Synthesis of 1-deoxyeldecalcitol, a biologically interesting analog of 1α,25-dihydroxy-2β-(3-hydroxypropoxy) vitamin D3 (eldecalcitol)

Article abstract of DOI:10.3987/COM-11-12189

A synthesis of biologically interesting 1-deoxyeldecalcitol, a dehydroxylated analog at the 1?-position of 1α,25-dihydroxy-2β-(3- hydroxypropoxy) vitamin D₃ (eldecalcitol), using Trost's coupling methodology is described.

Full text of DOI:10.3987/COM-11-12189

HETEROCYCLES, Vol. 83, No. 6, 2011
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HETEROCYCLES, Vol. 83, No. 6, 2011, pp. 1385 - 1394. © The Japan Institute of Heterocyclic Chemistry
Received, 25th February, 2011, Accepted, 30th March, 2011, Published online, 13th April, 2011
DOI: 10.3987/COM-11-12189
SYNTHESIS OF 1-DEOXYELDECALCITOL, A BIOLOGICALLY
INTERESTING ANALOG OF 1,25-DIHYDROXY-2-(3-HYDROXY-
PROPOXY)VITAMIN D3 (ELDECALCITOL)*1
Hirotaka Sasaki,a Kohei Eto,a Keisuke Takahashi,a Jun Ishihara,a Susumi
Hatakeyama,a and Noboru Kubodera*b
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki
852-8521, Japana and Chugai Pharmaceutical Co., Ltd., 2-1-1,
Nihonbashi-Muromachi, Chuo-ku, Tokyo 103-8324, Japanb
Abstract – A synthesis of biologically interesting 1-deoxyeldecalcitol, a
dehydroxylated analog at the 1-position of 1,25-dihydroxy-2-(3-hydroxy-
propoxy)vitamin D3 (eldecalcitol), using Trost’s coupling methodology is
described.
It is well-established that vitamin D3 (cholecalciferol 1) ingested into foods or synthesized in the skin is
metabolized to 25-hydroxyvitamin D3 (calcifediol 2) in the liver, which is further hydroxylated at the
1-position in the kidney to produce the active form, 1,25-dihydroxyvitamin D3 (calcitriol 3).2
Calcitriol (3) is well recognized as a potent regulator of calcium and phosphorous metabolism while also
possessing regulatory effects on cell proliferation and differentiation processes.3 In Japan, calcitriol (3)
and its synthetic prodrug, 1-hydroxyvitamin D3 (alfacalcidol 4), which is also activated to 3 in the body
(liver and bone), have been widely used for the treatment of osteoporosis for more than a
quarter-century.4 Calcitriol (3) and alfacalcidol (4) have been recognized as very safe medicines that
show mild or moderate increase in bone mineral density (BMD) in osteoporotic patients. There exists
intense interest in obtaining active vitamin D3 analogs more potent than 3 and 4 in increasing BMD and
preventing bone fracture with less calcemic activity for treating osteoporosis. 1,25-Dihydroxy-2-
(3-hydroxypropoxy)vitamin D3 (eldecalcitol 5, developing code; ED-71), which possesses a
hydroxypropoxy substituent at the 2-position of the A-ring of 3, is such an analog that shows potent
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*This paper is dedicated to the memory of the late Dr. Etsuro Ogata, Professor Emeritus, Tokyo
University/Director Emeritus, Cancer Institute Hospital Japan, who passed away on November 1, 2009.

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HETEROCYCLES, Vol. 83, No. 6, 2011
effects on bone therapy.5-7 Recent completion of a phase III clinical trial of 5 for bone fracture
prevention and increase in BMD in comparison with alfacalcidol (4) produced excellent results.8,9
Eldecalcitol (5) is now ready for marketing as an excellent medicine for the treatment of osteoporosis in
Japan (Scheme 1).
25
OH
OH
25
1
1
liver
kidney
HO
HO
HO
OH
calcifediol (2)
cholecalciferol (1)
calcitriol (3)
liver/bone
OH
OH
1
1
1
1
HO
OH
HO
2
HO
OH
1
O
OH
O
OH
eldecalcitol (5)
1-deoxyeldecalcitol (6)
alfacalcidol (4)
Scheme 1. Activation of cholecalciferol (1) and alfacalcidol (4) to calcitriol (3) and structures of
eldecalcitol (5) and 1-deoxyeldecalcitol (6)
Figure 1 illustrates the basic relationship between serum calcium level (calcemic activity) and the
targeted effect on bone (BMD increase) with cholecalciferol (1), calcitriol (3)/alfacalcidol (4), and
eldecalcitol (5).10 The potent effect on bone is highest with 5 followed by 3 and 4 and then 1, at doses
that induce approximately the same level of serum calcium (Figure 1). The question is what the
different mode-of-action between calcitriol (3)/alfacalcidol (4) and eldecalcitol (5) is. Although
specific physiological properties and mechanism of action of 5 are constantly being investigated, the
long duration of 5 in the blood stream arises from its strong affinity for vitamin D binding protein (DBP)
and might explain, in part, the enhanced activity of 5 over 3 and 4 toward bone.11,12 Interestingly, an
idea was presented recently that calcitriol (3) is responsible for calcemic activity whereas the strong

HETEROCYCLES, Vol. 83, No. 6, 2011
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binding of calcifediol (2) to DBP and the long existence of 2 in blood are responsible for an anabolic
effect on bone such as BMD increase.13 Since the structural relationship between 3 and 2 corresponds
to that between eldecalcitol (5) and 25-hydroxy-2-(3-hydroxypropoxy)vitamin D3 (1-deoxyeldecalcitol
6), we have been very interested in the biological actions of 6, e.g. possible hydroxylation of 6 to 5 in
the kidney, affinity for DBP, duration in blood stream, and anabolic effect on bone (Scheme 1).
Therefore, in this paper we describe the synthesis of 1-deoxyeldecalcitol (6) to explore
structure-biological activity relationships between medicinally important eldecalcitol (5) and related
analogs including 6.11,14-18
Figure 1. Basic relationship between calcemic activity (serum calcium) and effect on bone (BMD
increase) with cholecalciferol (1), calcitriol (3)/alfacalcidol (4), and eldecalcitol (5)
The synthesis of 1-deoxyeldecalcitol (6) was envisioned using Trost’s methodology involving
palladium-catalyzed coupling between A-ring fragment 15 and C/D-ring fragment 16 (Scheme 2).19,20
The synthesis of A-ring fragment 15 started from epimeric alcohol 821 which was developed in our
previous synthesis of eldecalcitol analogs from C2-symmetrical epoxide 7.22 Thus, alcohol 8 was
acetylated to acetate 9, which was treated with tetrakis(triphenylphosphine)palladium (0) [(PPh3)4Pd]
and ammonium formate (HCO2NH4) to give deacetoxy product 10 in 91% yield from 8.23 Diol 11 was
obtained in 94% yield after deprotection of the acetonide moiety in 10 using 60% acetic acid.
Mitsunobu reaction24 of 11 with diethyl azodicarboxylate (DEAD) and triphenylphosphine (PPh3) in
1,4-dioxane afforded epoxide 12 in 71% yield as a sole product. Reaction of 12 with lithium
trimethylsilylacetylide in the presence of boron trifluoride diethyl etherate (BF3-OEt2) at -78 °C gave the

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HETEROCYCLES, Vol. 83, No. 6, 2011
enyne 13 in 86% yield, which was then converted to A-ring fragment 15 by saponification with 3 M
sodium hydroxide (NaOH) and subsequent protection of the hydroxyl groups as their triethylsilyl (TES)
ether in 93% overall yield.
With A-ring fragment 15 in hands, we next coupled it to C/D-ring fragment 16 using Trost’s
methodology.19,20 Thus, A-ring fragment 15 was coupled with C/D-ring fragment 16, which was
readily secured by our method25 from commercially available calcifediol (2), in the presence of
(PPh3)4Pd and triethylamine (Et3N) in boiling toluene to produce the desired coupling product 17,
although the coupling reaction conditions were not optimized. Desilylation of 17 with 47%
hydrofluoric acid (HF) in acetonitrile (MeCN) at room temperature gave rise to 1-deoxyeldecalcitol (6)
in 10% yield from 15 (Scheme 2).
O
O
O
O
O
Ref. 21
BnO
OBn
a) 100%
OPiv
b) 91%
OPiv
TMS
OH
OAc
C -symmetrical epoxide (7)
2
O
O
(8)
(9)
O
HO
HO
c) 94%
d) 71%
OPiv
e) 86%
f) 99%
OPiv
O
O
HO
O
OPiv
O
O
OPiv
O
(10)
(11)
(13)
(12)
OH
OH
H
H
Br
OTES
g) 93%
C/D-ring fragment (16)
i)
HO
(6) 10% (2 steps)
TESO
h)
O
OH
O
TESO
(14)
A-ring fragment (15)
O
OTES
(17)
Scheme 2. Synthesis of 1-deoxyeldecalcitol (6). Reagents and conditions: a) Ac2O/pyridine/DMAP/
CH2Cl2, rt. b) (PPh3)4Pd/HCO2NH4/Et3N/THF, reflux. c) 60% aqueous AcOH, rt. d) PPh3/DEAD/
1,4-dioxane, reflux. e) HC CTMS/n-BuLi/BF3-OEt2/THF, -78 °C to rt. f) 3 M NaOH/MeOH, rt. g)
TESOTf/2,6-lutidine/CH2Cl2, -40 °C. h) (PPh3)4Pd/Et3N/toluene, reflux. i) 47% aqueous HF/MeCN,
0 °C.
Based on the Trost’s coupling methodology involving A-ring fragment 15 and C/D-ring fragment 16, we
completed the synthesis of 1-deoxyeldecalcitol (6). The detailed biological actions of 6 in comparison

HETEROCYCLES, Vol. 83, No. 6, 2011
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with eldecalcitol (5) and related analogs will be investigated and reported in due course.
EXPERIMENTAL
Anhydrous THF was purchased from Kanto Chemical Co., Inc. MeOH and EtOH were distilled from
sodium, toluene was distilled from phosphorus pentoxide, and CH2Cl2, Et3N, DMF, and pyridine were
distilled from calcium hydride. All other purchased solvents and reagents were used without further
purification. All reactions were carried out under an atmosphere of argon unless otherwise noted.
Celite 545 was purchased from Nacarai Tesque Inc. All extracts were dried over magnesium sulfate
and evaporated under reduced pressure with a rotary evaporator. Chromatographic purification was
carried out with Silica Gel 60N Cat. No. 37560-84 purchased from Kanto Chemical Co., Inc., and flash
column chromatography with Silica Gel 60N Cat. No. 37563-84 from Kanto Chemical Co., Inc.
13
Optical rotations were measured with JASCO DIP-370 polarimeter. 1H and C NMR spectra were
recorded on VARIAN Gemini-300 and Gemini-400 spectrometers using CDCl3 as a solvent. Chemical
shifts are reported in parts per million (ppm) calibrated from CHCl3 (7.26 ppm) or tetramethylsilane
1
13
(0.00 ppm) for H NMR and CDCl3 (77.1 ppm) for C NMR. Infrared (FTIR) spectra were obtained
using JASCO FT/IR-5300, JEOL JIR-6000, and Hitachi 270-30 spectrophotometers. Mass spectra
(MS) were measured with JEOL JMS-DX303 instrument. High resolution mass spectra (HRMS) were
recorded on JEOL JMS-AX-500 and VG Auto Spec Q instruments.
3-((S)-1-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)but-3-enyloxy)propyl Pivalate (10): To a stirred
solution of 8 (450 mg, 1.36 mmol), pyridine (0.26 mL, 3.26 mmol), and DMAP (1.6 mg, 0.013 mmol) in
CH2Cl2 (4 mL) at rt, was added Ac2O (0.19 mL, 1.96 mmol). The resulting mixture was stirred at rt,
diluted with Et2O, washed with 1 M HCl, saturated NaHCO3, and saturated NaCl, evaporated, and
chromatographed on silica gel short column. Elution with n-hexane-AcOEt (12:1) gave 9 (510 mg,
100%), which was used for the next reaction without further purification. 1H NMR (CDCl3):  1.20
(9H, s), 1.33 (3H, s), 1.42 (3H, s), 1.88 (2H, quint, J = 6.1 Hz), 2.09 (1.5H, s), 2.11 (1.5H, s), 3.52-4.16
(8H, m), 5.24-5.34 (2.5H, m), 5.54 (0.5H, d, J = 5.6 Hz), 5.80-5.89 (1H, m). To a stirred and degassed
solution of 9 (0.3 g, 0.81 mmol) and Et3N (0.6 mL, 4.3 mmol) in THF (8 mL), were added HCO2NH4
(0.5 g, 7.93 mmol) and (PPh3)4Pd (2.7 mg, 0.023 mmol). The resulting mixture was refluxed for 2 h.
To the mixture, was added additional (PPh3)4Pd (2.7 mg, 0.023 mmol). The resulting mixture was
refluxed for 40 min, diluted with AcOEt, washed with saturated NaCl, evaporated, and chromatographed
27
on silica gel. Elution with n-hexane-AcOEt (9:1) gave 10 (227 mg, 91%) as a colorless oil. []D

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HETEROCYCLES, Vol. 83, No. 6, 2011
+20.8° (c 1.00, CHCl3). FTIR (neat):  1729, 1472, 1374, 1281, 1216, 1158, 1071 cm-1. 1H NMR
(CDCl3):  1.25 (9H, s), 1.41 (3H, s), 1.43 (3H, s), 1.87 (2H, quint, J = 6.4 Hz), 2.25-2.37 (2H, m),
3.38-3.40 (1H, m), 3.57-3.68 (2H, m), 3.87 (1H, m), 4.03 (2H, q, J = 4.6 Hz), 4.15 (2H, t, J = 6.4 Hz),
5.06-5.14 (2H, m), 5.84 (1H, dt, J = 7.1, 10.0 Hz). 13C NMR (CDCl3):  25.3, 26.6, 27.1, 29.3, 35.5,
38.7, 61.2, 66.2, 66.8, 76.7, 79.6, 109.0, 117.4, 134.1, 178.4. EIMS m/z 314 (M+), 143 (100%).
HRMS (EI) calcd for C17H36O5 (M+) 314.2093, found 314.2080.
3-((2R,3S)-1,2-Dihydroxyhex-5-en-3-yloxy)propyl Pivalate (11): A solution of 10 (380 mg, 1.21
mmol) in 60% AcOH (15 mL) was stirred at rt for 8 h, basified with saturated NaHCO3, extracted with
CH2Cl2, washed with saturated NaCl, evaporated, and chromatographed on silica gel. Elution with
28
n-hexane-AcOEt (3:2 then 1:1) gave 11 (311 mg, 94%) as a colorless oil. []D +19.1° (c 1.00,
CHCl3). FTIR (neat):  3437, 1725, 1287, 1166, 1107 cm-1. 1H NMR (CDCl3):  1.20 (9H, s), 1.88
(2H, quint, J = 6.1 Hz), 2.30-2.40 (3H, m), 2.79 (1H, m), 3.46-3.50 (2H, m), 3.66-3.78 (4H, m), 4.10
(1H, quint, J = 6.1 Hz), 4.27 (1H, quint, J = 6.1 Hz), 5.08-5.16 (2H, m), 5.78-5.88 (1H, m). 13C NMR
(CDCl3):  27.1, 29.3, 34.7, 61.1, 63.2, 66.4, 72.3, 80.5, 117.4, 134.2, 178.7. EIMS m/z 274 (M+), 143
(100%). HRMS (EI) calcd for C14H26O5 (M+) 274.1780, found 274.1762.
3-((S)-1-((R)-Oxiran-2-yl)but-3-enyloxy)propyl Pivalate (12): To a stirred solution of 11 (311 mg,
1.13 mmol) in 1,4-dioxane (11 mL) at rt, were added PPh3 (0.86 g, 3.4 mmol) and DEAD (40% in
toluene, 1.56 mL, 5.16 mmol). The resulting mixture was refluxed for 24 h, cooled to rt, evaporated,
and chromatographed on silica gel. Elution with n-hexane-AcOEt (10:1) gave 12 (206 mg, 71%) as a
26
colorless oil. []D +7.61° (c 1.00, CHCl3). IR (neat):  1724, 1476, 1284, 1161 cm-1. 1H NMR
(CDCl3):  1.20 (9H, s), 1.86 (2H, quint, J = 6.3 Hz), 2.30-2.44 (2H, m), 2.73-2.80 (2H, m), 2.94-2.96
(1H, m), 3.18-3.23 (1H, m), 3.46-3.52 (1H, m), 3.64-3.68 (1H, m), 4.14 (2H, t, J = 6.3 Hz), 5.07-5.16
(2H, m), 5.82-5.92 (1H, dt, J = 7.1, 10.3 Hz). 13C NMR (CDCl3):  27.1, 29.3, 37.0, 38.7, 45.3, 53.0,
61.2, 66.6, 78.4, 117.3, 133.9, 178.4. EIMS m/z 256 (M+), 143 (100%). HRMS (EI) calcd for
C14H24O4 (M+) 256.1675, found 256.1672.
3-((4S,5R)-5-Hydroxy-8-(trimethylsilyl)oct-1-en-7-yn-4-yloxy)propyl Pivalate (13): To a stirred
solution of trimethylsilylacetylene (423 l, 2.99 mmol) in THF (8 mL) at -78 °C, was added n-BuLi
(2.66 M solution in n-hexane, 1.0 mL, 2.66 mmol) and stirring was continued at -78 °C for 4 h. To the
stirred mixture at -78 °C, were added 12 (150 mg, 0.586 mmol) in THF (8 mL) and BF3-OEt2 (384 L,

HETEROCYCLES, Vol. 83, No. 6, 2011
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0.434 mmol). The resulting mixture was allowed to warm to rt, stirred at rt for 14 h, quenched with
saturated NaHCO3 (1.0 mL), extracted with CH2Cl2, washed with saturated NaCl, evaporated, and
chromatographed on silica gel. Elution with n-hexane-AcOEt (20:1) gave 13 (178 mg, 86%) as a
28
colorless oil. []D +17.0° (c 1.00, CHCl3). FTIR (neat):  3500, 1728, 1477, 1402, 1286, 1252,
1162, 1106 cm-1. 1H NMR (CDCl3):  0.15 (9H, s), 1.19 (9H, s), 1.87 (2H, quint, J = 6.1 Hz),
2.32-2.35 (2H, m), 2.51 (2H, d, J = 6.1 Hz), 3.37 (1H, q, J = 5.6 Hz), 3.52-3.63 (2H, m), 3.76 (1H, q, J =
5.6 Hz), 4.09-4.20 (2H, m), 5.05-5.14 (2H, m), 5.80-5.89 (1H, m). 13C NMR (CDCl3):  0.00, 24.3,
27.2, 29.3, 34.1, 38.7, 61.2, 66.4, 70.4, 80.9, 87.5, 103.0, 117.2, 134.6, 178.5. EIMS m/z 354 (M+), 57
(100%). HRMS (EI) calcd for C19H34O4Si (M+) 354.2227, found 354.2224.
(4R,5S)-5-(3-Hydroxypropoxy)oct-7-en-1-yn-4-ol (14): To a stirred solution of 13 (77.5 mg, 0.219
mmol) in MeOH (2 mL) at 0 °C, was added 3 M NaOH (1 mL). The resulting mixture was stirred at rt
for 8 h, neutralized with 1 M HCl (0.5 mL), evaporated, and chromatographed on silica gel. Elution
with n-hexane-AcOEt (20:1) gave 14 (43.1 mg, 99%) as a colorless oil. []D28 +23.5° (c 1.00, CHCl3).
FTIR (neat):  3296, 1641, 1423, 1004 cm-1. 1H NMR (CDCl3):  1.81 (2H, quint, J = 2.7 Hz), 2.06
(1H, s), 2.34-2.38 (2H, m), 2.51 (3H, m), 3.43-3.46 (1H, m), 3.73-3.80 (5H, m), 5.10-5.17 (2H, m),
5.83-5.90 (1H, m). 13C NMR (CDCl3):  22.9, 32.5, 34.6, 61.1, 69.1, 70.7, 70.9, 81.2, 81.4, 117.7,
134.7. EIMS m/z 198 (M+), 59 (100%). HRMS (EI) calcd for C11H18O3 (M+) 198.1256, found
198.1242.
(4S,5R)-4-(3-(Trimethylsilyloxy)propoxy)-5-(trimethylsilyloxy)oct-1-en-7-yne (15): To a stirred
mixture of 14 (50 mg, 0.252 mmol) in CH2Cl2 (2 mL) at -40 °C, were added 2,6-lutidine (283 L, 1.26
mmol) and TESOTf (240 L, 1.26 mmol). The resulting mixture was stirred at the same temperature
for 9 h, quenched with saturated NaHCO3 (2 mL), extracted with CH2Cl2, washed with saturated
NaHCO3 and saturated NaCl, evaporated, and chromatographed on silica gel. Elution with
24
n-hexane-CH2Cl2 (6:1) containing 2% Et3N gave 15 (100 mg, 93%) as a colorless oil. []D -3.7° (c
1.06, CHCl3). FTIR (neat):  1463, 1416, 1238, 1100, 1010 cm-1. 1H NMR (CDCl3):  0.60 (12H, q,
J = 8.1 Hz), 0.93 (18H, t, J = 8.1 Hz), 1.77 (2H, quint, J = 6.4 Hz), 1.97 (1H, s), 2.27-2.47 (4H, m), 3.38
(1H, q, J = 5.1 Hz), 3.61 (2H, q, J = 6.3 Hz), 3.68 (2H, t, J = 6.3 Hz), 3.78 (1H, q, J = 5.1 Hz), 5.03-5.12
(2H, m), 5.82-5.93 (1H, m). 13C NMR (CDCl3):  4.4, 5.0, 6.7, 6.8, 23.8, 33.4, 34.8, 59.9, 67.4, 70.0,
72.2, 81.3, 81.6, 116.6, 135.3. EIMS m/z 426 (M+), 115 (100%). HRMS (EI) calcd for C23H46O3Si2
(M+) 426.2986, found 426.2997.

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HETEROCYCLES, Vol. 83, No. 6, 2011
(1R,2S,5Z)-2-(3-Hydroxypropoxy)-5-((E)-2-((1R,3aS,7aR)-hexahydro-1-((R)-6-hydroxy-6-methylhe
ptan-2-yl)-7a-methyl-1H-inden-4(7aH)-ylidene)ethylidene-4-methylenecyclohexanol (6): To
stirred and degassed solution of 15 (90 mg, 0.211 mmol), 16 (90 mg, 0.253 mmol), and Et3N (4.7 mL) in
toluene (3.2 mL) at rt, was added (PPh3)4Pd (20 mg, 0.017 mmol). The resulting mixture was refluxed
for 22 h, diluted with Et2O, and filtrated with Celite. The filtrate was diluted with AcOEt, washed with
a
H2O and saturated NaCl, evaporated, and chromatographed on silica gel.
Elution with
n-hexane-AcOEt (20:1) containing 2% Et3N gave crude 17 (64 mg), which was used for the next
reaction without further purification. To a stirred mixture of crude 17 (64 mg) in MeCN (16 mL) at
0 °C, was added 47% HF (100 L). The resulting mixture was stirred at the same temperature for 10
min, neutralized with NaHCO3 (3 g), extracted with Et2O, washed with saturated NaCl, evaporated, and
20
chromatographed on silica gel. Elution with AcOEt gave 6 (10.2 mg, 10%) as a white solid. []D
+19.9° (c 0.32, CHCl3). FTIR (neat):  3387, 2942, 1710, 1374, 1081 cm-1. 1H NMR (CDCl3):  0.54
(3H, s), 0.93 (3H, d, J = 6.6 Hz), 1.03-1.06 (1H, m), 1.25 (3H, s), 1.27-1.35 (4H, m), 1.41-1.54 (10H, m),
1.65-1.67 (2H, m), 1.83-1.87 (2H, m), 1.95-2.05 (2H, m), 2.26 (1H, br s), 2.37 (2H, m), 2.49-2.57 (2H,
m), 2.81 (1H, m), 3.58 (1H, quint, J = 4.2 Hz), 3.68-3.79 (5H, m), 4.01 (1H, br s), 4.92 (1H, s), 5.11 (1H,
s), 6.02 (1H, d, J = 11.5 Hz), 6.26 (1H, d, J = 11.5 Hz). 13C NMR (CDCl3):  12.0, 18.8, 20.8, 22.3,
23.6, 27.7, 29.0, 29.2, 29.3, 32.2, 36.1, 36.4, 40.5, 41.0, 44.4, 45.8, 56.3, 56.5, 61.6, 67.2, 68.9, 71.1,
79.2, 114.7, 117.5, 122.9, 133.6, 141.6, 142.6. EIMS m/z 474 (M+), 134 (100%). HRMS (EI) calcd
for C30H50O4 (M+) 474.3709, found 474.3710.
ACKNOWLEDGMENTS
We are grateful to Professor David Horne of Division of Molecular Medicine, City of Hope for reading
of the manuscript and helpful suggestions.
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