2), 33.34 (CH2), 30.49 (CH), 30.44 (CH3COH), 28.21
(CH2), 24.93 (CH2), 24.26 (CH2), 22.69 (CH2), 21.43 (CH-3), 19.26 (CH3-
18), 17.06 (CH3-19), 13.10 (CH2-4), 12.33 (CH3-21).
http://dx.doi.org/10.1055/s-0034-1381053.
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References
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456.35816.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2826–2830

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Special Topic
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