Expedited Baeyer-Villiger oxidation of steroidal ketones by microwave irradiation

Article abstract of DOI:10.1016/j.steroids.2011.06.014

Microwave (MW) assisted reactions are currently having considerable importance in the synthesis of organic compounds. Considering the remarkable application of Baeyer-Villiger (BV) reaction in the synthesis of natural products and steroid-peptide conjugates, we report here some of our findings of BV oxidation of carbonyl compounds with special reference to steroidal ketones under MW irradiation justifying its accelerating effect.

Full text of DOI:10.1016/j.steroids.2011.06.014

Steroids 76 (2011) 1341–1345
Contents lists available at ScienceDirect
Steroids
journal homepage: www.elsevier.com/locate/steroids
Expedited Baeyer–Villiger oxidation of steroidal ketones by microwave irradiation
⇑
Juri Moni Borah, Pritish Chowdhury
Natural Products Chemistry Division, North East Institute of Science & Technology, CSIR, Jorhat 785 006, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 April 2011
Received in revised form 27 June 2011
Accepted 30 June 2011
Available online 13 July 2011
Microwave (MW) assisted reactions are currently having considerable importance in the synthesis of
organic compounds. Considering the remarkable application of Baeyer–Villiger (BV) reaction in the
synthesis of natural products and steroid–peptide conjugates, we report here some of our findings of
BV oxidation of carbonyl compounds with special reference to steroidal ketones under MW irradiation
justifying its accelerating effect.
Ó 2011 Elsevier Inc. All rights reserved.
Keywords:
Steroidal ketones
Baeyer–Villiger reaction
Microwave irradiation
Lactonization
Esterification
1. Introduction
in dark for completion. Sometimes reaction gave a mixture of prod-
ucts because of the incomplete oxidation at both the sites of the
The Baeyer–Villiger (BV) oxidation is an important reaction in
organic synthesis which leads to the conversion of acylic ketones
into esters and cyclic ketones into lactones [1]. Diverse experimen-
tal and theoretical studies aiming to know insights on the mecha-
nistic details of this reaction have been well documented in
chemical literature [2–10] in recent times. In fact the reaction finds
a remarkable application on the synthesis of natural product
compounds and their analogs [2,5]. In the steroid field the role of
BV reaction for converting 20-oxopregnanes to 17-acetoxysteroids
of potent sex hormones [11], and also of the formation of the bio-
logically active steroidal D-ring lactones are well documented in
literature [12–17]. This in conjugation with our interest on steroid
transformations [18–23], we initiated the work on the develop-
ment of steroid–peptide conjugates which are currently gaining
importance because of their potent biological importance as syn-
thetic receptors of oligopeptide sequences [24], as protease-like
artificial enzymes [25] and as mimics of natural cationic peptide
antibiotics [26]. Thus in connection with that work on a steroid–
peptide conjugate synthesis, we did require to perform BV oxida-
carbonyl groups of the compound 1 simultaneously, which drew
our attention towards the application of MW irradiation in BV
oxidation of the compound. Moreover reaction time did not get
reduced when reactions were performed on refluxing chloroform,
rather they became messy giving number of products.
The most fundamental obstacles in developing technologies are
to minimize the energy consumption and to eliminate/minimize
the use of hazardous substances. In this scenario, use of microwave
energy to bring about chemical transformations is a suitable alter-
native, as it takes care of two very essential criteria of synthesis:
minimize energy consumption required for heating and time
required for the reaction [30]. Therefore, currently studies on the
effect of MW irradiation in organic and macromolecular chemistry
are a subject of considerable interest [31,32]. Accelerating effect
and efficient non-contact heating are some of the traits of MW irra-
diated reactions. Recently Carsten et al. [33], in their work on poly-
mer chemistry, demonstrated the accelerating effect of MW
irradiation through the facile synthesis of two higher lactones,
viz., 1-oxa-2-oxocyclooctanone and 1-oxo-2-oxacyclononanone
via BV reaction of their corresponding ketone precursors. This
has led us to hit upon the idea of applying MW technology in BV
oxidation of compound 1 to get the desired steroidal ring-A
lactone.
tion as the key step on the compound 5a-pregnan-3,17-dione 1,
to get a seco-steroidal building block via its lactonization and sub-
sequent ring opening to seco-steroidal hydroxysteroids to incorpo-
rate a peptide bond with it. Usual BV oxidation of the compound 1
with m-CPBA or perbenzoic acid in presence or in absence of a cat-
alyst like CAN [27], H2SO4 [28], TFA [29] took much longer time
and many times the reaction mixture had to be kept for 2–3 weeks
Thus when the compound 1 was subjected to BV oxidation
under MW irradiation at 350W, in chloroform, it furnished the
oxidized products 3-oxa-4-oxo-4a-homo lactone 1a (60%) and 3-
oxo-4-oxa-4a-homo lactone 1b (40%) in a very clean and fast
reaction. Obviously oxidation occurred simultaneously at the sites
⇑
Corresponding author. Tel.: +91 376 2370 121x2362; fax: +91 376 2370 011.
E-mail address: pritishchowdhury@yahoo.com (P. Chowdhury).
of both the carbonyl groups of the compound 5a-pregnan-3,
0039-128X/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.steroids.2011.06.014

1342
J.M. Borah, P. Chowdhury / Steroids 76 (2011) 1341–1345
O
OAc
OAc
BV,MW
O
+
O
O
H
O
H
O
H
1b
1
1a
O
OAc
OAc
+
O
O
O
O
H
H
H
O
Scheme 1. Baeyer–Villiger reaction of 5a-pregnan-3,17-dione.
17-dione 1. Recently, Riveria et al. [34] have reported regioselectiv-
ity of conventional BV reaction of 3-ketosteroids on the basis of the
conformational effects due to favorable formation of Criegee
intermediate and reported the formation of 3-oxa-4-oxo-4a-homo
lactone regioselectively from 3-keto-spirostanes and some other
(t), quartet (q) and multiplet (m). Mass spectrometric analysis
was performed by positive mode electro spray ionization with Bru-
ker Esquire 3000 LC-MS instrument. Elemental analysis was car-
ried out in Varian CHN analyzer.
3-ketosteroids of 5a-series where as in case of 5b-series both
2.2. Microwave instrumentation
3-oxa-4-oxo-4a-homolactone and 3-oxo-4-oxa-4a-homolactone
are obtained in almost 1:1 ratio. However in the present case we
isolated both 3-oxa-4-oxo-4a-homo lactone 1a and 3-oxo-4-oxa-
4a-homo lactone 1b in the ratio of 3:2 under MW irradiation
All MW reactions were carried out in a Synthos 3000 (Anton
Paar) microwave reactor. The multitude microwave has a twin
magnetron (2.45 GHz) with maximum output power of 1400 W.
The output power can be controlled in unpulsed control mode over
whole power range which is adjustable in 1 W increments. A Moto-
rola 68xxx series microprocessor system control is used to mea-
sure temperature, pressure, time and power during the reaction.
The temperature and pressure were monitored throughout the
reaction by an infrared detector. The temperature can be measured
from 0 to 280 °C with uncertainty 1%. The pressure can be mea-
sured from 0 to 86 bar with uncertainty 0.2 bar
condition from the compound 1 of 5a-series (Scheme 1).
In a typical reaction, 500 mg of the compound 1 furnished
357 mg (65%) of the mixture of the oxidized products 1a and 1b
which were further purified by preparative TLC (Pet.ether: EtOAc::
8:1) giving 214 mg of 1a and 142 mg of 1b.
In the next step, we tried to generalize the reaction by extend-
ing the reaction to a number of steroidal ketones 2–12 and to some
non-steroidal ketones 13–14 (Table 1).
During the investigation we also found that for the cases (sub-
strates 7–10 and 12) the oxidation furnished only one isomer viz.,
7a–10a and 12a as confirmed by TLC as well as analytical and spec-
tral data. The advantages of MW assisted BV reactions over the
conventional BV oxidation methods are depicted in the (Table 2).
In conclusion, we report here the development of MW pro-
moted BV oxidation reaction of several steroidal ketones as well
as a few non-steroidal carbonyl compounds. The method would
definitely find a significant place in organic synthesis promoting
green technology. The reaction proceeds without the aid of any
catalysts, requires very short duration of time giving high yield
of oxidized products.
2.3. Typical procedure for the Baeyer–Villiger oxidation
2.3.1. Under MW irradiation
A mixture of m-CPBA (0.66 g, 3.9 mmol) and 5a-pregnan-3,
17-dione (1.5 mmol) in CHCl3 (10 ml) were irradiated in a closed
vessel in a Synthon 3000 microwave reactor at 350 W, 105 °C
and 7.1 bar for 5 min. The reaction mixture was then allowed to
cool to room temperature and washed subsequently with 10%
Na2SO3 (2 Â 100 ml) and aq. 10% NaHCO3 (2 Â 100 ml). The organic
phase was dried over anhydrous Na2SO4 and evaporated under re-
duced pressure which was further purified by column chromatog-
raphy over silica gel using 1:10 ethyl acetate–hexane as the eluent
to furnish the pure lactones 17b-acetoxy-3-oxa-A-homo-5a-
2. Experimental
androstan-4-one (1a) and 17b-acetoxy-4-oxa-A-homo-5
a-andro-
stan-3-one (1b).
2.1. General methods
Melting points were measured with a Buchi B-540 melting
point apparatus and are uncorrected. All the chemicals used were
of reagent grade of E. Merck and were used without further purifi-
cation. The progress of each of the reaction was monitored on
Merck thin layer chromatography silica gel 60 F254. IR spectra were
recorded with a Perkin-Elmer model 2000 series FT-IR spectrome-
ter for solutions in chloroform. Infrared absorbance is reported in
reciprocal centimeters (cmÀ1). 1H and 13C NMR spectra were
recorded on a Bruker DPX (300 MHz) spectrometer using CDCl3
or DMSO-d6 as solvent with tetramethylsilane (TMS) as internal
standard on ppm scale (d). Multiplicity of the resonance peaks
are indicated as singlet (s), broad singlet (bs), doublet (d), triplet
2.3.2. By classical
A solution of m-CPBA (0.66 g, 3.9 mmol) in 5 ml CH2Cl2 was
added to a stirred solution of 5 -pregnan-3,17-dione (1.5 mmol)
a
in CH2Cl2 (10 ml) at 0 °C in presence of catalytic amount of trifluoro
acetic acid under air. The reaction mixture was stirred at room
temperature for three weeks as required for disappearance of the
starting material, vide TLC. After usual work up the reactions were
checked by TLC and formation of several products were shown on
TLC. The crude was purified by preparative TLC using ethyl
acetate–hexane (1:8) as the eluent to furnish the pure lactones
17b-acetoxy-3-oxa-A-homo-5
acetoxy-4-oxa-A-homo-5 - androstan-3-one (1b).
a-androstan-4-one (1a) and 17b-
a

J.M. Borah, P. Chowdhury / Steroids 76 (2011) 1341–1345
1343
Table 1
MW assisted BV oxidation of carbonyl compounds with peracids.
SI. no
1
Substrates
Products
SI. no
8
Substrates
Products
1
1a + 1b
O
O
O
O
AcO
AcO
H
H
8a
8
2
9
O
O
O
O
+
O
H
2a
O
H
2b
Cl
O
H
H
9ab
Cl
H
2
9
3
10
OAc
O
O
O
O
HO
AcO
AcO
H
10a
H
3a
HO
H
3
H
10
4
5
6
11
12
13
OAc
O
OAc
O
AcO
AcO
H
4a
O
11a
H
4
11
OAc
OAc
C8H17
C8H17
O
Cl
O
O
Cl
H
H
H
H
O
12a
12
5ab
5
O
O
O
O
13
HO
13a
H
6a
HO
H
6
7
14
O
O
O
O
CH3
O
CH3
O
14a
H
7a
14
H
7
(a) Yields refer to the isolated products which were fully characterized by spectral analysis.
(b) The compounds have shown two molecular ion peaks due to 35Cl and 37Cl.
2.4. 17b-Acetoxy-3-oxa-A-homo-5
a
-androstan-4-one (1a) and 17b-
34.5 (C-12); 40.5 (C-13); 51.4 (C-14); 30.7 (C-15); 26.9 (C-16);
79.8 (C-17); 171.9 (C-Oac). IR (CHCl3): 1735, 1400, 1250, 950
cmÀ1; MS (m/z): 348 (M+). Anal. Calcd. for C21H32O4: C, 72.38; H,
9.26. Found: C, 72.32; H, 9.22.
acetoxy-4-oxa-A-homo-5 -androstan-3-one (1b)
a
Regioisomeric mixture (⁄signals corresponding to the 3-oxa 4-
oxo-4a-homo-lactone): 1H NMR (300 MHz, CDCl3): 0.66 (s, 3H,
Me); 0.89 (d, 3H, J = 8.4 Hz); 1.1⁄, 1.3 (s, 3H, Me); (0.7–1.1, m,
2.5. 3-Oxa-A-homo-5a-cholestan-4-one (2a) and 4-Oxa-A-homo-5a-
cholestan-3-one (2b)
12H); 2.01 (s, 3H, OAc); 3.68⁄ (d, 1H, J = 12.9 Hz, H-2
a); 4.15–
4.17 (m, 1H, H-4aa); 4.25–4.29 (overlapping signal, m 2H, H-4ab
and H-17); 4.56–4.61⁄ (m, 1H, H-2b); 13C NMR (CDCl3): d = 36.2
(C-1); 63.3 (C-2); 176.3, 176.4⁄ (C-3); 35.6 (C-4); 36.8 (C-5); 24.4
(C-6); 25.7 (C-7); 29.8 (C-8); 42.6 (C-9); 37.8 (C-10); 20.9 (C-11),
Regioisomeric mixture (⁄signals corresponding to the 3-oxa
4-oxo-4a-homo-lactone) 1H NMR (300 MHz, CDCl3): 0.66 (s, 3H,
Me); 0.89 (d, 3H, J = 8.4 Hz); 1.1⁄, 1.3 (s, 3H, Me); 0.7–2.1 (m,

1344
J.M. Borah, P. Chowdhury / Steroids 76 (2011) 1341–1345
Table 2
Comparision between MW assisted and Classical BV reactions.
Substrate
Products
Mw assisted reaction
Yield (%)
Classical reaction
Yield (%)
Time required (min)
Time required
1
2
3
4
5
6
7
8
1a + 1b
2a + 2b
3a
4a
5a
6a
7a
8a
9a
10a
11a
12a
13a
14a
65
67
73
75
76
69
72
75
79
80
71
78
56
67
5
5
3
3
3
3
4
4
4
4
2
4
4
3
20
35
53
49
51
54
48
45
49
47
43
49
40
43
3 weeks
3 weeks
7 days
7 days
7 days
7 days
15 days
15 days
15 days
15 days
9 days
15 days
12 h
9
10
11
12
13
14
12 h
35-H); 3.88⁄ (d, 1H, J = 13.2 Hz, H-2
a
); 4.0–4.1 (m, 1H, H-4a
a
); 4.2–
2.9. 17b-Acetoxy-3b-hydroxy-5a-Androstane (6a)
4.25 (m, 1H, H-4ab); 4.61–4.68⁄ (m, 1H, H-2b); 13C NMR (CDCl3):
d = 36.2 (C-1); 63.3 (C-2); 176.3, 176.4⁄ (C-3); 35.6 (C-4); 36.8 (C-
5); 24.4 (C-6); 25.7 (C-7); 29.8 (C-8); 42.6 (C-9); 37.8 (C-10);
20.9 (C-11); 34.5 (C-12); 40.5 (C-13); 51.4 (C-14); 30.7 (C-15);
26.9 (C-16); 43.9 (C-17); 18.7 (C-18); 15.4 (C-19); 39.1 (C-20);
15.8 (C-21); 35.7 (C-22); 24.6 (C-23); 39.7 (C-24); 28.3 (C-25);
Melting point (m.p.) 143–146 °C; 1H NMR (300 MHz, CDCl3):
0.70 (s, 3H); 1.1 (s, 3H); 0.7–2.0 (m, 23H, CH&CH2); 2.0 (s, 3H);
4.1 (m, 1H); 4.5 (m, 1H); 13C NMR (CDCl3): d = 36.2 (C-1); 28.2
(C-2); 72.9 (C-3); 33.1 (C-4); 40.9 (C-4); 27.2 (C-6); 31.7 (C-7);
37.1 (C-8); 56.9 (C-9); 36.5 (C-10); 19.8 (C-11); 38.2 (C-12); 41.3
(C-13); 53.5 (C-14); 20.9 (C-15); 31.1 (C-16); 84.2 (C-17); 171.3
(C–OCOCH3); 17.2 (C–CH3COO). IR (CHCl3): 3300, 1730, 1400,
1250, 950 cmÀ1; MS (m/z): 334 (M+). Anal. Calcd. for C21H34O3: C,
75.41; H, 10.25. Found: C, 75.40; H, 10.23.
22.6 (C-26); 22.8 (C-27). IR (CHCl3): 1735, 1400, 1250, 950 cmÀ1
;
MS (m/z): 402 (M+). Anal. Calcd. for C27H46O2: C, 80.54; H, 11.51.
Found: C, 80.51; H, 11.48.
2.6. 3b,17b-Diacetoxy-5a-Androstane (3a)
2.10. 17-Oxa-5a-Androstan-16-one (7a)
Melting point (m.p.) 126–128 °C; 1H NMR (300 MHz, CDCl3): 0.70
(s, 3H); 0.7–1.9 (m, 22H, CH&CH2); 1.1 (s, 3H); 2.0 (s, 6H); 4.5 (m,
2H); 13C NMR (CDCl3): d = 36.2 (C-1); 28.2 (C-2); 75.3 (C-3); 172.3
(C–OCOCH3); 33.1 (C-4); 40.9 (C-4); 27.2 (C-6); 31.7 (C-7); 37.1 (C-
8); 56.9 (C-9); 36.5 (C-10); 19.8 (C-11); 38.2 (C-2); 41.3 (C-13);
53.5 (C-14); 20.9 (C-15); 31.1 (C-16); 84.2 (C-17); 17.2 (C–CH3COO).
IR (CHCl3): 1735, 1400, 1250, 950 cmÀ1; MS (m/z): 376 (M+). Anal.
Calcd. for C23H36O4: C, 73.37; H, 9.64. Found: C, 73.34; H, 9.61.
Melting point (m.p.) 109–111 °C; 1H NMR (300 MHz, CDCl3): 0.9
(s, 3H); 1.1 (s, 3H); 0.9–1.9 (m, 22H, CH&CH2); 2.2 (m, 2H); 13C NMR
(CDCl3): d = 34.2 (C-1); 28.2 (C-2); 22.9 (C-3); 33.1 (C-4); 40.9 (C-4);
27.2 (C-6); 31.7 (C-7); 37.1 (C-8); 56.9 (C-9); 36.5 (C-10); 19.8 (C-
11); 38.2 (C-12); 74.3 (C-13); 53.5 (C-14); 35.9 (C-15); 43.1 (C-16);
175.2 (C-17); 171.3 (C–OCOCH3); 17.2 (C–CH3COO). IR (CHCl3):
1721, 1400, 1250, 950 cmÀ1; MS (m/z): 290 (M+). Anal. Calcd. for
C19H30O2: C, 78.57; H, 10.41. Found: C, 78.54; H, 10.38.
2.7. 5a-Androstan-17b-acetate (4a)
Melting point (m.p.) 78–80 °C; 1H NMR (300 MHz, CDCl3): 0.70
(s, 3H), 0.7–2.0 (m, 24H, CH&CH2); 1.1 (s, 3H); 2.1 (s, 3H); 4.5 (m,
1H); 13C NMR (CDCl3): d = 36.2 (C-1); 28.2 (C-2); 25.9 (C-3); 33.1
(C-4); 40.9 (C-4); 27.2 (C-6); 31.7 (C-7); 37.1 (C-8); 56.9 (C-9);
36.5 (C-10); 19.8 (C-11); 38.2 (C-12); 41.3 (C-13); 53.5 (C-14);
20.9 (C-15); 31.1 (C-16); 84.2 (C-17); 171.3 (C–OCOCH3). 17.2
(C–CH3COO). IR (CHCl3): 1732, 1400, 1250, 950 cmÀ1; MS (m/z):
318 (M+). Anal. Calcd. for C21H34O: C, 79.19; H, 10.76. Found: C,
79.17; H, 10.75.
2.11. 3b-Acetoxy-17-oxa-5a-Androstan-16-one (8a)
Melting point (m.p.) 129–131 °C; 1H NMR (300 MHz, CDCl3): 0.9
(s, 3H); 1.1 (s, 3H); 0.9–1.9 (m, 20H, CH&CH2); 2.0 (s, 3H); 2.2 (m,
2H); 4.5 (m, 1H); 13C NMR (CDCl3): d = 34.2 (C-1); 28.2 (C-2); 62.9
(C-3); 33.1 (C-4); 40.9 (C-5); 27.2 (C-6); 31.7 (C-7); 37.1 (C-8);
56.9 (C-9); 36.5 (C-10); 19.8 (C-11); 38.2 (C-12); 74.3 (C-13); 53.5
(C-14); 35.9 (C-15); 43.1 (C-16); 178.2 (C-17); 173.3 (C–OCOCH3);
17.2 (C–CH3COO). IR (CHCl3): 1739, 1400, 1250, 950 cmÀ1; MS (m/
z): 348 (M+). Anal. Calcd. for C21H32O4: C, 72.38; H, 9.26. Found: C,
72.37; H, 9.23.
2.8. 17b-Acetoxy-3b-chloro-5a-Androstane (5a)
Melting point (m.p) 95–98 °C; IR (CHCl3): 1735, 1400, 1252,
950 cmÀ1; 1H NMR (300 MHz, CDCl3): 0.70 (s, 3H); 1.1 (s, 3H); 0.7–
2.0 (m, 22H, CH&CH2); 2.1 (s, 3H); 3.7 (m, 1H); 4.5 (m, 1H); 13C
NMR (CDCl3): d = 36.2 (C-1); 28.2 (C-2); 57.9 (C-3); 33.1 (C-4);
40.9 (C-4); 27.2 (C-6); 31.7 (C-7); 37.1 (C-8); 56.9 (C-9); 36.5 (C-
10); 19.8 (C-11); 38.2 (C-12); 41.3 (C-13); 53.5 (C-14); 20.9 (C-15);
31.1 (C-16); 84.2 (C-17); 171.3 (C–OCOCH3); 17.2 (C–CH3COO). IR
(CHCl3): 1732, 1400, 1250, 950; MS (m/z): 352 (M+); 354 (M++2).
Anal. Calcd. for C21H33ClO2: C, 71.46; H, 9.42. Found: C, 71.44; H,
9.39.
2.12. 3b-Chloro-17-oxa-5a-Androstan-16-one (9a)
Melting point (m.p.) 98–101 °C; 1H NMR (300 MHz, CDCl3): 0.9
(s, 3H); 1.1 (s, 3H); 0.9–2.1 (m, 20H, CH&CH2); 2.2 (m, 2H); 3.7 (m,
1H); 13C NMR (CDCl3): d = 36.2 (C-1); 28.2 (C-2); 57.9 (C-3); 33.1
(C-4); 40.9 (C-4); 27.2 (C-6); 31.7 (C-7); 37.1 (C-8); 56.9 (C-9);
36.5 (C-10); 19.8 (C-11); 38.2 (C-12); 75.1 (C-13); 53.5 (C-14);
35.9 (C-15); 43.1 (C-16); 178.1 (C-17). IR (CHCl3): 1739, 1400,
1250, 950 cmÀ1; MS (m/z): 324 (M+); 326 (M++2). Anal. Calcd. for
C19H29ClO2: C, 70.24; H, 9.00. Found: C, 70.21; H, 8.98.

J.M. Borah, P. Chowdhury / Steroids 76 (2011) 1341–1345
1345
2.13. 3b-Hydroxy-17-oxa-5a-Androstan-16-one (10a)
168.9. IR (CHCl3): 1766, 1250, 950 cmÀ1; MS (m/z): 136 (M+). Anal.
Calcd. for C8H8O2: C, 70.57; H, 5.92. Found: C, 70.54; H, 5.90.
Melting point (m.p.) 164–168 °C; 1H NMR (300 MHz, CDCl3): 0.9
(s, 3H); 1.1 (s, 3H); 0.9–2.1 (m, 21H, CH&CH2); 2.2 (m, 2H); 3.8 (m,
1H); 13C NMR (CDCl3): d = 36.2 (C-1); 28.2 (C-2): 72.9 (C-3); 33.1
(C-4); 40.9 (C-5); 27.2 (C-6); 31.7 (C-7); 37.1 (C-8); 56.9 (C-9);
36.5 (C-10); 19.8 (C-11); 38.2 (C-12); 74.9 (C-13); 53.5 (C-14);
35.9 (C-15); 43.1 (C-16); 178.2 (C-17). IR (CHCl3): 3200, 1739,
1400, 1250, 950 cmÀ1; MS (m/z): 306 (M+). Anal. Calcd. for
References
[1] Baeyer A, Villiger V. Chem Ber 1899;32:3625–33.
[2] Ten Brink GJ, Arends IWCE, Sheldon RA. Chem Rev 2004;104:4105–23.
[3] Harmata M, Rashatasakhon P. Tetrahedron Lett 2002;43:3641–4.
[4] Crudden C, Chen AC, Calhoun LA. Angew Chem Int Ed 2000;30:2851–5.
[5] Renz M, Meunier B. Eur J Org Chem 1999:737–50.
[6] Goodman R, Kishi Y. J Am Chem Soc 1998;120:9392–3.
[7] (a) Krow GR. Org React 1993;43:251–798;
C19H30O3: C, 74.47; H, 9.87. Found: C, 74.45; H, 9.84.
(b) Krow GR. Compr Org Synth 1991:671–88.
2.14. 3b,17b-Acetoxy-5 ,6 -epoxy-5 -Androstane (11a)
a
a
a
[8] Alvarez-Idaboy JR, Reyes L, Cruz J. Org Lett 2006;8:1763–5.
[9] Grein F, Chen AC, Edwards D, Crudden CM. J Org Chem 2006;71:861–72.
[10] Carlqvist P, Eklund R, Brink T. J Org Chem 2001;66:1193–9.
[11] Djerassi C. In: Steroid reactions: an outline for organic chemists. Holden-Day
Inc.: San Francisco; 1963. p. 457.
[12] Blickenstaff RT. In: Antitumor steroids. Academic Press: New York; 1992. p.
81–90.
[13] Seagaloff A, Meyers KD, Rongone E, Weethy JB, Cunningham M. Cancer
(Philadelphia) 1962;15:636–40.
[14] Petrow V, Padilla GM. Novel approaches to cancer chemotherapy. In: Sunkara
PS, editor. Academic Press: New York; 1984. p. 269–305.
[15] Zoppi S, Coconi M, Natali A, Constantine A, Seiro M, Martini L, et al. Clin
Endocrin Metab 1986;63:269–71.
[16] Cepa MMDS, Tavares de Silva EJ, Correia-da-Silva G, Roleira FMF, Teixeria NAA.
J Med Chem 2005;48:6379–85.
Melting point (m.p.) 150–154 °C; 1H NMR (300 MHz, CDCl3): 0.9
(s, 3H); 1.1 (s, 3H); 2.1 (bs, 6H); 0.8–2.09 (m, 19H, CH&CH2); 3.8
(m, 1H); 4.5 (m, 2H); 13C NMR (CDCl3): d = 34.2 (C-1); 28.2 (C-2);
62.9 (C-3); 33.1 (C-4); 71.2 (C-5); 57.8 (C-6); 31.7 (C-7); 37.1 (C-
8); 55.9 (C-9); 36.5 (C-10); 19.8 (C-11); 38.2 (C-12); 41.3 (C-13);
53.5 (C-14); 20.9 (C-15); 31.1 (C-16); 73.2 (C-17); 171.3 (C–
OCOCH3); 17.2 (C–CH3COO). IR (CHCl3): 1735, 1400, 1250,
950 cmÀ1; MS (m/z): 390 (M+). Anal. Calcd. for C23H34O5: C,
70.74; H, 8.78. Found: C, 70.73; H, 8.75.
2.15. 4-Nor-3-oxo-4-oxa-5a-Cholestane (12a)
[17] Djurendic EA, Sakac MN, Zavis MP, Gakovic AR, Canadi JJ, Andric SA, et al.
Steroids 2008;73:681–8.
[18] Chowdhury P, Borah JM, Goswami P, Das AM. Steroids 2011;76:497–501.
[19] Chowdhury P, Das AM, Goswami P. Steroids 2005;70:494–8.
[20] Borah P, Chowdhury PK. J Chem Res (S) 1996:502–3.
Melting point (m.p.) 113–116°; 1H NMR (300 MHz, CDCl3): 0.8 (s,
3H); 1.1 (s, 3H); 0.8–2.1 (m, 34H, CH&CH2); 2.2 (m, 2H); 4.1 (q,
J = 3.5 Hz, 1H); 13C NMR (CDCl3): d = 36.2 (C-1); 28.2 (C-2); 173.1
(C-3); 86.1 (C-5); 24.8 (C-6); 25.7 (C-7); 29.8 (C-8); 42.6 (C-9);
37.8 (C-10); 20.9 (C-11); 34.5 (C-12); 40.5 (C-13); 51.4 (C-14);
30.7 (C-15); 26.9 (C-16); 43.9 (C-17); 18.7 (C-18); 15.4 (C-19);
39.1 (C-20); 15.8 (C-21); 35.7 (C-22); 24.6 (C-23); 39.7 (C-24);
28.3 (C-25); 22.6 (C-26); 22.8 (C-27). IR (CHCl3): 1735, 1400, 1250,
950 cmÀ1; MS (m/z): 388 (M+). Anal. Calcd. for C26H44O2: C, 80.35;
H, 11.41. Found: C, 80.32; H, 11.39.
[21] (a) Borah P, Ahmed M, Chowdhury PK.
J Chem Res (M) 1998:1173–8;
(b) Borah P, Ahmed M, Chowdhury PK. J Chem Res (S) 1998:236–8; (c)
Goswami P, Hazarika S, Borah P, Chowdhury PK. Ind
2003;42B:678–82.
J
Chem
[22] Hazarika S, Goswmi P, Chowdhury PK. Ind J Chem 2003;42B:1706–10.
[23] Chowdhury PK, Bordoloi MJ, Barua NC, Goswami PK, Sarmah HP, Sharma RP,
et al. US Pat. No: 5808,117.
[24] (a) Boyce R, Li G, Nestler HP, Suenaga T, Still WC.
1994;116:7955–6; (b) Cheng Y, Suenaga T, Still WC.
1996;118:1813–4.
J
J
Am Chem Soc
Am Chem Soc
[25] Madder A, Li L, De Muyunck H, Farcy N, Van Haver D, Fant F, et al. J Comb Chem
2002;4:552–62 [and references cited therein].
2.16. Phenyl benzoate (13a)
[26] Ding B, Taotofa U, Orsak T, Chadwell M, Savage PB. Org Lett 2004;6:3433–6.
[27] Goswami P, Hazarika S, Das AM, Chowdhury PK. Ind
2004;43B:1275–81.
J
Chem
Melting point (m.p.) 67–70 °C; 1H NMR (300 MHz, CDCl3):
6.8–7.2 (m, 5H), 7.6–8.2 (m, 5H); 13C NMR (CDCl3): d = 122.1;
126.4; 129.3; 130.9; 151.2; 173.1. IR (CHCl3): 1735, 1400, 1250,
950 cmÀ1; MS (m/z): 198 (M+). Anal. Calcd. for C13H10O2: C, 78.77;
H, 5.09. Found: C, 78.75; H, 5.06.
[28] Rothman ES, Wall MS, Eddy CR. J Am Chem Soc 1954;76:527–32.
[29] Koch SSC, Chamberlin AR. Syn Comm 1989;19:829–33.
[30] (a) Hamelin J, Bazureau J-P, Boullet FT. In: Loupy A, editor. Microwaves in
organic chemisry, 2nd ed. Wiley-VCH: Weinheim, Germany, 2003. p. 253
[chapter 8]; (b) de la Hoz A, Diaz-Ortiz A, Moreno A. Chem Soc Rev
2005;34:164; (c) Kappe CO, Chem Soc Rev 2008;37:1127.
[31] Bezdushna E, Ritter H. Macromol Rapid Commun 2007;28:443–8.
[32] Loupy A, Perreux L, Liagre M, Burle K, Moneuse M. Pure Appl Chem
2001;73:161–4.
2.17. Phenyl acetate (14a)
[33] Carsten K, Iannelli M, Kerep P, Klink M, Schmitz S, Sinnwell S, et al.
Tetrahedron 2006;62:4709–14.
[34] Riveria DG, Pando O, Suardiaz R, Coll F. Steroids 2007;72:466–73.
Melting point (m.p.) 195 °C; 1H NMR (300 MHz, CDCl3): 6.2–7.3
(m, 5H), 2.1 (s, 3H); 13C NMR (CDCl3): d = 20.3; 121.4; 126.2; 129.2;