The synthesis of functionalized 13,14-seco-steroids via Grob fragmentation

Article abstract of DOI:10.1016/j.steroids.2004.04.009

A synthetic methodology for the synthesis of 13,14-seco-steroids with substituents at C-14 and C-17 is described. The approach involves Grob fragmentation of 14β-hydroxy-17β-tosylates, hydroboration-oxidation of the intermediate Δ¹³⁽¹⁷⁾-olefin, and hydride reduction of the 14-ketone. An unambiguous structural assignment of (13R,14S,17S)-14,17- diacetoxy-3-methoxy-7α-methyl-13,14-secoestra-1,3,5(10)-triene was determined by X-ray analysis.

Full text of DOI:10.1016/j.steroids.2004.04.009

Steroids 69 (2004) 495–499
The synthesis of functionalized 13,14-seco-steroids
via Grob fragmentation
Vladimir A. Khripacha,∗, Vladimir N. Zhabinskiia, Galina P. Fandoa,
Alla I. Kuchtoa, Alexander S. Lyakhova, Alla A. Govorovaa,
Marinus B. Groenb, Jaap van der Louwb, Aede de Grootc
a
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Kuprevich str., 5/2, 220141 Minsk, Belarus
b
Department of Medicinal Chemistry, N.V. Organon, P.O. Box 20, 5340 BH Oss, The Netherlands
c
Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands
Received 9 December 2003; received in revised form 20 April 2004; accepted 27 April 2004
Abstract
A synthetic methodology for the synthesis of 13,14-seco-steroids with substituents at C-14 and C-17 is described. The approach involves
Grob fragmentation of 14␤-hydroxy-17␤-tosylates, hydroboration–oxidation of the intermediate ꢀ13(17)-olefin, and hydride reduction of
the14-ketone. Anunambiguousstructuralassignmentof(13R,14S,17S)-14,17-diacetoxy-3-methoxy-7␣-methyl-13,14-secoestra-1,3,5(10)-
triene was determined by X-ray analysis.
© 2004 Elsevier B.V. All rights reserved.
Keywords: Grob fragmentation; X-ray analysis; Secosteroids; Nine membered ring
1. Introduction
creation of steroidal hormone functionality in the resulting
nine membered ring or to the stereochemistry at C-13 after
cleavage of the C-13–C-14 bond.
The present paper describes a 13,14-seco-steroid synthesis
by Grob fragmentation of 14␤-hydroxy-17␤-tosylates and
further transformations, which lead to functionalized 13,14
seco-steroids. An X-ray analysis was performed to confirm
the structure of the final compound.
Our recent studies focused on the synthesis of 13,14-seco-
steroids [1–3] as new analogues of human steroids, which
posses a more flexible CD-ring in comparison with normal
tetracyclic steroid skeletons.
A small number of C-13–C-14-seco-steroids have
been isolated from natural sources [4–7], but the con-
figuration at C-13 has not been well established. Syn-
thetically useful routes to such compounds have been
hardly investigated. There are only a few examples of
13,14-seco-steroid syntheses, which date back to the be-
ginning of the 1960s. One of the described approaches
deals with the radical oxidation of 14␣-hydroxy steroids
[8,9]; the other one describes the Grob fragmentation of
14␤-hydroxy-17␣-tosylates [10–12]. It was shown that
Grob fragmentation of 14␤-hydroxy-17␣-tosylates gave
the expected ꢀ13(17)-14-ketones [11,12]. In the case of
14␣-hydroxy-17␤-tosylates a similar reaction proceeded
with the formation of 14␣,17␣-epoxide [10]. The reac-
tion pattern of 14␤-hydroxy-17␤-tosylates has never been
investigated, and also, no attention has been paid to the
2. Experimental
The detailed description of experimental details is given
in our previous article [2]. Crystal data and numerical details
of the structure determination are given in Table 1. 17,17-
(Ethylenedioxy)-3-methoxy-7␣ - methylestra - 1,3,5(10),15-
tetraene was supplied by Organon.
2.1. 3-Methoxy-7α-methylestra-1,3,5(10),15-tetraen-17-one
(2)
Compound 2 was prepared from 1 according to the pro-
cedure of Segaloff and Gabbard [13] in 92% yield. mp
1
193–195 ◦C (EtOAc) (Lit. [13] 191–194 ◦C). H NMR δ:
∗
Corresponding author. Tel./fax: +375 2 648 647.
E-mail address: khripach@iboch.bas-net.by (V.A. Khripach).
0.96 (d, J = 7 Hz, 3H, 7-Me), 1.11 (s, 3H, 18-H), 3.78 (s,
0039-128X/$ – see front matter © 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.steroids.2004.04.009

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V.A. Khripach et al. / Steroids 69 (2004) 495–499
Table 1
Crystal data and structure refinement for (13R,14S,17S)-14,17-diacetoxy-3-methoxy-7␣-methyl-13,14-secoestra-1,3,5(10)-triene (12)
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
C24H34O5
402.51
293(2)
0.71069
Orthorhombic
Space group
Unit cell dimensions
P212121
a = 9.498(3) Å, α = 90◦
b =11.530(3) Å, β = 90◦
c = 21.025(5) Å, γ = 90◦
Volume (Å3)
2302.3(10)
Z
4
Density (calculated) (mg/m3)
Absorption coefficient (mm−1
F (0 0 0)
1.161
0.080
872
1.94–27.56
)
Theta range for data collection (◦)
Index ranges
Reflections collected
0 ≤ h ≤ 12, 0 ≤ k ≤ 15, −1 ≤ l ≤ 27
3265
Independent reflections
Completeness to theta = 27.56◦
Absorption correction
3142 [R(int) = 0.0113]
100.0%
None
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Full-matrix least-squares on F
3142/0/267
1.024
Final R indices [I > 2σ(I)]
R indices (all data)
Absolute structure parameter
Largest difference (peak and hole) (eÅ−3
R1 = 0.0409, wR2 = 0.1051
R1 = 0.0595, wR2 = 0.1252
2.0(16)
0.134 and −0.147
)
3H, OMe), 6.10 (m, C16-H), 6.64 (d, J = 2.4 Hz, 1H, 4-H),
6.74 (dd, 1H, J = 8.5, 2.7 Hz, 2-H), 7.23 (d, 1H, J = 8.5 Hz,
1-H), 7.60 (d, 1H, J = 6 Hz, 15-H). 13C NMR δ: 12.9, 21.1,
25.9, 27.2, 29.5, 37.8, 38.0, 51.7, 53.0, 55.1, 111.8, 114.6,
126.5, 130.8, 132.2, 136.2, 157.8, 212.9.
water (0.6 ml) was added, followed by a 15%-solution of
NaOH (0.6 ml) and again water (1.8 ml). The residue was
filtered, the solvent was evaporated, and the residue was
chromatographed on silica gel (hexane–EtOAc = 5:1) to
give the alcohol 4 (2.11 g, 85%). mp 163–165 ◦C (EtOH)
(Lit. [14] 162–165 ◦C). IR (cm−1): 1630, 1520, 1465, 1325,
1
1265, 1250, 1045, 820. H NMR δ: 0.90 (d, J = 7 Hz, 3H,
2.2. 3-Methoxy-7α-methylestra-1,3,5(10),14-tetraen-
17-one (3)
7-Me), 0.99 (s, 3H, 18-H), 3.10 (dd, J = 17, 6 Hz, 1H, 6-H),
3.78 (s, 3H, OMe), 4.06 (dd, 1H, J = 9, 8 Hz, 17-H), 5.16
(m, 1H, 15-H), 6.62 (d, J = 2.4 Hz, 1H, 4-H), 6.74 (dd,
1H, J = 8.5, 2.7 Hz, 2-H), 7.22 (d, 1H, J = 8.5 Hz, 1-H).
13C NMR δ: 13.2, 16.0, 26.9, 27.8, 37.0, 38.1, 38.4, 39.0,
42.5, 47.1, 55.1, 83.5, 111.7, 114.6, 115.4, 127.2, 131.3,
136.6, 149.7, 157.6. HRMS Calc. for C20H27O2 (M + H)
299.2005; Found 299.2012.
Et3N (58.3 ml) and SiO2 (235 g, dried at 120 ◦C for 20 h)
were added to a solution of enone 2 (3.6 g, 12.2 mmol) in
EtOAc (725 ml). The reaction mixture was kept at 75 ◦C for
20 h. The silica gel was filtered, washed with EtOAc, and the
solvent was evaporated. The residue was chromatographed
on silica gel (hexane–EtOAc = 10:1) to give the deconju-
gated enone 3 (2.50 g, 69%). mp 138–140 ◦C (EtOAc) (Lit.
[14] 142–144 ◦C). IR (cm−1): 1770, 1630, 1520, 1290, 1280,
2.4. 17β-Hydroxy-3-methoxy-14β,15β-epoxy-7α-
methylestra-1,3,5(10)-triene (5)
1
1260, 1060. H NMR δ: 0.98 (d, J = 7 Hz, 3H, C7-Me),
1.15 (s, 3H, 18-H), 3.78 (s, 3H, OMe), 5.62 (br.s, 1H, 15-H),
6.64 (d, J = 2.4 Hz, 1H, 4-H), 6.74 (dd, 1H, J = 8.5, 2.7 Hz,
2-H), 7.24 (d, 1H, J = 8.8 Hz, 1-H). 13C NMR δ: 13.3, 20.9,
26.8, 26.9, 32.2, 37.4, 38.7, 41.4, 42.3, 50.9, 55.1, 111.8,
114.1, 114.8, 127.0, 130.9, 136.4, 150.1, 157.7, 221.7.
A solution of homoallylic alcohol 4 (2.60 g, 8.72 mmol)
and 70% MCPBA (4.29 g, 17.4 mmol) in CHCl3 (50 ml) was
kept at room temperature for 40 min. The reaction mixture
was washed with 10% NH4OH, then with water, and the
organic layer was dried (Na2SO4). The solvent was evap-
orated, and the residue was chromatographed on silica gel
(hexane–EtOAc = 4:1) to give the epoxide 5 (1.59 g, 58%).
mp 179–180 ◦C (EtOH). IR (cm−1): 1615, 1510, 1475, 1240,
1170, 1100, 1030. 1H NMR δ: 0.82 (d, J = 6.7 Hz, 3H,
7-Me), 1.14 (s, 3H, 18-H), 3.05 (dd, J = 16, 5 Hz, 1H, 6-H),
2.3. 17β-Hydroxy-3-methoxy-7α-methylestra-1,3,5(10)14-
tetraene (4)
LiAlH4 (0.64 g, 17 mmol) was added to a solution of ke-
tone 3 (2.50 g, 8.44 mmol) in THF (50 ml). After 15 min

V.A. Khripach et al. / Steroids 69 (2004) 495–499
497
3.78 (s, 3H, OMe), 3.83 (s, 1H, 17-H), 6.62 (d, J = 2.7 Hz,
1H, 4-H), 6.74 (dd, 1H, J = 8.5, 2.7 Hz, 2-H), 7.20 (d,
1H, J = 8.9 Hz, 1-H). 13C NMR δ: 13.6, 14.3, 24.0, 27.5,
34.5, 36.1, 37.2, 39.6, 39.9, 46.5, 55.1, 61.8, 74.0, 77.0,
112.0, 114.7, 127.1, 131.0, 136.5, 157.8. HRMS Calc. for
C20H27O3 (M + H) 315.1954; Found 315.1936.
52%). mp 103–105 ◦C (EtOH). IR (cm−1): 1710, 1620,
1510, 1465, 1325, 1245. 1H NMR δ: 0.95 (d, 3H, J = 7 Hz,
7-Me), 1.87 (s, 3H, 18-H), 3.78 (s, 3H, OMe), 5.44 (m, 1H,
17-H), 6.50–7.30 (m, 3H, arom. H). 13C NMR δ: 16.8, 18.6,
21.6, 29.1, 34.6, 38.4, 39.6, 40.6, 41.8, 55.0, 59.8, 112.4,
112.9, 122.6, 129.4, 131.5, 137.8, 138.1, 156.9, 217.7.
HRMS Calc. for C20H27O2 (M + H) 299.2005; Found:
299.2010.
2.5. 14β,17β-Dihydroxy-3-methoxy-7α-methylestra-1,3,5
(10)-triene (6)
2.8. (14S)-14-Hydroxy-3-methoxy-7α-methyl-13,14-
secoestra-1,3,5(10),13(17)(E)-tetraene (9)
A mixture of epoxide 5 (700 mg, 2.23 mmol) and LiAlH4
(510 mg, 13.4 mmol) in ether (60 ml) was refluxed for 8 h.
Then, water (0.5 ml), 15% NaOH (0.5 ml) and again water
(1.5 ml) were added. The precipitate was filtered off, and the
filtrate was evaporated. The residue was chromatographed
on SiO2 (petroleum ether–EtOAc = 2:1) to give the diol 6
(644 mg, 92%). mp 200–204 ◦C (EtOH). IR (cm−1): 1630,
LiAlH4 (51.7 mg, 1.36 mmol) was added to a solution
of ketone 8 (50 mg, 0.17 mmol) in Et2O (2 ml). The re-
action mixture was stirred for 20 min at RT, and then,
water (0.05 ml), NaOH solution (15%, 0.05 ml) and again
water (0.15 ml) were added. The precipitate was filtered
off, and the filtrate was evaporated. The residue was chro-
matographed on SiO2 (hexane–EtOAc = 8:1) to give al-
cohol 9 (44 mg, 87%) as an oil. IR (cm−1): 1620, 1510,
1450, 1270, 1255, 1045. 1H NMR δ: 1.10 (d, J = 7 Hz, 3H,
7-Me), 1.62 (s, 3H, 18-H), 3.74 (s, 3H, OMe), 4.04 (m, 1H,
14-H), 5.40 (m, 1H, 17-H), 6.54 (d, 1H, J = 2 Hz, 1-H),
6.70 (dd, 1H, J = 8, 2 Hz, 2-H), 7.02 (d, 1H, J = 8 Hz,
4-H). 13C NMR δ: 17.5, 19.5, 24.3, 27.5, 35.2, 36.0, 36.4,
37.2, 40.6, 44.5, 55.2, 70.9, 112.4, 112.9, 127.9, 130.5,
133.2, 133.7, 138.8, 157.0. HRMS Calc. for C20H29O2 (M
+ H) 301.2162; Found: 301.2158.
1
1515, 1465, 1445, 1250, 1090. H NMR δ: 0.92 (d, 3H, J
= 7 Hz, 7-Me), 1.10 (s, 3H, 18-H), 3.64–3.86 (m, 1H, 17-H),
3.78 (s, 3H, OMe), 6.56–7.26 (m, 3H, arom. H). 13C NMR
δ: 13.4, 14.5, 24.7, 27.8, 31.2, 33.0, 33.6, 34.0, 40.6, 46.7,
50.2, 55.1, 81.8, 85.1, 111.9, 114.3, 127.4, 131.2, 136.5,
157.4.
2.6. 14β-Hydroxy-17β-toluenesulfonyloxy-3-methoxy-7α
-methylestra-1,3,5(10),14-triene (7)
A mixture of diol 6 (400 mg, 1.27 mmol), TsCl (400 mg,
2.10 mmol), and pyridine (3 ml) was kept at 30 ◦C for 5 h.
Then, it was diluted with water and extracted with EtOAc
and CHCl3. The combined extracts were dried (Na2SO4)
and evaporated. The residue was chromatographed on SiO2
(toluene–EtOAc = 10:l) to give the tosylate 7 (429 mg,
72%). mp 137–140 ◦C (hexane). IR (cm−1): 1615, 1510,
2.9. (13R,14S,17S)-14,17-Dihydroxy-3-methoxy-7α-
methyl-13,14-secoestra-1,3,5(10)-triene (10)
A mixture of 9 (330 mg, 1.1 mmol) and BH3·THF (1 M,
15 ml) was stirred for 1.5 h at ambient temperature. Then, it
was cooled to 0 ◦C, and H2O (1 ml), NaOH (2 M, 0.5 ml),
and H2O2 (30%, 0.5 ml) were added consecutively. The re-
action mixture was stirred for 30 min, diluted with water,
and extracted with CHCl3 and EtOAc. The extracts were
dried (Na2SO4), and evaporated, and the residue was chro-
matographed on SiO2 (hexane–EtOAc = 1:1) to give diol
10 (200 mg, 57%). mp 103–107 ◦C (EtOH). IR (cm−1):
1
1480, 1370, 1240, 1180, 900. H NMR δ: 0.87 (d, 3H, J
= 1 Hz, 7-Me), 0.95 (s, 3H, 18-H), 2.45 (s, 3H, OTs), 3.76
(s, 3H, OMe), 4.52 (d, 1H, J = 6.5 Hz, 17-H), 6.60 (d, 1H,
J = 2.7 Hz, 4-H), 6.70 (dd, 1H, J = 8.5, 2.7 Hz, 2-H), 7.16
(d, 1H, J = 8.5 Hz, OTs), 7.34 (m, 2H, OTs and arom. H),
7.80 (d, 1H, J = 8.2 Hz, OTs). 13C NMR δ: 13.7, 14.5,
21.7, 24.7, 27.7, 29.3, 33.0, 33.9, 34.2, 40.7, 46.7, 50.8,
55.1, 83.8, 91.6, 112.0, 114.4, 127.4, 127.8, 129.8, 130.9,
134.2, 136.7, 144.7, 157.6.
1
1620, 1510, 1470, 1275, 1050, 800. H NMR and 13C (see
Fig. 1). HRMS Calc. for C20H31O3 (M + H) 319.2267;
Found 319.2274.
2.7. Grob fragmentation of (7)
2.10. Acetylation of the diol (10)
A mixture of DMSO (5 ml) and NaH (80%, 288 mg,
9.6 mmol) was stirred under argon at 40 ◦C for 1 h [15].
Then a solution of tosylate 7 (290 mg, 0.64 mmol) in DMSO
(3 ml) was added, and the mixture was kept at 40 ◦C for 1 h.
It was subsequently diluted with brine and extracted with
EtOAc. The extract was dried (Na2SO4) and evaporated,
and the residue was chromatographed on SiO2 (petroleum
ether–EtOAc = 10:1) to give 3-methoxy-7␣-methyl-13,14-
secoestra-1,3,5(10),13(17)E-tetraen-14-one (8) (100 mg,
Ac2O (0.1 ml) was added to a solution of diol 10 (47 mg,
0.147 mmol) in pyridine (0.2 ml). The reaction mixture
was stirred at RT for 4 h and diluted with water. This
mixture was extracted with CHCl3 and EtOAc, and the
extracts were dried (Na2SO4). The solvents were evap-
orated, and the residue was chromatographed on SiO2
(hexane–EtOAc = 7:1) to give: (a) (13R,14S,17S)-14,17-
diacetoxy-3-methoxy-7␣-methyl-13,14-secoestra-1,3,5(10)-

498
V.A. Khripach et al. / Steroids 69 (2004) 495–499
Scheme 1.
Fig. 1. 1H and 13C assignment for compound 10.
with LiAlH4 did not affect the ꢀ14-double bond and led
smoothly to the homoallylic alcohol 4 [14]. Its epoxidation
proceeded with formation of the 14␤,15␤-epoxide 5 as the
main product. The hydride reduction of 5 afforded diol 6,
which was transformed into tosylate 7. Finally, the Grob
fragmentation [17,18] of 7 gave the desired seco-steroid 8
in a reasonable 52% yield. It can thus be concluded that the
14␤-hydroxy-17␤-tosylate also undergoes a Grob fragmen-
tation reaction, although its conformation is not optimal for
such a fragmentation.
triene (12) (17 mg, 28%). mp 120–124 ◦C (EtOH). IR
(cm−1): 1745, 1620, 1510, 1470, 1380, 1250, 1025. 1H
NMR δ: 0.98 (d, J = 7 Hz, 18-H or 7-Me), 1.02 (d, J
= 7 Hz, 18-H or 7-Me), 1.65 (s, 3H, OAc), 2.05 (s, 3H,
OAc), 3.71 (s, 3H, OMe), 4.85 (m, 1H, 14- or 17-H), 5.30
(m, 1H, 17- or 14-H), 6.50 (d, 1H, J = 2 Hz, 4-H), 6.70
(dd, 1H, J = 8, 2 Hz, 2-H), 7.10 (d, 1H, J = 8 Hz, 1-H).
13C NMR δ: 18.8, 20.2, 21.0, 21.7, 24.4, 24.8, 26.3, 28.0,
29.2, 32.1, 35.1, 35.3, 35.7, 55.1, 72.7, 77.4, 112.0, 112.3,
129.4, 132.3, 138.2, 156.9, 170.5, 170.7; (b) (13R,14S
17S)-14-hydroxy-17-acetoxy-3-methoxy-7␣-methyl-13,14-
secoestra-1,3,5(10)-triene (11) (16.8 mg, 32%). mp 110–
114 ◦C (EtOH). IR (cm−1): 1740, 1620, 1510, 1470, 1380,
According to the NMR data, the obtained sample seemed
to contain about 15% of another steroid, which at first
was presumed to be the (Z)-isomer of the olefin 8. How-
ever, careful study of the NMR spectra led us to the con-
clusion that this compound could be an (E)-cyclononene
derivative as well. From the (E)-cyclononene compound
␤-caryophyllene, it is known that four conformations are
possible [19]. It is likely that another conformer of com-
pound 8 was seen as a distinct species at normal temperature
1
1255, 1050, 750. H NMR δ: 1.05 (d, J = 7 Hz, 18-H or
7-Me), 1.75 (d, J = 7 Hz, 18-H or 7-Me), 2.05 (s, 3H,
OAc), 3.76 (s, 3H, OMe), 4.10 (m, 1H, 14-H), 4.40 (m, 1H,
17-H), 6.51 (d, 1H, J = 2 Hz, 4-H), 6.70 (dd, 1H, J = 8,
2 Hz, 2-H), 7.12 (d, 1H, J = 8 Hz, 1-H). 13C NMR δ: 19.0,
20.3, 21.1, 25.1, 26.2, 28.2, 28.7, 29.5, 29.7, 30.9, 35.2,
35.9, 36.5, 55.1, 70.8, 77.7, 112.4, 112.9, 129.5, 132.2,
139.0, 157.0, 170.9.
1
in the H and 13C NMR spectra.
The hydride reduction of
8 proceeded smoothly
with formation of only one isomer 9 using NaBH4,
Ca(BH4)2, or LiAlH4 (Scheme 2). To our surprise, the
hydroboration–oxidation [20] of 9 also led to only one
product 10. Molecular models showed that indeed the dou-
ble bond in 9 was oriented in such a way that borane attack
from the inner side of the nine-membered ring was not pos-
sible. The preparation of compounds without a substituent
at C-14 can be performed using the approaches described
by us earlier [3].
3. Results and discussion
Enone 2 proved to be a good starting material for the
preparation of the desired hydroxy tosylate which could then
be subjected to Grob fragmentation. The ␣,␤-unsaturated
ketone 2 [13] was obtained by removal of the ketal pro-
tecting group (Scheme 1), and deconjugation of the enone
system in 2 was achieved by treatment with Et3N and
SiO2 [16]. Reduction of the ␤,␥-unsaturated ketone 3 [14]
The NMR spectra of 10 (Fig. 1) were markedly different
from the normal 7␣-methyl steroids [21]. Due to a flip of ring

V.A. Khripach et al. / Steroids 69 (2004) 495–499
499
pach and E.V. Skorodumov for recording the NMR spectra
and Dr. E. van Bulen and Ms. J. Verhoosel for exact mass
measurements.
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Fig. 2. ORTEP view of (13R,14S,17S)-14,17-diacetoxy-3-methoxy-7␣-
methyl-13,14-secoestra-1,3,5(10)-triene (12).
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density functional evaluations of the molecular conformations
B, the 7␣-methyl group and the C-8 and C-9 protons were
more or less equatorial, which resulted in a J ∼ 0 Hz between
the two protons, although they were trans. The C-9–C-11
bond and the C-8–C-14 bond were axial, sticking up and
down, respectively, and the angle between H-8 and H-14 is
approximately 90◦ (J ∼ 0 Hz). This minimized the steric in-
teraction between the 7-methyl group and C-14/C-15. The
protons at C-9, C-13, and C-16 were on the inside of the
9-membered ring (NOE contacts). An unambiguous assign-
ment of the configuration at C-13, C-14, and C-17 for com-
pounds 16–19 could not be done based on NMR data only.
This problem was solved with the synthesis of diacetate 19,
which produced a crystal suitable for X-ray analysis (Fig. 2
and Table 1).
In conclusion, the synthesis of compounds possess-
ing a substituted C-13–C-14 seco-steroidal skeleton was
accomplished using a Grob fragmentation reaction of a
14␤-hydroxy-17␤-tosylated steroid.
of ␣-caryophyllene and 6-hydroxycaryophyllene.
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26.
Acknowledgements
The authors are indebted to Organon International for fi-
nancial support of this research. We thank Dr. N.B. Khri-