Preparation of androstanes related to aphidicolin

Article abstract of DOI:10.1135/cccc20071545

The preparation of 3α,4α,17β-trihydroxy-, 3α,4α,16α,17α- and 2α,3α,16α, 17α-tetrahydroxy-5α-androstane derivatives (5, 11, 18) from testosterone as steroidal analogues of diterpenoid inhibitor of DNA polymerase a, aphidicolin, is described. The crystal structure of 5α-androstane- 3α,4α,17β-triyl triacetate (6) is reported.

Full text of DOI:10.1135/cccc20071545

Preparation of Androstanes Related to Aphidicolin
1545
PREPARATION OF ANDROSTANES RELATED TO APHIDICOLIN
a,
b
c
d1
Cavit UYANIK *, Kudret YILDIRIM , Aslihan MALAY , James R. HANSON and
d2
Peter B. HITCHCOCK
a
Department of Chemistry, University of Kocaeli, Izmit, 41380, Kocaeli, Turkey;
e-mail: cuyanik@kou.edu.tr
Department of Chemistry, University of Sakarya, Adapazari, 54187, Sakarya, Turkey;
b
e-mail: kudrety@sakarya.edu.tr
Department of Chemistry, Gebze Institute of Technology, Gebze, 41400, Kocaeli, Turkey;
c
e-mail: amalay@gyte.edu.tr
d
Department of Chemistry, University of Sussex, Brighton, Sussex, BN1 9QJ, U.K.;
1
2
e-mail: j.r.hanson@sussex.ac.uk, p.b.hitcock@sussex.ac.uk
Received July 25, 2007
Accepted Novem ber 9, 2007
Th e preparation of 3α,4α,17β-trih ydroxy-, 3α,4α,16α,17α- an d 2α,3α,16α,17α-tetrah ydroxy-
5α-an drostan e derivatives (5, 11, 18) from testosteron e as steroidal an alogues of diterpen oid
in h ibitor of DNA polym erase α, aph idicolin , is described. Th e crystal structure of
5α-an drostan e-3α,4α,17β-triyl triacetate (6) is reported.
Keyw ord s: Aph idicolin ; Steroids; An drostan es; Diterpen oids; Catalytic h ydroxylation ; X-ray
crystallograph y; DNA polym erase in h ibitors.
Aph idicolin (1) is an in h ibitor of DNA polym erase α (refs1,2). Its glycin ate
ester reach ed clin ical trial as a tum our in h ibitory substan ce. Th e structure-
activity studies wh ich h ave been reported3 on th is relatively expen sive
diterpen oid suggest th at th e activity m ay be related to th e distan ce separat-
in g th e h ydroxyl groups on rin gs A an d D of aph idicolin . Th ere is a form al
sim ilarity between th e structure of aph idicolin an d th e steroids an d, un like
th e m ajority of th e diterpen oids, both belon g to th e sam e en an tiom eric se-
ries. Th e bin din g of th e steroid h orm on es to th e steroid n uclear receptors
results in th e in itiation of n ucleic acid biosyn th esis. Th is in volves DNA
polym erase activity. Con sequen tly, we h ave prepared4–6 a n um ber of ste-
roids with structures th at h ave a sim ilarity to aph idicolin in th e relative dis-
position of th eir h ydroxyl groups. Th e C-3:C-17 an d C-4α (h ydroxym eth yl):
C-17 distan ces in aph idicolin are 8.46 an d 8.84 Å wh ilst in a typical 5α-
steroid C-3:C-17 is 8.70 an d C-4:C-17 8.09 Å. Prelim in ary screen in g results
suggest th at som e of th ese com poun ds possess tum our in h ibitory activity.
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1545–1552
© 2007 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc20071545

1546
Uyanik, Yildirim, Malay, Hanson, Hitchcock:
In th is paper we report th e preparation of 5α-an drostan e-3α,4α,17β-
triol (5), 5α-an drostan e-3α,4α,16α,17α-tetrol (11) an d 5α-an drostan e-
2α,3α,16α,17α-tetrol (18) from th e readily available testosteron e (2). Th ese
com poun ds h ave a 3α-h ydroxyl group typical of aph idicolin .
OH
OH
CH2OH
D
C
H
A
B
HO
O
H
HOH2C
1
2
5α-An drost-3-en -17β-yl acetate7 (3) was obtain ed from testosteron e (2)
by treatm en t with boron trifluoride eth erate-sodium boroh ydride an d
acetic an h ydride. Hydrolysis of th e 17β-acetate gave th e 17β-alcoh ol8 4.
Catalytic osm ylation of 5α-an drost-3-en -17β-ol (4) usin g potassium
h exacyan oferrate(III) as th e co-oxidan t9, gave 5α-an drostan e-3α,4α,17β-
triol (5) (Sch em e 1). Th e 1H NMR spectrum of th e product, determ in ed
in pyridin e-d5 at 500 MHz, con tain ed sign als at δ 3.69 (1 H, dd, J = 3 an d
OR
OR
OsO4
4
71%
RO
H
H
OR
5, R = H
3, R = Ac
4, R = H
Ac2O/Py
6, R = Ac
CrO3
O
NNH2
I
NH2NH2•H2O
I2/NEt3
80.5%
92%
7
8
9
Na/EtOH
83.5%
H
OH
OH
OsO4
61%
10
HO
11
H
H
OH
SCHEME 1
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Preparation of Androstanes Related to Aphidicolin
1547
11 Hz, 4-H) an d δ 4.28 (1 H, q, J = 3 Hz, 3-H). Th e m agn itude of th e cou-
plin g con stan ts was con sisten t with th e presen ce of th e 4α- an d 3α-h ydro-
xyl groups, respectively. Th us th e 4-H reson an ce revealed a diaxial an d an
axial-equatorial couplin g wh ilst th e 3-H reson an ce con tain ed equatorial-
axial an d diequatorial couplin gs. Th e stereoch em istry was con firm ed by an
X-ray crystal structure of th e triacetate 6 as sh own in Fig. 1.
Oxidation of 5α-an drost-3-en -17β-ol (4) with ch rom ium trioxide gave
5α-an drost-3-en -17-on e8 (7) wh ich was con verted to its h ydrazon e 8 with
h ydrazin e h ydrate an d trieth ylam in e. Decom position of th e h ydrazon e
with iodin e an d trieth ylam in e in tetrah ydrofuran 10 gave 17-iodo-
5α-an drosta-3,16-dien e (9). Apart from th e sign als assign ed to th e rin g A
1
double bon d, th e H NMR spectrum of th e product con tain ed a n ew alken e
sign al at δ 6.12. Hydrogen olysis of th e iodin e with sodium in eth an ol af-
ford 5α-an drosta-3,16-dien e (10) wh ich possessed sign als of olefin icproton s
at δ 5.69 an d 5.84 (H-17 an d H-16, respectively) an d at δ 5.26 an d 5.52 (H-4
an d H-3, respectively). Th is m eth od of preparin g th e 16-en es is preferable
over th at of deh ydration of th e 17-alcoh ols wh ich can brin g about rear-
ran gem en t of C-18.
Catalytic osm ylation of dien e 10 gave 5α-an drostan e-3α,4α,16α,17α-
tetrol (11). Th e 1H NMR spectrum determ in ed in pyridin e-d5 at 500 MHz,
con tain ed sign als at δ 3.67 (doublet of doublet, J = 3 an d 11 Hz), δ 3.82
(doublet, J = 5.3 Hz), δ 4.27 (quartet, J = 3 Hz) an d δ 4.67 (quartet, J =
FIG. 1
X-ray structure of 6
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1545–1552

1548
Uyanik, Yildirim, Malay, Hanson, Hitchcock:
5.3 Hz) wh ich were assign ed to H-4, H-17, H-3 an d H-16, respectively.
Irradiation of th e H-18 sign al at δ 0.70 gave n uclear Overh auser effect en -
h an cem en ts of 6.4% to th e H-17 sign al an d 4.4% to th e H-16 sign al, sh ow-
in g th at both th e 16- an d 17-h ydroxyl groups were α-orien ted. Irradiation
of th e H-19 sign al at δ 0.85 gave an NOE en h an cem en t of 4.4% to th e
H-4 sign al at δ 3.67. Th ese en h an cem en ts, togeth er with th e m agn itude
of th e couplin g con stan ts, were con sisten t with th e 5α-an drostan e-
3α,4α,16α,17α-tetrol stereoch em istry of th e com poun d 11.
5α-An drostan e-2α,3α,16α,17α-tetrol (18) was prepared by a sim ilar route
(Sch em e 2) from 3β-h ydroxyan drost-5-en -17-on e (12). 5α-An drost-2-en -
17-on e11 (14) was obtain ed by elim in ation of th e 3β-tosylate 13 with
collidin e an d con verted in to 5α-an drosta-2,16-dien e (17) via th e 17-
h ydrazon e 15 an d th e 17-iodo-2,16-dien e (16) as above. Catalytic osm yl-
1
ation of 17 gave th e tetrol 18. Th e H NMR spectrum con tain ed sign als at
δ 3.80 (doublet, J = 5 Hz), δ 4.01 (m ultiplet), δ 4.30 (quartet J = 3 Hz) an d
δ 4.66 (m ultiplet) wh ich were assign ed to H-17, H-2, H-3 an d H-16, respec-
tively. Irradiation of th e H-18 sign al at δ 0.67 gave an NOE en h an cem en ts
of 4.7% to th e sign al at δ 3.80 an d 3.4% to th e sign al at δ 4.66, wh ilst irra-
diation of th e H-19 sign al at δ 0.82 gave an NOE en h an cem en t of 2.6% to
O
O
14
12 R = H
13 R = Ts
RO
H
H
NH2NH2•H2O
95%
NNH2
I
I2/NEt3
80%
16
15
Na/EtOH
80%
OH
OH
OsO4
55%
HO
18
H
OH
17
SCHEME 2
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Preparation of Androstanes Related to Aphidicolin
1549
th e sign al at δ 4.01. Th is, togeth er with m ultiplicity of th e H-3 sign al,
sh owed th at th e tetrol was th e 5α-an drostan e-2α,3α,16α,17α-tetrol (18).
In
con clusion
th e syn th eses of 5α-an drostan e-3α,4α,17β-triol,
5α-androstane-3α,4α,16α,17α-tetrol, 5α-an drostan e-2α,3α,16α,17α-tetrol as
aph idicolin m odels were described. Th e stereoch em istry of osm ylation fol-
lowed by acetylation of 5α-an drost-3-en -17β-ol was con firm ed by an X-ray
crystallograph y.
EXPERIMENTAL
Meltin g poin ts were determ in ed usin g an Electroth erm al IA 9200 apparatus an d are un cor-
rected. 1H NMR spectra were recorded in deuterioch loroform an d pyridin e-d5 with tetra-
m eth ylsilan e as an in tern al stan dard referen ce at 300 an d 500 MHz on a Bruker DPX 300
an d Bruker AMX 500 spectrom eters. 13C NMR spectra were recorded in deuterioch loro-
form at 75 an d 100 MHz on a Bruker DPX 300 an d Bruker AMX 500 spectrom eters. Ch e-
m ical sh ifts are given in ppm (δ-scale), couplin g con stan ts (J) are given in Hz. IR spectra
(waven um bers in cm –1) were recorded usin g Nujol m ulls on a Perkin –Elm er 1710 Fourier
tran sform spectrom eter. High -resolution m ass spectra (HRMS) were determ in ed on a Bruker
Dalton ics Apex III m ass spectrom eter operatin g in th e electrospray m ode. Th e X-ray an alysis
data collection was perform ed usin g KappaCCD. Th e refin em en ts were perform ed usin g
SHELXL-97 an d th e figures were drawn usin g ORTEP-3 for Win dows. A stock solution of
osm ium tetraoxide (1 g, 4 m m ol) in redistilled tert-butan ol (80 m l) con tain in g tert-butyl
h ydroperoxide (2 m l) was prepared an d stored at 0 °C. Extracts were dried over an h ydrous
sodium sulfate. Ligh t petroleum refers to th e fraction of b.p. 60–80 °C. Silica gel for ch rom a-
tograph y was Merck 9385.
5α-An drost-3-en e-17-on e (7)
Th is com poun d was prepared accordin g to th e literature procedure8. Yield 82%, m .p.
120–122 °C (lit.8 gives m .p. 121–123 °C). IR: 1725 (C=O). 1H NMR (300 MHz, CDCl3): 0.80 s,
3 H (H-18); 0.88 s, 3 H (H-19); 5.26 dd, 1 H, J(4,5) = 2.0, J(4,3) = 9.7 (H-4); 5.52 dq, 1 H,
J(3,2) = 3.0, J(3,4) = 9.7 (H-3).
5α-An drost-3-en -17-on e Hydrazon e (8)
Keton e8 7 (300 m g, 1.1 m m ol) in dry tetrah ydrofuran (15 m l) was h eated un der reflux with
trieth ylam in e (0.58 m l, 4.2 m m ol) an d h ydrazin e h ydrate (2 m l, 99%) for 3 h . Th e solution
was poured in to cold water (20 m l) an d th e m ixture cooled in ice. Th e precipitate was col-
lected an d wash ed with water to give th e h ydrazon e 8 (290 m g, 92%) wh ich was crystallized
from eth yl acetate as plates, m .p. 160–163 °C. For C19H30N2 (286.4) calculated: 79.67% C,
10.56% H, 9.78% N; foun d: 79.59% C, 10.48% H, 9.67% N. IR: 3172 (N-H). 1H NMR (300 MHz,
CDCl3): 0.70 s, 3 H (H-18); 0.88 s, 3 H (H-19); 4.74 bs, 2 H (NH2); 5.26 dd, 1 H, J(4,5) = 2.0,
J(4,3) = 9.7 (H-4); 5.52 dq, 1 H, J(3,2) = 3.0, J(3,4) = 9.7 (H-3). 13C NMR (75 MHz, CDCl3):
166.4, 131.2, 125.3, 53.7, 53.6, 45.9, 44.2, 35.0, 34.9, 34.2, 34.0, 31.4, 27.2, 24.3, 23.4, 23,3,
20.7, 17.1, 11.8.
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1550
Uyanik, Yildirim, Malay, Hanson, Hitchcock:
5α-An drost-2-en -17-on e Hydrazon e (15)
Un der sim ilar con dition s 5α-an drost-2-en -17-on e11 (14; 300 m g, 1.1 m m ol) gave th e
h ydrazon e 15 (300 m g, 95%) as a wh ite solid, m .p. 158–160 °C. For C19H30N2 (286.4) calcu-
lated: 79.72% C, 10.69% H, 9.80% N; foun d: 79.70% C, 10.63% H, 9.28% N. IR: 3170 (N-H),
1630 (C=C). 1H NMR (300 MHz, CDCl3): 0.78 s, 3 H (H-18); 0.86 s, 3 H (H-19); 4.75 bs, 2 H
(NH2); 5.55 m , 2 H (H-2 an d H-3). 13C NMR (75 MHz, CDCl3): 166.4, 125.8 (2 × C); 54.3,
53.6, 43.9, 41.4, 39.67, 34.9, 34.7, 34.2, 31.2, 30.2, 28.5, 24.3, 23.3, 20.5, 16.9, 11.6.
17-Iodo-5α-an drosta-3,16-dien e (9)
Th e h ydrazon e 8 (300 m g,1.05 m m ol) an d trieth ylam in e (1.4 m l, 10 m m ol) in dry tetra-
h ydrofuran (15 m l) was treated with a solution of iodin e (400 m g, 1.6 m m ol) in tetrah ydro-
furan (5 m l) at room tem perature un der n itrogen . After th e evolution of n itrogen h ad
ceased, th e solven t was evaporated an d th e residue was taken up in eth yl acetate. Th e ex-
tract was wash ed with dilute h ydroch loric acid, water, aqueous sodium sulfite, aqueous so-
dium h ydrogen carbon ate an d brin e, an d dried. Th e solven t was evaporated an d th e residue
ch rom atograph ed on silica gel. Elution with ligh t petroleum gave th e dien e 9 (320 m g,
80.5%) as a gum . IR: 1659 (C=C). 1H NMR (300 MHz, CDCl3): 0.74 s, 3 H (H-18); 0.80 s, 3 H
(H-19); 5.26 dd, 1 H, J(4,5) = 2.0, J(4,3) = 9.7 (H-4); 5.52 dq, 1 H, J(3,2) = 3.0, J(3,4) = 9.7
(H-3); 6.12 d, 1 H, J = 1.2 (H-16). 13C NMR (75 MHz, CDCl3): 137.4, 131.0, 125.5, 113.0,
54.5, 53.6, 50.1, 45.9, 36.2, 35.0, 34.6, 33.8, 33.7, 31.5, 27.2, 23.4, 20.8, 15.3, 11.8. HRMS:
for C19H27I calculated: 382.1150; foun d: 382.1148.
17-Iodo-5α-an drosta-2,16-dien e (16)
Un der sim ilar con dition s th e h ydrazon e 15 (280 m g, 0.97 m m ol) gave th e dien e 16 (300 m g,
80%) as a gum . IR: 1659 (C=C). 1H NMR (300 MHz, CDCl3): 0.74 s, 3 H (H-18); 0.78 s, 3 H
(H-19); 5.56 m , 2 H (H-2- an d H-3); 6.12 d, 1 H, J = 1.2 (H-16). 13C NMR (75 MHz, CDCl3):
137.4, 125.8 (2 × C); 112.9, 54.7, 54.3, 49.9, 41.5, 39.5, 36.2, 34.8, 34.6, 33.6, 31.3, 30.2,
28.5, 21.6, 15.2, 11.6. HRMS: for C19H27I calculated: 382.1162; foun d: 382.1180.
5α-An drosta-3,16-dien e (10)
Th e above iodoalken e 9 (250 m g, 0.6 m m ol) in eth an ol (40 m l) was treated with sodium
(2 g, 87 m m ol) un der reflux for 20 m in . Th e solution was cooled an d treated with 50%
aqueous eth an ol (40 m l). Th e eth an ol was evaporated in vacuo an d th e residue extracted
with eth yl acetate. Th e extract was wash ed with dilute h ydroch loric acid, aqueous sodium
sulfite, water an d brin e, an d dried. Th e solven t was evaporated an d th e residue was
ch rom atograph ed on silica gel. Elution with ligh t petroleum gave th e dien e 10 (140 m g,
83.5%) as an oil. IR: 1650 (C=C). 1H NMR (300 MHz, CDCl3): 0.76 s, 3 H (H-18); 0.78 s, 3 H
(H-19); 5.26 dd, 1 H, J(4,5) = 2.0, J(4,3) = 9.7 (H-4); 5.52 dq, 1 H, J(3,2) = 3.0, J(3,4) = 9.7
(H-3); 5.69 bs, 1 H (H-17); 5.84 dd, 1 H, J(16,15) = 1.8, J(16,17) = 4.7 (H-16). 13C NMR (75
MHz, CDCl3): 143.9, 131.4, 129.5, 125.4, 56.2, 54.2, 46.1, 45.7, 35.9, 35.2, 34.2, 33.9, 32.1,
29.7, 27.4, 23.5, 21.0, 17.1, 11.9. HRMS: for C19H28 calculated: 256.2191; foun d: 256.2200.
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1545–1552

Preparation of Androstanes Related to Aphidicolin
1551
5α-An drosta-2,16-dien e (17)
Un der sim ilar con dition s th e iodoalken e 16 (250 m g, 0.6 m m ol) gave th e dien e 17 (135 m g,
80.5%) as an oil. IR: 1640 (C=C). 1H NMR (300 MHz, CDCl3): 0.78 s, 3 H (H-18); 0.80 s, 3 H
(H-19); 5.56 m , 2 H (H-2 an d H-3); 5.69 d, 1 H, J(17,16) = 4.7 (H-17); 5.84 dd, 1 H, J(16,15) =
1.8, J(16,17) = 4.7 (H-16). 13C NMR (75 MHz, CDCl3): 143.9, 129.2, 125.9 (2 × C); 56.1, 54.8,
45.5, 41.6, 39.6, 35.9, 34.9, 34.2, 31.9, 31.8, 30.3, 28.7, 20.8, 17.0, 11.6. HRMS: for C19H28
calculated: 256.2195; foun d: 256.2200.
5α-An drostan e-3α,4α,17β-triol (5)
5α-An drost-3-en -17β-ol8 (4; 140 m g, 0.5 m m ol) in tert-butan ol (15 m l) an d water (15 m l)
was treated with potassium h exacyan oferrate(III) (1.65 g, 5 m m ol), potassium carbon ate
(690 m g, 5 m m ol), 1,4-diazobicyclo[2,2,2]octan e (56 m g, 0.5 m m ol) an d th e stock solution
of osm ium tetraoxide (0.4 m l) at 40 °C for 24 h . Sodium sulfite (140 m g, 1.1 m m ol) was
added an d th e solution was th en left to stir overn igh t. Th e m ixture was filtered an d ex-
tracted with eth yl acetate. Th e extract was dried an d th e solven t was evaporated to give th e
triol 5 (104 m g, 71%) wh ich was crystallized from eth yl acetate as n eedles, m .p. 194–196 °C.
For C19H32O3 (308.5) calculated: 74.00% C, 10.52% H; foun d: 73.65% C, 10.37% H. IR: 3490
(O-H). 1H NMR (500 MHz, pyridin e-d5): 0. 87 s, 3 H (H-18); 0.96 s, 3 H (H-19); 3.69 dd, 1 H,
J = 3.0, 11.0 (H-4); 3.83 t, 1 H, J = 8.5 (H-17); 4.28 q, 1 H, J = 3.0 (H-3). 13C NMR (100 MHz,
pyridin e-d5): 80.6, 71.1, 69.4, 55.2, 50.7, 45.4, 42.7, 36.9, 36.8, 34.8, 31.6, 31.1, 29.9, 27.3,
23.0, 22.5, 20.2, 12.3, 11.3. Th e triacetate 6, prepared with acetic an h ydride in pyridin e, h ad
m .p. 184–186 °C. IR: 1745 (C=O, acetate), 1716 (C=O, acetate). 1H NMR (300 MHz, CDCl3):
0.75 s, 3 H (H-18); 0.85 s, 3 H (H-19); 1.96 s, 3 H (17β-OAc); 2.0 s, 3 H (4α-OAc); 2.06 s, 3 H
(3α-OAc); 4.5 t, 1 H, J = 8.5 (H-17); 4.7 dd, 1 H, J = 3.0, 11.0 (H-4); 5.22 q, 1 H, J = 3.0 (H-3).
13C NMR (75 MHz, CDCl3): 171.65, 171.17, 170.89, 83.15, 72.71, 69.67, 54.49, 51.11, 44.22,
42.89, 37.89, 37.21, 35.17, 32.34, 31.13, 27.89, 25.61, 23.81, 22.65, 21.65, 21.57, 21.34,
20.71, 13.09, 12.50. HRMS: for C25H38O6 + Na calculated: 457.2560; foun d: 457.2562.
5α-An drostan e-3α,4α,16α,17α-tetrol (11)
Un der sim ilar con dition s th e dien e 10 (130 m g, 0.5 m m ol) gave th e tetrol 11 (100 m g, 61%)
as a wh ite powder, m .p. 234–236 °C. For C19H32O4·0.5H2O (333.5) calculated 68.41% C,
10.00% H; foun d: 68.37% C, 9.95% H. IR: 3470 broad (O-H). 1H NMR (500 MHz,
pyridin e-d5): 0. 70 s, 3 H (H-18); 0.85 s, 3 H (H-19); 3.67 dd, 1 H, J = 3.0, 11.0 (H-4); 3.82 d,
1 H, J = 5.3 (H-17); 4.28 q, 1 H, J = 3.0 (H-3); 4.67 q, 1 H, J = 5.3 (H-16). 13C NMR (100 MHz,
pyridin e-d5): 78.9, 71.6, 71.3, 69.7, 54.6, 47.6, 46.2, 45.2, 37.5, 36.1, 35.5, 32.6, 32.3, 32.1,
28.1, 23.4, 20.3, 17.5, 12.9.
5α-An drostan e-2α,3α,16α,17α-tetrol (18)
Un der sim ilar con dition s th e dien e 17 (130 m g, 0.5 m m ol) gave th e tetrol 18 (90 m g, 55%)
as a wh ite powder, m .p. 220–223 °C. IR: 3450 broad (O-H). 1H NMR (500 MHz, pyridin e-d5):
0.67 s, 3 H (H-18); 0.82 s, 3 H (H-19); 3.82 d, 1 H, J(16,17) = 5.0 (H-17); 4.01 m , 1 H (H-2);
4.30 q, 1 H, J = 3.0 (H-3); 4.67 m , 1 H (H-16). 13C NMR (100 MHz, pyridin e-d5): 78.9, 71.6,
71.2, 69.8, 54.7, 47.6, 45.6, 41.0, 39.8, 36.3, 36.1, 35.7, 32.6, 32.3, 30.8, 28.2, 20.3, 18.1,
12.9. HRMS: for C19H32O4 calculated: 324.2301; foun d: 324.2298.
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 11, pp. 1545–1552

1552
Uyanik, Yildirim, Malay, Hanson, Hitchcock:
X-ray Crystallograph ic Data an d Structure Determ in ation of
5α-An drostan e-3α,4α,17β-triyl Triacetate (6)
C25H38O6, Mr 434.55, orth orh om bic, space group P212121 (No. 19), a = 7.4107(2) Å, b =
10.4524(4) Å, c = 30.6454(13) Å, α = β = γ = 90°, V = 2373.78(15) Å3, Z = 4, Dcal = 1.22 g cm –3
,
µ = 0.09 m m –1, F(000) = 944. Data were collected on a crystal of size 0.10 × 0.02 × 0.02 m m 3
on a KappaCCD diffractom eter operatin g for 3.83 ≤ θ ≤ 25.1°. Reflection s of 9275 were col-
lected for –7 ≤ h ≤ 8, –12 ≤ k ≤ 11, –36 ≤ l ≤ 29. Th ere were 4057 in depen den t reflection s
with 2971 possessin g I > 2σ(I). Th e structure was solved by direct m eth ods an d refin ed usin g
SHELXL97. Th e fin al R in dices were [I > 2σ(I)] R1 = 0.057, wR2 = 0.115 an d (all data) R1
0.093 an d wR2 = 0.133. Th e largest differen ce peak an d h ole were 0.18 an d –0.19 e Å–3
=
.
CCDC 249909 con tain s th e supplem en tary crystallograph ic data for th is paper. Th ese
data can be obtain ed free of ch arge via www.ccdc.cam .ac.uk/con ts/retrievin g.h tm l (or from
th e Cam bridge Crystallograph ic Data Cen tre, 12, Un ion Road, Cam bridge, CB2 1EZ, UK;
fax: +44 1223 336033; or deposit@ccdc.cam .ac.uk).
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