P -TsOH-Catalyzed one-pot transformation of di- and trihydroxy steroids towards diverse A/B-ring oxo-functionalization

Article abstract of DOI:10.1039/c7nj01878a

A solid support-mediated p-TsOH-catalyzed milder transformative protocol was developed to furnish diverse ring-A and/or ring-B oxo-functionalized steroids. To furnish interesting isomers involving the A/B-ring of biomolecules in a one-pot approach, only solid supports (and not solution!) were found to be effective. p-TsOH/SiO₂-oxidation of 4β-hydroxycholesterol, the major oxysterol in human circulation, into a mixture of cholest-4-en-3-one, cholest-4-ene-3,6-dione, and 5α-cholestane-3,6-dione was the starting point for the investigations herein. The reaction protocol was optimized in detail, and efforts were carried out toward gaining an understanding of the mechanistic aspects favoring the solid support, and a possible synergetic catalytic system involving p-TsOH and SiO₂ was expected to be a key part. Application of the novel methodology to 4β,7α-dihydroxy steroids resulted in the desired diverse ketosteroids through oxidation/oxidative dehydration, which generalized the process as a facile multi-oxo-functionalization steroidal transformation.

Full text of DOI:10.1039/c7nj01878a

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Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
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DOI: 10.1039/C7NJ01878A
p-TsOH-Catalyzed one-pot transformation of di- and trihydroxy
steroids towards diverse A/B-ring oxo-functionalization†
Antara Sarkar,a Jayanta Dasa and Pranab Ghosh*
Natural Products and Polymer Chemistry Laboratory, Department of Chemistry, North Bengal
University, Darjeelingꢀ734013, India
†Electronic Supplementary Information (ESI) available: Natural sources of various ketosteroids;
schematic presentations for the earlier laboratory syntheses of various ketosteroids related to this
paper; schematic presentations for the bioconversion routes to some ketosteroids; biological
reports of some ketosteroids and copies of 1H and 13C NMR spectra of the isolated products. See
DOI: 10.1039/x0xx00000x
aThese authors contributed equally to this paper.
*Corresponding author. Fax: +91 353 2699 001; Tel: +91 353 2776 381; email: pizy12@yahoo.com
Abstract
A solid supportꢀmediated pꢀTsOHꢀcatalyzed milder transformative protocol is developed to
furnish diverse ringꢀA and/or ringꢀB oxoꢀfunctionalized steroids. To flourish interesting isomers
involving A/Bꢀring of the biomolecules in oneꢀpot, only solidꢀsupports (and not solution!) were
effective. pꢀTsOH/SiO2ꢀOxidation of 4β−hydroxycholesterol, the major oxysterol in human
circulation, into a mixture of cholestꢀ4ꢀenꢀ3ꢀone, cholestꢀ4ꢀeneꢀ3,6ꢀdione and 5αꢀcholestaneꢀ3,6ꢀ
dione was the starting endeavor to further the present scope. The reaction protocol was optimized
in detail, and efforts toward the mechanistic understanding favoring the solid support were also
evaluated, and a possible synergetic catalytic system involving pꢀTsOH and SiO2 is expected.
Application of the novel methodology to 4β,7αꢀdihydroxy steroids results the desired diverse

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ketosteroids through oxidation/oxidative dehydration which generalizes the process as a facile
multiꢀoxoꢀfunctionalization steroidal transformation.
1. Introduction
Oxysteroids, the steroids having oxygen bearing functionalities, are the major steroid derivatives
which owe prime attention both from chemical as well as biological perspective.1 And among the
oxysteroids, different ketosteroids where one or more carbonyl (>C=O) functionality is/are
distributed in different steroidal skeletal position, reveal the wide scope of having a variety of
biological activities depending on the various isomeric options available. On the other hand,
these particular oxysteroids are distributed in nature widely having the basic skeleton of
cholesterol or βꢀsitosterol, for the former is the major zoosteroid whereas the latter is the most
abundant phytosteroid.
Nature remains the major source of ketosteroids from the very early stages, and
especially marine plants and animals are the richest source of them. The major natural
ketosteroids of cholesterol and βꢀsitosterol skeleton2 areꢀ cholestenone (1),3 stigmastenone (2),3b,
3e,4
cholestꢀ4ꢀeneꢀ3,6ꢀdione (3),3cꢀ3e stigmastꢀ4,6ꢀdione (4),3c,3d βꢀsitostꢀ4ꢀeneꢀ3,6ꢀdione (16),5,6
5αꢀcholestaneꢀ3,6ꢀdione (5),7 5αꢀbetasitostaneꢀ3,6ꢀdione (6),8ꢀ9 cholestaꢀ3,5ꢀdieneꢀ7ꢀone (9),3h,10
stigmastaꢀ3,5ꢀdieneꢀ7ꢀone (10)11 and cholestaꢀ4,6ꢀdieneꢀ3ꢀone (11)3h (Fig. 1). Besides, there are
a number of bioactive natural steroids having the similar ketoꢀfunctionality which do not have
the exact cholesterol or βꢀsitosterol skeleton, e.g., 5αꢀdiones 7 and 8,12 and enediones 12 and
1313 (Fig. 1).
R1
R
R2
H
H
H
H
R3
H
H
H
H
H
H
H
O
H
H
O
H
H
O
H
O
O
O
H
1; R= H
2; R= C2H5
O
4
3
5; R1= R2 = H, R3= CH3
6; R1= H, R2= C2H5, R3= CH3
7; R1= H, R2= -CH=C-CH3, R3= CH3
8; R1= OH, R2= R3= H
R
R
H
H
H
H
H
H
HO
H
H
O
H
H
EtO2C
O
O
O
9; R= H
10; R= C2H5
O
12a; R= H
12b; R= C2H5
11
O
13
Fig. 1 Natural ketosteroids.

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Besides different biological activities of various ketosteroids,14 some cholesterolꢀbased
derivatives are correlated with their profound and direct implications in human biology. For
example, cholestenone (1) was found in LDL and VLDL of normal human whereas cholestaꢀ3,5ꢀ
dienꢀ7ꢀone (9) was reported to be present in plasma of normal and diabetic human subjects,10d
and in normal human liver and alcoholic fatty liver.10f It was found also in human atherosclerotic
lesions and was found to be a decomposition product of 7ꢀketocholesterol.10g Human gallstones
and gallbladder bile also were found to contain cholestꢀ4ꢀenꢀ3ꢀone (1), cholestaꢀ4,6ꢀdieneꢀ3ꢀone
(11) and cholestaꢀ3,5ꢀdienꢀ7ꢀone (9).3h Many of the important steroidal hormones viz.,
progesterone, testosterone, aldosterone etc., are structurally ketoꢀsteroids and in addition, there
are a number of marketed drugs, based on various ketosteroid structures, available for various
therapeutic applications.15
A number of successful syntheses of different ketosteroids are reported earlier. People
have utilized different appropriate starting compounds for the syntheses depending upon the
scope of the respective transformative reactions. Schematic presentations for the earlier
laboratory syntheses of the various ketosteroids related to this paper are provided in section ES2
in the Electronic Supplementary Information (ESI). These include16 cholestenone (1);17; cholestꢀ
4ꢀeneꢀ3,6ꢀdione (3);10e,18 5αꢀcholetaneꢀ3,6ꢀdione (5);17b,18a,19 Cholestaꢀ3,5ꢀdienꢀ7ꢀone (9);10e,18a,20
Cholestaꢀ4,6ꢀdienꢀ3ꢀone (11)18b,19b,21 and 5αꢀCholestaneꢀ4,7ꢀdione (22).22 In addition, a number
of conjugated ketosteroids were also found to be the bioconversion products of suitable
substrates (please follow section ES3 in Electronic Supplementary Information, ESI for an
schematic presentation).10e,18rꢀ18t,23
In analogy to the fact that there are limited attempts of the transformative reactions of
natural products with green chemistry concern, none of the reported syntheses of these
ketosteroids include the consideration of the green chemistry principles. In this juncture, the
present work demonstrates a truly greenꢀsteered oneꢀpot transformation to the isomeric
ketosteroids, all starting from the highly useful and easily available24 biomoleculesꢀ the
dihydroxyꢀ and trihydroxy steroids.
Thus, in brief, considering the significant usefulness of the ketosteroids, on the
perspective of potential biological activities, and new synthetic approaches we envisioned to
design the present investigation utilizing some oxysteroid biomolecules as the starting materials
such as 4βꢀhydroxyꢀ and 4β,7αꢀdihydroxy derivatives of cholesterol and βꢀsitosterol. On the

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other hand, considering the present day requirement of green chemistry applications, we tried
attempting the transformations on solventꢀfree solid supports which, to our surprise, resulted to
achieve in a facile, singleꢀstep and greener approach, diverse oxoꢀfunctionalized steroids, many
of which were interestingly isomeric through the involvement of the ringꢀA and/ or ꢀB of the
steroid skeleton.
2. Results and discussion
In concise, the present work describes the solid support/ pꢀTsOHꢀcatalyzed transformations of
4βꢀhydroxyꢀ and 4β,7αꢀdihydroxy derivatives into various (but selective) corresponding ringꢀA
and/ or ringꢀB ketosteroids (Scheme 1 and Scheme 3). Whereas in solution, the reaction ended
up producing a single derivative (please follow captions for Schemes 1 and ꢀ3), on the solid
supports, 4βꢀhydroxy steroids yielded the corresponding 4ꢀeneꢀ3ꢀones, 4ꢀeneꢀ3,6ꢀdiones and 5αꢀ
3,6ꢀdiones; and 4β,7αꢀdihydroxy steroids produced the corresponding 5ꢀeneꢀ7ꢀones, ꢀ3,5ꢀdieneꢀ
7ꢀones, ꢀ4,6ꢀdieneꢀ3ꢀones and 5αꢀ4,7ꢀdiones (Schemes 1 and ꢀ3).
R
R
R
R
p-TsOH/ SiO2
+
+
120oC, 10 min.
HO
O
O
O
H
1; R= a
2; R= b
OH
O
14; R= a
15; R= b
O
3; R= a
16; R= b
5; R= a
6; R= b
R: a=
,
b=
Scheme 1. Solid supportꢀ driven steroidal oxoꢀfunctionalization: pꢀTsOH/SiO2 on 4βꢀhydroxy
steroids. In solution phase (in ethanol and dichloromethane) the diols 14 and 15 produce only 1 and 2
respectively. (1 and 2 were isolated respectively at 64% and 57% yield in DCM; 60% and 56% in
ethanol)
2.1 Preparation of the starting materials
The starting materials for the present work, as mentioned above, wereꢀ 4βꢀhydroxy (the diols, 14
and 15) and 4β,7αꢀdihydroxy (the triols, 17 and 18) derivatives of cholesterol and βꢀsitosterol.
These biomolecules were synthesized easily from the respective parent steroids by the oxidation

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with selenium dioxide. The triols were also prepared from the diols after the treatment with same
reagent. Detailed syntheses can be found elsewhere.24
2.2 Optimization of the reaction conditions
During the test reactions, when 4βꢀhydroxy cholesterol (14) was heated with pꢀTsOH on
activated silica, three products isolated were analyzed as cholestꢀ4ꢀenꢀ3ꢀone (1), cholestꢀ4ꢀeneꢀ
3,6ꢀdione (3) and 5αꢀcholestaneꢀ3,6ꢀdione (5) (Scheme 1). The reaction was attempted in
solution phase also using dichloromethane (DCM) and ethanol separately as solvents which
yielded, at room temperature (5ꢀ10 min.), cholestꢀ4ꢀenꢀ3ꢀone (1, 64% and 60% from DCM and
ethanol respectively) only and allowing the reaction for longer time (upto 45 min.) did not yield
eneꢀdione 3 and/ or dione 5 at all (by careful TLC experiments). Thus, it was concluded,
presumably, that solid silica directed, somehow, the formation of the products 3 and 5. Then for
the preliminary optimization of the reaction conditions we planned to perform the reaction (with
pꢀTsOH primarily at 120 mol%) at three different temperatures, viz., at 60oC, 120oC and 180oC
using silica gel 60ꢀ120 mesh as the reaction medium (Table 1; entries 1ꢀ3). The reactions at
120oC and 180oC resulted, in a very short time (5ꢀ10 minutes), comparable product distribution
(Table 1, entries 2, 3); whereas at 60oC the reaction took longer time (2 h) for its completion and
moreover, cholestꢀ4ꢀeneꢀ3,6ꢀdione (3) and 5αꢀcholestaneꢀ3,6ꢀdione (5) were produced at lower
yields (Table 1, entry 1). As our main focus, at this stage, was to emphasize the formation of
compounds 3 and 5, we found it suitable to carry out further optimization reactions at 120oC and
180oC. And considering the anticipated catalytic potentiality of pꢀTsOH,26 the reactions were
carried out taking different amount of the reagent, ranging from 30ꢀ240 mol% (Table 1, entries
4ꢀ9). Analyzing the isolated yields from all the reactions, 60 mol% reagent and 120oC was found
to be the optimum reaction condition (Table 1, entry 6). Though at 180oC and 60 mol% pꢀTsOH,
the yield of the compounds 3 and 5 was little bit higher, the overall conversion was not
satisfactory and hence was not chosen as the optimum reaction temperature (Table 1, entries 7ꢀ
8).

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Table 1. Optimization of the reaction conditions taking 4βꢀhydroxycholesterol (14) and pꢀ
toluenesulfonic acid on activated silica.a
Entry
pꢀTsOH (mol%)
Temperature (oC)
Time (min.)
Yieldb %
1
3
5
1
2
3
4
5
6
7
8
9
120
120
120
30
60
120
10
05
10
05
10
05
10
10
55
45
41
44
40
55
35
27
44
07
06
10
06
04
05
10
10
11
<1
120
180
120
180
120
180
180
120
08
08
06
08
10
12
13
05
30
60
60
60
240
aAll the reactions were performed on 100 mg (0.248 mmol) of substrate and on 4 g mmolꢀ1 of activated
b
silica (60ꢀ120 mesh). Isolated pure products by column chromatography.
At the optimized reaction condition, various potential and useful solid supports were then
employed as the reaction media (Table 2). However, the reaction was first tested without any
solid support which furnished only cholestenone 1 at 53% yield and no 3 and 5 at all (Table 2,
entry 1). Silica gel 60ꢀ120 mesh, usually used for the column chromatography produced better
result in comparison to silica gel Fꢀ254. Both neutral and acidic alumina gave lower yields of
compounds 3 and 5. Montmorillonite KSF, a well applicable clay in the solid phase organic
reactions, produced the expected compounds at lower yields in comparison to silica gel 60ꢀ120.
Eneꢀdione 3 and dione 5 were not produced at all from 4Å molecular sieves; only cholestenone 1
was isolated at trace amounts.

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Table 2. Optimization of solid supports taking 4βꢀhydroxycholesterol (14) and pꢀTsOH.a
Entry
Solid supportb
Yieldc %
1
53
55
58
40
46
36
3
5
1
2
3
4
5
6
7
Neat
Silica 60-120d
NF
10
05
03
02
07
NF
10
05
06
03
07
NF
Silica Fꢀ254
Alumina Neutral
Alumina acidic
Montmorillonite KSF
4Ǻ molecular sievese
Tracesf NF
aAll the reactions were performed on 100 mg (0.248 mmol) of substrate (4βꢀhydroxycholesterol) and
60 mol% of reagent (pꢀTsOH) and for 10 minutes at 120oC. bAll preactivated solid supports were used at
c
60 mol% amount.
Isolated pure compounds from column chromatography. dUnder dinitrogen
e
atmosphere the three products were isolated at 62, 5 and 8% of yield respectively. 65% of unreacted
f
substrate was recovered. No product was isolated through column chromatography though TLC pointed
its formation. NF = not found.
The variation of the amount of silica gel used in the reaction was then performed to observe
that whether it can alter the yield distribution. Detailed experiments showed (Table 3) that 3g
and above of silica gel per mmol of substrate produced comparable yields of the three products.
Table 3. Optimization of the amount of silica 60ꢀ120 mesh for the reaction of 4βꢀhydroxy
cholesterol (14) with pꢀTsOH.a
Entry
Silica (60ꢀ120) mesh
Yieldb %
1
3
5
1
2
3
4
5
6
100 mg (0.5 g mmolꢀ1)
250 mg (1 g mmolꢀ1)
500 mg (2 g mmolꢀ1)
750 mg (3 g mmolꢀ1)
1g (4 g mmol-1)
47
50
50
52
55
57
4
3
5
4
5
7
9
10
10
10
10
7
1.5g (6 g mmolꢀ1)

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7
2g (8 gmmolꢀ1)
58
7
9
aAll the reactions were performed on 100 mg (0.248 mmol) of substrate (4βꢀhydroxycholesterol) and 60
b
mol% of reagent (pꢀTsOH) and for 10 minutes in 120oC. Isolated pure compounds from column
chromatography.
2.3 Mechanistic investigation
After careful examination it was observed that at the same reaction condition silica itself
could not react with diol 14. On the other hand, on activated silica, no appreciable amount of
transformation was achieved in glacial acetic acid, and in sulfuric acid; only cholestenone 1 was
found to produce along with considerable amount of unreacted diol.27 The fact implied pꢀTsOH
to have some specific role, on the solid surface, towards producing 3 and 5. Whereas pꢀTsOH
(neat, without SiO2 or other medium, Table 2, entry 1) reacted with the diol at the same reaction
condition to produce only cholestenone 1 at 53% yield, a separate reaction with pꢀTsOH (60
mol%) along with catalytic amount of silica (50 mol %) induced the formation of 3 and 5 (by
TLC). On the other hand, separately in dichloromethane and ethanol, diol 14 was found to be
transformed quickly to furnish enone 1 only. These experiments proved a solid support to be an
essential medium to achieve the oneꢀpot transformation of the steroidal diol 14 into the enone 1,
endione 3 and dione 5. Herein, at this point it may be useful to mention that there are a number
of reports of different sorbents associated with pꢀTsOH for various useful transformative
methodologies.28
Applying the optimized reaction condition on cholestenone 1, it was found important to
isolate eneꢀdione 3 (37%) and dione 5 (32%). Thus it is indeed a twoꢀstep process to prepare 3
and 5 in better yields from the diol (via 1). But, when cholestenone 1 itself (without any medium
and other reagent) was heated at 120oC for 10 minute neither 3 nor 5 were found to be produced
which led us to discard the possibility of aerial oxidation of 1 into 3 and/ or 5. In addition, it is
interesting to mention that when we applied the same reaction condition on eneꢀdione 3 and
dione 5 seperately, no transformation was achieved at all. These results led us to conclude that 3
and 5 were formed only from 1 following two different pathways (Scheme 2). This fact was
made further convincing by examining the effect of some simple proton scavengers on the
reaction (Table 4, entries 1ꢀ2). This was attempted to reduce the yield of 1 first, which in turn
could yield 3 and 5 better if and only if these two were synthesized directly from diol 14 and not

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from 1. The idea was based on the fact that transformation of diol into cholestenone 1 was found
to be highly acid sensitive (acid transforms diol 14 rapidly into 1; also in solution phase and
neat) and could occur well in absence of silica. But addition of proton scavengers to the reaction
could not affect much the formation of 1 though the yield of 3 and 5 were found to be a little
lower. The results altogether thus led silica not to affect the formation of 1 from diol 14 (Fig. 2).
On the other hand, as the yield of 3 and 5 was not satisfactory as well (in comparison to 1), and
moreover, cholestenone 1 was transformed into 3 and 5 at the same reaction condition. The
results thus led to conclude, presumably, that in presence of SiO2/pꢀTsOH dual system, 3 and 5
were formed only from 1 and not from diol 14 (Scheme 2).
O
3
O
X
X
HO
O
OH
1
14
O
O
5
Scheme 2. Dienone 3 and dione 5 are formed from 1 following two different routes.
Table 4. Effect of proton scavengers along with pꢀTsOH on the solventꢀfree transformation of
4βꢀhydroxy cholesterol.a
Entry
Proton scavengerb
Yieldc (%)
1
3
5
4
5
6
7
1
2
DMAPd
Glycine
48
57
aAll the reactions were performed on 100 mg (0.248 mmol) of substrate (4βꢀhydroxy cholesterol) and 60
mol% of reagent (pꢀTsOH) and for 10 minutes in 120oC taking 1g (4g mmolꢀ1) of activated silica 60ꢀ120
b
as the solid support. For each reaction equimolar amount (to pꢀTsOH, i. e., 60 mol%) of proton
c
d
scavengers were employed. Isolated pure products by column chromatography. N, Nꢀdimethylꢀ4ꢀ
aminopyridine.

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Yamamoto et al., in their informative review flourished the concept of ‘designer acids’
through the combination of a Brønsted acid with a Lewis acid where one can synergistically
affect the other.29 As such acid combinations were found to produce satisfactory results in the
solution phases, and there is no report of any such designer acid working on the solid phase, we
thought to examine the concept in our solventꢀfree ketosteroid syntheses reactions. Thus, we
tried the transformation of diol 14 accomplished by pꢀTsOH/SiO2, separately in presence of
MgCl2, ZnCl2 and anhydrous FeCl3. But for the present solid supported transformation, the
‘designer acids’ concept was remained ineffective as the reactions conducted along with Lewis
acids produced almost comparable yield of the three products to the reactions that did not use
Lewis acids (Table 5, entry 1ꢀ3).
Table 5. Effect of Lewis acids along with pꢀTsOH on the solventꢀfree transformation of 4βꢀ
hydroxy cholesterol.a
Entry
Lewis acidb
Yieldc (%)
1
3
5
1
2
3
MgCl2. 6H2O
ZnCl2 (anh.)
FeCl3 (anh.)
48
55
52
7
7
8
10
7
10
aAll the reactions were performed on 100 mg (0.248 mmol) of substrate (4βꢀhydroxy cholesterol) and 60
mol% of reagent (pꢀTsOH) and for 10 minutes in 120oC taking 1g (4g mmolꢀ1) of activated silica 60ꢀ120
as the solid support. bFor each reaction equimolar amount (to pꢀTsOH, i. e., 60 mol%) of Lewis acids were
employed. cIsolated pure products by column chromatography.
There are a number of well enriched reviews describing the excellent scope of silica as a
reactionꢀpromoting component, and the usefulness is flourished, moreover through the
understanding of their mechanism of action.30 Opening of an S2R defect in silica with water
(Fig. 3a)30fꢀ30h as well as the cleavage of highly covalent SiꢀO bonds, either homolytically or
heterolytically, lead to the major physicochemical processes on silica surfaces.30hꢀ30k
Out of the various species generated in situ due to the breakage of SiꢀO bonds, silyl (both
Si +
Si
Si O
Si O
and
) and siloxy (both
and
) species owe to be the best suitable
surface sites in describing the mechanism for the present reaction (cationicꢀanionic cleavage is

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shown in Fig. 3b).30h,30i Thus we believe that the pathway for the formation of 3 and 5, from 1
utilizes the surface composing silyl cation countered with pꢀtoluenesulphonyl anion, and siloxy
anion countered with proton (the reaction medium is acidic!). And the modified composition
Si+ ꢀOTs
renders to be the better couple of solid support/acid possibly due to
, and as the other
combinations were ineffective, there exists a possibility of synergetic catalysis of pꢀTsOH with
SiO2 towards analyzing the products which were only due to the solid supports.
+
OH
OH2
H+
i) tautomerisation
ii) isomerisation
-H2O
HO
HO
O
O
H
1
H
14
1b
1a
Figure 2. Acidꢀcatalyzed transformation of 4βꢀhydroxycholesterol (14) into cholestꢀ4ꢀenꢀ3ꢀone, 1. Solid
silica probably does not affect the formation of 1.
OH
OH
O
O
+
H2O
(a)
(b)
O
+
Silyl cation
O-
O
Siloxy anion
Figure 3. (a) Opening of an S2R defect in silica with water. (b) One of the probable silica surface sites
= Si
due to cleavage. (
)
2.4 Application of the reaction protocol on different polyhydroxy steroids
The optimized reaction condition was then applied to other comparable steroidal biomolecules.
To generalize the reaction methodology the diꢀ/triꢀhydroxy steroids chosen were the 4βꢀhydroxy
derivatives of βꢀsitosterol (15) and 4β,7αꢀdihydroxy derivatives of cholesterol and βꢀsitosterol
(17 and 18 respectively).
When 4βꢀhydroxy βꢀsitosterol (15) was treated with 60 mol% of pꢀTsOH on activated
silica (60ꢀ120 mesh) at 120oC for 10 min, stigmastenone (2, 42%), stigmastꢀ4ꢀenꢀ3,6ꢀdione (16,
10%) and 5αꢀstigmastaneꢀ3,6ꢀdione (6, 8%) were isolated as pure products (Scheme 1). Of note,
in analogy to the results found with the diol, when the reaction was attempted with 4β,7αꢀ
dihydroxycholesterol (17) in solution taking dichloromethane as the solvent, cholestaꢀ4,6ꢀdienꢀ3ꢀ
one (11, 54%) was found to be the only product formed (this route is, thus, found easily useful to

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synthesize dienone 11 from cholesterol via triol 17). On the other hand, on solid silica, the same
reaction condition applied to this triol 17 furnished four different ketosteroids: i) cholestꢀ5ꢀenꢀ7ꢀ
one (19, 8%), ii) cholestaꢀ3,5ꢀdienꢀ7ꢀone (9, 13%), iii) cholestaꢀ4,6ꢀdienꢀ3ꢀone (11, 17%) and iv)
5αꢀcholestaneꢀ4,7ꢀdione (22, 7%). In the ketocholesterol series, the products, overall, thus led to
achieve interesting isomeric pairs, such as 9 and 11; 19 and 1; 22 and 5 (Schemes 1 and -3).
Accordingly, four ketoꢀfunctionalized derivatives of the phytosteroid βꢀsitosterol were isolated
by employing the reaction on 4β,7αꢀdihydroxy βꢀsitosterol (18): i) stigmastꢀ5ꢀenꢀ7ꢀone (20,
10%), ii) stigmastaꢀ3,5ꢀdienꢀ7ꢀone (10, 18%), iii) stigmastaꢀ4,6ꢀdienꢀ3ꢀone (21, 17%) and iv)
5αꢀstigmastaneꢀ4,7ꢀdione (23) (Scheme 3); but compound 23 could not be isolated in pure form.
It was obtained as a nonꢀseparable mixture with other enones and dienonones (by NMR).
However, like the cholesterol analogues, here also the isolated compounds correspond overall to
the interesting isomeric pairs in the ketoꢀβꢀsitosterol series, such as 20 and 2; 10 and 21; 23 and
6 (Schemes 1 and -3). In this context it is interesting to note that the reaction protocol, though in
general, furnished the oxosteroids both from the steroidal diols and triols, the reaction outcome is
different. In the same reaction condition, whereas the diols yield the corresponding oxoꢀ
derivatives by following only oxidation, the triols undergo simultaneous oxidation as well as
reduction (or, oxidative dehydration; e.g., 17 to 19) to result the corresponding oxosteroids, and
this difference in reactivity is attributed due to the 7αꢀhydroxy group in triol which renders an
additional dehydration site towards more possible intermediate/s suitable for reduction/ oxidative
dehydration.
R
R
R
R
R
p-TsOH/ SiO2
+
+
+
120OC, 5 min
HO
OH
O
O
O
O
H
OH
O
19; R= a
20; R= b
11; R= a
21; R= b
9; R= a
10; R= b
17; R= a
18; R= b
22; R= a
23; R= b
R: a=
,
b=
Scheme 3. Solid supportꢀdriven steroidal oxoꢀfunctionalization: pꢀTsOH/SiO2 on 4β,7αꢀdihydroxy
steroids. In solution phase (in dichloromethane) the triol 17 produced only 11 (54% isolated yield).

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3. Conclusion
In summary, a solid support/pꢀTsOHꢀcatalyzed milder, facile and greener transformative
procedure to yield ringꢀA and/or ringꢀB oxoꢀfunctionalized steroids has been accomplished.
Whereas in the solution phase, the diꢀ and trihydroxy steroids were found to result a single
product in each case, solid supports interestingly induced the formation of various other (but
selective) ketosteroids which altogether furnished a group of practically useful isomeric pairs in
the respective ketosteroid series. Detailed optimization of the reaction conditions along with the
modest experiments involving SiO2/pꢀTsOH dual system to understand the mechanism lead
presumably towards a possibility of a synergistic catalysis of pꢀTsOH with SiO2 for analyzing
the products which were only due to the solid supports.
4. Experimental
4.1 General
Melting points were measured in open capillary methods and were uncorrected. 1H NMR and 13C
NMR spectra were recorded on BruckerAvance 300MHz FTꢀNMR spectrometer using 5 mm
BBO probe. CDCl3 was used as solvent and TMS as reference material. Data are presented as
follows: chemical shift in ppm on the scale relative to δTMS = 0; coupling constant in J/Hz.
Infrared spectra were recorded either on Shimudzu FTꢀIR 8300 Spectrometer or Perkin Elmer
FTꢀIR Spectrometer Spectrum RX 1 as neat or thin films (KBr or Nujol) as indicated in the
experimental procedures, and at room temperature. Frequencies are given in wave numbers
(cmꢀ1). For column chromatography silica gel G, 60ꢀ120 mesh was used with petroleum etherꢀ
ethyl acetate mixture as the eluent. For thin layer chromatography (TLC), freshly made silica gel
plates (using silica gel for TLC + petroleum ether) were used and visualization was achieved by
staining with iodine.
4.2 General reaction of compounds 14, 15, 17 and 18 for the syntheses of the respective
ketosteroids
4βꢀHydroxycholesterol (14, 100 mg, 0.25 mmol) and a given amount of pꢀtoluenesulfonic acid
(please follow Table 1) were mixed homogenously with the preꢀactivated (150oC/1 mm Hg, 1h)
solid support (1g) in a dry mortar to dust by a pestle, transferred into a round bottomed flask (50
mL). The mixture was then heated in an oil bath at defined temperature for specific time. The

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reaction mixture was cooled, water (10 mL) was poured into it and the organic materials were
extracted in diethyl ether, washed with water (3× 15 mL) and the organic extract was dried
(Na2SO4) and the solvent was removed (vacuum). The residue was then subjected to silica gel
column chromatography to separate the products: cholestenone (1, from 5% ethyl acetate/ pet
ether, starting fractions), cholestꢀ4ꢀeneꢀ3,6ꢀdione (3, from 5% ethyl acetate/ pet ether, latter
fractions) and 5αꢀcholestaneꢀ3,6ꢀdione (5, from 8% ethyl acetate/ pet ether). General reaction
procedure of compounds 15, 17 and 18 to furnish the respective ketosteroids are completely
same with that of diol 14.
4.3 Product characterization
Cholestenone (1): Eluent in column chromatography: 5% ethyl acetate in petroleum ether.
1
Yield: traceꢀ58%. Pale yellow crystal. m.p. 78ꢀ79oC (methanol). H NMR (300 MHz, CDCl3): δ
0.71 (s, 3H, Meꢀ18), 0.85 (d, J=1.5 Hz, 3H, Meꢀ27), 0.88 (d, J=1.5 Hz, 3H, Meꢀ26), 0.91 (d,
J=6.6 Hz, 3H, Meꢀ21), 1.18 (s, 3H, Meꢀ19), 2.03 (dd, J=13.2 Hz and 3.3 Hz, 1H, Hꢀ2), 2.29ꢀ2.44
(m, 1H, Hꢀ2), 5.73 (s, 1H, Hꢀ4). 13C NMR: (75 MHz, CDCl3): δ 11.89 (CH3ꢀ18), 17.51(CH3ꢀ19),
18.65 (CH3ꢀ21), 21.00 (CH2ꢀ11), 22.56 (CH3ꢀ26), 22.83 (CH3ꢀ 27), 23.79 (CH2ꢀ15), 24.17 (CH2ꢀ
23), 28.00 (CH2ꢀ25) 28.17 (CH2ꢀ16), 32.02 (CH2ꢀ22), 32.95 (CH2ꢀ6), 35.58 (CH2ꢀ1), 35.66
(CH2ꢀ2), 35.74 (CHꢀ20), 36.06 (CHꢀ8), 38.58 (CH2ꢀ7), 39.47 (CH2ꢀ24), 39.47 (CH2ꢀ12), 39.59
(Cꢀ10), 42.36 (Cꢀ13), 53.78 (CHꢀ9), 55.84 (CHꢀ17), 56.06 (CHꢀ14), 123.71 (CHꢀ4), 171.80 (Cꢀ
5), 199.74 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 2345, 1684, 1654, 1618, 1560, 1508, 1377, 1266, 1227,
868.09, 722.
Cholest-4-en-3,6-dione (3): Eluent in column chromatography: 5% ethyl acetate in petroleum
1
ether. Yield: 5ꢀ13%. pale yellow crystal. m.p. 124ꢀ125oC (methanol). H NMR (300 MHz,
CDCl3): δ 0.72 (s, 3H, Meꢀ19), 0.86 (s, 3H, Meꢀ27), 0.88 (s, 3H, Meꢀ26), 0.93 (d, J=6.6Hz, 3H,
Meꢀ21), 1.17 (s, 3H, Meꢀ18), 2.49ꢀ2.55 (m, 3H, Hꢀ2 and Hꢀ7), 2.63 (dd, J=15.9Hz and 3.9Hz,
1H, Hꢀ2 or Hꢀ7), 6.17 (s, 1H, Hꢀ4). 13C NMR: (75 MHz, CDCl3): δ 11.89 (CH3ꢀ18), 17.51 (CH3ꢀ
19), 18.65 (CH3ꢀ21), 20.88 (CH2ꢀ11), 22.56 (CH3ꢀ26), 22.81 (CH3ꢀ 27), 23.79 (CH2ꢀ15), 23.97
(CH2ꢀ23), 28.01 (CH2ꢀ25) 28.01 (CH2ꢀ16), 33.98 (CH2ꢀ1), 34.22 (CH2ꢀ22), 35.54 (CH2ꢀ2), 35.68
(CHꢀ20), 36.06 (CHꢀ8), 39.14 (CH2ꢀ24), 39.46 (CH2ꢀ12), 39.82 (Cꢀ10), 42.54 (Cꢀ13), 46.83
(CH2ꢀ7), 50.99 (CHꢀ9), 55.96 (CHꢀ17), 56.56 (CHꢀ14), 125.45 (CHꢀ4), 161.11 (Cꢀ5), 199.55

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(CH2ꢀ6), 202.38 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 2345, 1686, 1654, 1560, 1542, 1508, 1376, 1222.
Analysis calcd: C, 81.35; H, 10.62. Found: C, 81.15; H, 10.82.
5α-Cholestane-3,6-dione (5): Eluent in column chromatography: 10% ethyl acetate in
petroleum ether. Yield: traceꢀ11%. pale yellow crystal. m.p. 170ꢀ173oC (acetone). 1H NMR (300
MHz, CDCl3): δ 0.69 (s, 3H, Meꢀ18), 0.86 (s, 3H, Meꢀ27), 0.88 (s, 3H, Meꢀ26), 0.92 (d,
J=6.3Hz, 3H, Meꢀ21), 0.96 (s, 3H, Meꢀ19), 2.30ꢀ2.50 (m, 5H, Hꢀ4, Hꢀ5, Hꢀ7), 2.54ꢀ2.61 (m, 2H,
Hꢀ2). 13C NMR: (75 MHz, CDCl3): δ 12.01 (CH3ꢀ18), 12.57 (CH3ꢀ19), 18.62 (CH3ꢀ21), 21.66
(CH2ꢀ11), 22.55 (CH3ꢀ26), 22.82 (CH3ꢀ 27), 23.79 (CH2ꢀ15), 23.99 (CH2ꢀ23), 28.00 (CH2ꢀ25)
28.00 (CH2ꢀ16), 35.68 (CHꢀ20), 36.04 (CH2ꢀ22), 37.00 (CH2ꢀ1), 37.40 (CH2ꢀ2), 38.03 (CHꢀ8),
38.08 (CHꢀ4), 39.35 (CH2ꢀ24), 39.44 (CH2ꢀ12), 41.26 (Cꢀ10), 42.99 (Cꢀ13), 46.63 (CH2ꢀ7),
53.43 (CHꢀ9), 56.07 (CHꢀ17), 56.66 (CHꢀ14), 57.49 (Cꢀ5), 209.27 (CH2ꢀ6), 211.44 (Cꢀ3). FTIR
(nujol, cmꢀ1): ν 1717, 1654, 1560, 1376. Analysis calcd: C, 80.94; H, 11.07. Found: C, 81.15; H,
11.17.
Stigmastenone (2): Eluent in column chromatography: 3% ethyl acetate in petroleum ether.
Yield: 42%. pale yellow crystal. m.p. 93ꢀ94oC (acetoneꢀmethanol).1H NMR (300 MHz, CDCl3):
δ 0.72 (s, 3H, Meꢀ18), 0.80 (s, 3H, Meꢀ27), 0.84 (d, J=6.3Hz, 3H, Meꢀ26), 0.87 (s, 3H, Meꢀ29),
0.92 (d, J=6.6 Hz, 3H, Meꢀ21),1.18 (s, 3H, Meꢀ19), 2.03 (dd, J=19.8 Hz and 3.3Hz, 1H, Hꢀ2),
2.29ꢀ2.47 (m, 1H, Hꢀ2), 5.73 (br s, 1H, Hꢀ4). 13C NMR: (75 MHz, CDCl3): δ 12.01 (CH3ꢀ18),
12.01 (CH3ꢀ29), 17.45 (CH3ꢀ26), 18.76 (CH3ꢀ21), 19.01 (CH3ꢀ19), 19.83 (CH3ꢀ 27), 21.11 (CH2ꢀ
11), 23.18 (CH2ꢀ28), 24.24 (CH2ꢀ15), 26.28 (CH2ꢀ25) 28.22 (CH2ꢀ16), 29.31 (CH2ꢀ23), 32.14
(CH2ꢀ2), 33.00 (CH2ꢀ6), 34.02 (CH2ꢀ22), 34.02 (CH2ꢀ7), 35.78 (CH2ꢀ1), 35.78 (CHꢀ8), 36.17
(CHꢀ20), 38.67 (Cꢀ10), 39.73 (CH2ꢀ12), 42.48 (Cꢀ13), 45.96 (CH2ꢀ24), 53.92 (CHꢀ9), 55.98
(CHꢀ17), 56.14 (CHꢀ14), 123.80 (CHꢀ4), 171.56 (Cꢀ5), 199.51 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 2345,
1683, 1618, 1560, 1542, 1508, 1377, 1267, 1227, 1186, 958, 866, 722.
Stigmast-4-en-3,6-dione (16): Eluent in column chromatography: 3% ethyl acetate in petroleum
1
ether. Yield: 10%. pale yellow crystal. m.p. 151ꢀ152oC (chloroformꢀmethanol). H NMR (300
MHz, CDCl3): δ 0.72 (s, 3H, Meꢀ18), 0.81 (s, 3H, Meꢀ27), 0.83 (s, 3H, Meꢀ26), 0.85 (s, 3H, Meꢀ
29), 0.94 (d, J=6.3Hz, 3H, Meꢀ21), 1.17 (s, 3H, Meꢀ19), 2.04 (d, J=3.0Hz, 1H, Hꢀ7), 2.47ꢀ2.55

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(m, 2H, Hꢀ2), 2.68 (dd, J=15.6Hz and 3.9Hz, 1H, Hꢀ7), 6.17 (br s, 1H, Hꢀ4). 13C NMR: (75
MHz, CDCl3): δ 11.88 (CH3ꢀ18), 11.96 (CH3ꢀ29), 17.50 (CH3ꢀ19), 18.69 (CH3ꢀ21), 18.99 (CH3ꢀ
26), 19.83 (CH3ꢀ 27), 20.85 (CH2ꢀ11), 23.02 (CH2ꢀ28), 23.96 (CH2ꢀ15), 25.95 (CH2ꢀ23), 28.01
(CH2ꢀ16), 29.07 (CH2ꢀ25), 33.79 (CH2ꢀ22), 33.97 (CH2ꢀ2), 34.19 (CHꢀ8), 35.50 (CH2ꢀ1), 36.03
(CHꢀ20), 39.09 (CH2ꢀ12), 39.82 (Cꢀ10), 42.51 (Cꢀ13), 45.75 (CH2ꢀ24), 46.83 (CH2ꢀ7), 50.94
(CHꢀ9), 55.80 (CHꢀ17), 56.51 (CHꢀ14), 125.44 (CHꢀ4), 161.12 (Cꢀ5), 199.61 (Cꢀ3), 202.46
(CH2ꢀ6). FTIR (nujol, cmꢀ1): ν 2345, 1686, 1654, 1618, 1560, 1542, 1508, 1376, 1222. Analysis
calcd: C, 81.63; H, 10.87. Found: C, 81.41; H, 10.62.
5α-Stigmastane-3,6-dione (6): Eluent in column chromatography: 8% ethyl acetate in
petroleum ether. Yield: 8%. pale yellow crystal. m.p. 192ꢀ194oC (acetone). 1H NMR (300 MHz,
CDCl3): δ 0.69 (s, 3H, Meꢀ18), 0.81 (s, 3H, Meꢀ27), 0.83 (s, 3H, Meꢀ29), 0.85 ( s, 3H, Meꢀ26),
0.93 (d, J=6.3Hz, 3H, Meꢀ21), 0.96 (s, 3H, Meꢀ19), 2.25ꢀ2.45 (m, 5H, Hꢀ4, Hꢀ5, Hꢀ7), 2.54ꢀ2.61
13
(m, 2H, Hꢀ2). C NMR: (75 MHz, CDCl3): δ 11.96 (CH3ꢀ18), 12.01 (CH3ꢀ29), 12.56 (CH3ꢀ19),
18.66 (CH3ꢀ21), 18.99 (CH3ꢀ26), 19.83 (CH3ꢀ 27), 21.66 (CH2ꢀ11), 23.02 (CH2ꢀ28), 24.00 (CH2ꢀ
15), 25.96 (CH2ꢀ23), 28.05 (CH2ꢀ16), 29.06 (CH2ꢀ25) 33.78 (CH2ꢀ22), 36.04 (CHꢀ20), 37.00
(CHꢀ4), 37.40 (CH2ꢀ2), 38.03 (CHꢀ8), 38.08 (CH2ꢀ1), 39.34 (CH2ꢀ12), 41.27 (Cꢀ10), 42.99 (Cꢀ
13), 45.75 (CH2ꢀ24), 46.63 (CH2ꢀ7), 53.43 (CHꢀ9), 55.97 (CHꢀ17), 56.58 (CHꢀ14), 57.50 (Cꢀ5),
209.28 (CH2ꢀ6), 211.47 (Cꢀ3). FTIR (nujol, cmꢀ1): ν 1707, 1685, 1618, 1560, 1542, 1508, 1377,
1260, 1239. Analysis calcd: C, 81.25; H, 11. 29. Found: C, 81.05; H, 11.02.
Cholest-5-en-7-one (19): Eluent in column chromatography: 2% ethyl acetate in petroleum
ether. Yield: 8%. pale yellow gum. 1H NMR (300 MHz, CDCl3): δ 0.71 (s, 3H, Meꢀ19), 0.72 (d,
J=7.2 Hz, 3H, Meꢀ27), 0.82 (d, J=6.3 Hz, 3H, Meꢀ26), 0.91(d, J=6.6 Hz, 3H, Meꢀ21), 1.13 (s,
3H, Meꢀ18), 3.08 (d, J=7.2 Hz, 1H, Hꢀ8), 6.07 (s, 1H, Hꢀ6). 13C NMR (75 MHz, CDCl3): δ
11.97, 17.15, 18.68, 20.99, 22.56, 22.82, 23.09, 23.83, 24.24, 28.02, 28.21, 31.05, 31.81, 34.68,
35.23, 35.77, 36.15, 37.80, 39.52, 39.72, 42.38, 54.27, 56.03, 56.17, 140.46, 141.13, 193.67.
FTIR (nujol, cmꢀ1): ν 1684.
Cholesta-3,5-dien-7-one (9): Eluent in column chromatography: 2% ethyl acetate in petroleum
ether. Yield: 13%. pale yellow crystal. m.p. 112ꢀ114oC (ethanol).1H NMR (300 MHz, CDCl3): δ

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0.69 (s, 3H, Meꢀ18), 0.86 (s, 3H, Meꢀ27), 0.88 (s, 3H, Meꢀ26), 0.92 (d, J=6.6 Hz, 3H, Meꢀ21),
1.09 (s, 3H, Meꢀ19), 6.11 (dd, J=9.9 Hz and 3.0 Hz, 1H, Hꢀ4), 6.80 (q, J=2.4 Hz, Hꢀ6) (for 19
13
Me), 6.89 (ddd, J=10.2 Hz, 6.3 z and 2.4 Hz, 1H, Hꢀ3). C NMR (75 MHz, CDCl3): δ 11.92,
18.75, 21.04, 21.41, 22.57, 22.82, 23.85, 24.17, 28.03, 28.19, 31.26, 31.93, 35.77, 38.62, 36.19,
39.32, 39.53, 39.58, 42.39, 49.44, 56.15, 56.56, 129.19, 134.81, 141.74, 147.63, 188.48. FTIR
(nujol, cmꢀ1): ν 1677, 1635, 1619, 1560, 1542, 1377, 1301, 1265, 1150, 1078, 1021, 960, 891,
849, 815, 723, 670. Analysis calcd: C, 84.75; H, 11.06. Found: C, 84.55; H, 11.22.
Cholesta-4,6-diene-3-one (11): Eluent in column chromatography: 5% ethyl acetate in
petroleum ether. Yield: 17%. pale yellow crystal, m.p. 80ꢀ81oC (methanol). 1H NMR (300 MHz,
CDCl3): δ 0.76 (s, 3H, Meꢀ18), 0.86 (d, J=1.2 Hz, 3H, Meꢀ26), 0.89 (d, J=1.2 Hz, 3H, Meꢀ29),
0.93 (d, J=6.6 Hz, 3H, Meꢀ21), 1.12 (s, 3H, Meꢀ19), 5.67 (s, 1H, Hꢀ4), 6.12 (ddd, J= 1.8 Hz, 18
Hz and 9.9 Hz, 2H, Hꢀ6 and Hꢀ7). 13C NMR (75 MHz, CDCl3): δ 11.93, 16.32, 18.70, 20.74,
22.56, 22.80, 23.77, 23.90, 28.03, 28.18, 34.00 (2), 35.81, 36.14, 36.19, 37.83, 39.54, 39.65,
43.49, 50.80, 53.53, 56.14, 123.55, 127.82, 141.56, 164.01, 199.55. FTIR (nujol, cmꢀ1): ν 1688.
Analysis calcd: C, 84.75; H, 11.06. Found: C, 84.65; H, 10.92.
Cholest-4,7-dione (22): Eluent in column chromatography: 5% ethyl acetate in petroleum ether.
1
Yield: 7%. pale yellow crystal, m.p. 144ꢀ146oC (chloroformꢀmethanol). H NMR (300 MHz,
CDCl3): δ 0.66 (s, 3H, Meꢀ18), 0.85 (d, J=1.2 Hz, 3H, Meꢀ27), 0.87 (d, J= 1.2 Hz, 3H, Meꢀ26),
13
0.91 (d, J=6.3 Hz, 3H, Meꢀ21), 1.01 (s, 3H, Meꢀ19), 2.25ꢀ2.35 (m, 3H), 2.52ꢀ2.54 (m, 1H). C
NMR (75 MHz, CDCl3): δ 12.09, 13.21, 18.81, 22.05, 22.80, 22.56, 23.81, 24.89, 28.02, 28.40,
29.71, 35.65, 36.17, 37.17, 38.74, 38.94, 39.49, 40.95, 42.44, 42.79, 48.86, 49.56, 55.12, 55.95,
59.89, 209.58, 212.52. FTIR (nujol, cmꢀ1): ν 1719, 1705, 1653, 1376, 1270, 1154, 751, 721, 667.
Analysis calcd: C, 80.94; H, 11.07. Found: C, 85.11; H, 11.02.
Stigmast-5-en-7-one (20): Eluent in column chromatography: 2% ethyl acetate in petroleum
ether. Yield: 10%. pale yellow gum. 1H NMR (300 MHz, CDCl3): δ 0.71 (s, 3H, Meꢀ18), 0.80 (s,
3H, Meꢀ27), 0.84 (d, J=6.3 Hz, 3H, Meꢀ26), 0.87(s, 3H, Meꢀ29), 0.92 (d, J=6.3 Hz, 3H, Meꢀ21),
1.17 (s, 3H, Meꢀ19), 6.07 (s, 1H, Hꢀ6). 13C NMR (75 MHz, CDCl3): δ 11.99, 17.16, 18.75,
19.06, 19.83, 21.00, 23.12, 24.25, 26.15, 28.24, 29.22, 29.71, 31.07, 31.82, 33.94, 34.69, 35.26,

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37.81, 36.15, 39.73, 42.40, 45.89, 54.28, 56.04, 140.46, 141.14, 193.66. FTIR (nujol, cmꢀ1): ν
1686. Analysis calcd: C, 84.40; H, 11.72. Found: C, 84.64; H, 11.82.
Stigmasta-3,5-diene-7-one (10): Eluent in column chromatography: 2% ethyl acetate in
petroleum ether. Yield: 18%. pale yellow solid, m.p. 122oC. 1H NMR (300 MHz, CDCl3): δ 0.70
(s, 3H, Meꢀ18), 0.79 (s, 3H, Meꢀ27), 0.84 (d, J=6.6 Hz, 3H, Meꢀ26), 0.88 (s, 3H, Meꢀ29), 0.94
(d, J=6.6 Hz, 3H, Meꢀ21), 1.09 (s, 3H, Meꢀ19), 2.06 (dt, J=6.0 Hz and 3.3 Hz, 1H, Hꢀ2),2. 32 (t,
J= 5.4 Hz, 1H, Hꢀ8), 2.45 (dd, J= 19.8 Hz and 6.3 Hz, 1H, Hꢀ2), 6.11 (dd, J=9.9 Hz and 2.7 Hz,
1H, Hꢀ4), 6.80 (q, J=2.7 Hz, 1H, Hꢀ6) (for 19 Me), 6.88 (ddd, J=9.9 Hz, 6.3 Hz and 2.4 Hz, 1H,
Hꢀ3). 13C NMR (75 MHz, CDCl3): δ 11.92, 12.01, 18.81, 19.07, 19.83, 21.04, 21.40, 23.13,
24.18, 26.17, 28.21, 29.22, 31.26, 31.93, 33.98, 36.14, 38.62, 39.32, 39.58, 42.39, 45.90, 49.44,
56.06, 56.56, 129.19, 134.81, 141.74, 147.63, 188.47. FTIR (nujol, cmꢀ1): ν 1670, 1654, 1630,
1617, 1560, 1377, 1274, 1155, 960, 783, 722. Analysis calcd: C, 84.81; H, 11.29. Found: C,
84.65; H, 11.02.
Stigmasta-4,6-diene-3-one (21): Eluent in column chromatography: 5% ethyl acetate in
petroleum ether. Yield: 17%. pale yellow crystal, m.p. 66ꢀ70oC (methanol). 1H NMR (300 MHz,
CDCl3): δ 0.76 (s, 3H, Meꢀ18), 0.82 (d, J=6.3 Hz, 3H, Meꢀ26), 0.87 (d, J=7.2 Hz, 3H, Meꢀ29),
0.93 (d, J=6.3 Hz, 3H, Meꢀ21), 1.11 (s, 3H, Meꢀ19), 5.66 (s, 1H, Hꢀ4), 6.12 (ddd, J= 1.8 Hz, 18
Hz and 9.1 Hz, 2H, Hꢀ6 and Hꢀ7). 13C NMR (75 MHz, CDCl3): δ 11.92, 12.01, 16.32, 18.75,
19.08, 19.83, 20.72, 23.14, 23.77, 27.12, 28.21, 29.26, 29.53, 33.98, 33.98, 36.13, 37.14, 37.81,
39.62, 43.47, 50.77, 45.92, 53.51, 56.02, 123.53, 127.80, 141.61, 164.06, 199.63. FTIR (nujol,
cmꢀ1): ν 1687. Analysis calcd: C, 84.81; H, 11.29. Found: C, 84.55; H, 11.09.
5α-Stigmastane-4,7-dione (23, as mixture): Eluent in column chromatography: 5% ethyl acetate
in petroleum ether. From NMR spectral data of the nonꢀseperable mixture of the titled compound
with other enones and dienones, only the values correspond to 5αꢀstigmastaneꢀ4,7ꢀdione
(obtained with the help of the spectral values of the corresponding pure 5αꢀcholestaneꢀ4,7ꢀdione,
22) are produced here. The δ values, especially for 13C, as collected from a mixture of a number
of peaks, may be little bit different for the actual pure compound. 1H NMR (300 MHz, CDCl3): δ
0.66 (s, 3H, Meꢀ18), 0.84 (d, J=6.0 Hz, 3H, Meꢀ27), 0.88 (d, J= 2.7 Hz, 3H, Meꢀ26), 0.92 (d,

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13
J=6.3 Hz, 3H, Meꢀ21), 1.01 (s, 3H, Meꢀ19). C NMR (75 MHz, CDCl3): δ 11.94, 12.01, 13.20,
14.10, 18.8, 21.83, 22.53, 22.70, 23.15, 24.91, 28.21, 28.42, 36.14, 37.19, 38.75, 38.95, 39.59,
40.94, 42.44, 42.79, 45.45, 48.88, 49.40, 49.60, 55.04, 55.96, 59.91, 209.54, 212.50.
Acknowledgements
The authors are thankful to the University of North Bengal, Darjeeling for providing all
the facilities. AS and JD are thankful to UGC, New Delhi and CSIR, New Delhi
respectively for providing their fellowships.
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Table of Contents
A milder, facile and greener transformative protocol, specific on solid supports, to yield ring-A
and/or ring-B oxo-functionalized steroids has been accomplished.