NEW METHOD OF PREPARATION OF BRASSINOSTEROIDS

Article abstract of DOI:10.1135/cccc19940457

Brassinosteroids with lactone B-ring (II and IV) were prepared by oxidation of the corresponding 6-keto derivatives I and III without protection of the hydroxyl groups against the action of the oxidation reagent.

Full text of DOI:10.1135/cccc19940457

Short Communication
457
NEW METHOD OF PREPARATION OF BRASSINOSTEROIDS*
Ladislav KOHOUT
Institute of Organic Chemistry and Biochemistry,
Academy of Sciences of the Czech Republic, 166 10 Prague 6, The Czech Republic
Received February 4, 1993
Accepted March 22, 1993
Brassinosteroids with lactone B-ring (II and IV) were prepared by oxidation of the corresponding
6
-keto derivatives I and III without protection of the hydroxyl groups against the action of the oxida-
tion reagent.
In the synthesis of brassinolide, 24-epibrassinolide (24R-brassinolide), homobrassi-
nolide, and other brassinolides with B-lactone ring, the last steps consist in the prepara-
tion of the lactone from the corresponding 6-keto derivative. According to the hitherto
1
– 5
used reaction sequence
, the vicinal diol grouping in the corresponding 6-keto deri-
vative (in the A-ring, as e.g. in Ia, but also in the side-chain, as e.g. in III) is protected,
usually as diacetate which is then subjected to Baeyer–Villiger oxidation to give the
B-homo-lactone (e.g. IIa) with protected diol grouping(s). The deprotection is usually
realized by alkaline hydrolysis whereupon the lactone ring has to be closed again in an
acid medium.
In the course of our investigations on brassinosteroids we have found that no protec-
tion of the diol grouping is necessary and that the Baeyer–Villiger oxidation can be
performed directly with the dihydroxy (Ia – If) or tetrahydroxy (III) 6-ketone, making
thus the synthesis of brassinosteroids shorter. This method of preparation was already
6
used by us in one of our previous studies . In this paper we show that this reaction can
be applied also to other 6-ketones (Scheme 1). We converted the corresponding
6
2
-ketones I and III into lactone II and 24-epibrassinolide IV [(22R,23R,24R)-
α,3α,22,23-tetrahydroxy-24-methyl-B-homo-7-oxa-5α-cholestan-6-one]. As seen from
Table I, this procedure not only shortens the synthetic pathway but also gives higher
yields.
*
Part CCCLXXIII in the series On Steroids; Part CCCLXXII: Collect. Czech. Chem. Commun. 59, 435
1994).
(
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58
Kohout:
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Short Communication
459
EXPERIMENTAL
Melting points were determined on a Kofler block and are uncorrected. Infrared spectra were re-
corded on a Zeiss UR 20 spectrometer in tetrachloromethane solution (unless stated otherwise),
−1
wavenumbers are given in cm . Proton NMR spectra were taken in deuteriochloroform on a Varian
XL-200 instrument (FT mode, 200 MHz) with tetramethylsilane as internal standard and the data
1
were interpreted as the first-order spectra. H NMR spectra and IR spectra of the prepared samples
1
,7,10
were identical with those given in the literature
. Preparative TLC was carried out on 200 × 200 mm
plates coated with 0.7 mm thick layer of silica gel Woelm DC. The light petroleum was a fraction
boiling at 40 – 62 °C.
Oxidation of 6-Ketones with Trifluoroperoxyacetic Acid
A solution of trifluoroperoxyacetic acid (prepared from trifluoroacetic anhydride (0.63 g, 3.0 mmol)
and 50% hydrogen peroxide (0.10 g, 1.5 mmol) in dichloromethane (1.5 mm) immediately before
use) was added to a solution of the 6-keto derivative (0.2 mmol) in dichloromethane (8 ml). The
mixture was allowed to stand at room temperature for 24 h, the reaction course being monitored by
TLC. The mixture was poured into water and the product was taken up in chloroform. The chloro-
form extract was washed with water, 5% aqueous solution of potassium hydrogen carbonate and
water, dried and the solvent was evaporated in vacuo. The residue was purified by preparative thin-
layer chromatography on silica gel in chloroform–isopropanol (9 : 1). Work-up of the appropriate
fractions gave the desired lactone. For physical properties of the obtained lactones see Table I.
Oxidation of 6-Ketones with 3-Chloroperoxybenzoic Acid
A solution of the 6-keto derivative (0.2 mmol) in dichloromethane (10 ml) was mixed with solid 70%
3
5
-chloroperoxybenzoic acid (0.74 g, 3 mmol) and the mixture was set aside at room temperature for
– 21 days, the reaction course being monitored by TLC. After the reaction had ended, the mixture
was poured in water and worked up in the same manner as described in the preceding experiment.
TABLE I
Melting points and yields of the synthesized lactones (yields given for oxidation with trifluoro-
peroxyacetic acid; yields of oxidation with 3-chloroperoxybenzoic acid were about 10 – 15 % lower)
Reported
Ketone
Lactone
M.p., °C
Yield, %
M.p., °C
Yield, %
Ref.
Ia
Ib
Ic
Id
Ie
If
IIa
IIb
IIc
IId
IIe
IIf
185 – 188
136 – 138
212 – 215
242 – 245
195 – 197
oil
85
67
69
88
72
78
53
186 – 188
oil
15
10
7
8
212 – 215
244 – 247
195 – 197
oil
62
9
55
9
46
10
10
1
27
III
IV
255 – 257
256 – 258
<40
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

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Kohout:
The residue, obtained after evaporation of chloroform, was purified by chromatography on thin layers
of silica gel (elution with chloroform–isopropyl alcohol 9 : 1) or on a small column of silica gel
(
elution with chloroform–ether 1 : 1). Properties of the thus-obtained lactones agreed with those of
lactones prepared according to the preceding procedure (oxidation with trifluoroperoxyacetic acid).
The author is indebted to Dr J. Smolikova for interpretation of IR spectra measured by Mrs
K. Matouskova. Proton NMR spectra were recorded by Mrs J. Jelinkova and Mrs M. Snopkova. The
technical assistance of Mrs J. Neumannova is gratefully acknowledged.
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Translated by M. Tichy.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)