Synthesis of aziridinosteroids

Article abstract of DOI:10.3390/50300443

11α,12α-aziridinosteroids (2a, b, c) were prepared from 5β-H-11-pregnene-3, 20-dione (1) using different iminophenyliodinanes and cloramine aziridination reagents.

Full text of DOI:10.3390/50300443

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Synthesis of Aziridinosteroids
1
2
1
1
2
P. Di Chenna , P. Dauban , A. A. Ghini , G. Burton and R. H. Dodd
1
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Bue-
nos Aires, Pabellón II, Ciudad Universitaria, 1428 Buenos Aires. Argentina
2
Institut de Chimie des Substances Naturelles. CNRS. Gif-sur-Yvette. (91198). Francia
E-mail: Robert.Dodd@icsn.cnrs-gif.fr
Abstract: 11α,12α-aziridinosteroids (2a, b, c) were prepared from 5β-H-11-pregnene-3,
2
0-dione (1) using different iminophenyliodinanes and cloramine aziridination reagents.
Introduction
The presence of an heteroatom, either replacing a methylene group of the steroid nucleus or as a
substituent gives rise to major changes in the biological activity of steroid derivatives [1]. Thus, many
steroidal nitrogen derivatives are pharmacologically important. Furthermore, 12α-amino steroids have
recently found application as chiral templates for combinatorial synthesis [2]. As an alternative way to
introduce nitrogen functionalities into the steroid nucleus, we have explored the aziridination of steroi-
dal double bonds. Aziridine ring opening with a nucleophile would yield aminosteroids with defined
stereochemistry [3,4]. We describe the synthesis of 11α,12α-aziridinosteroids (2a, b, c) by reaction of
11-pregnen-3,20-dione (1) with different aziridination reagents.
O
O
RN
RSO N=IPh
2
acetonitrile
O
O
or
H
H
acetonitrile/DCM
1
2a R = Ts
2b R = Ns
2c R = SES
Experimental
Typical aziridination procedure: Copper (I) triflate (0.065 mmol) and 11-pregnen-3,20-dione (1,
0.65 mmol) were added under argon to a suspension of molecular sieves 4 Å (185 mg) in dry acetoni-
trile (1.65 ml). SES-iminophenyliodinane (1.7 eq) was then added in 15 portions every 30 min with

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vigorous stirring and stirring continued for 24 h at 25°C. The reaction mixture was filtered, evaporated
to dryness and purified by column chromatography to yield 2c (53% yield).
Results and Discussion
The aziridination reaction was carried out on several olefins (ciclohexene, styrene, norbornene,
methyl acrylate, etc.) with a series of N-sulfonyl iminophenyliodinanes and N-SES chloramine sodium
salt and different catalysts (Cu (I) and Cu (II) triflate, PTAB, Py.HBr ). With ciclohexene and (p-
3
chlorobenzenesulfonyl)-iminophenyl iodinane the aziridine was obtained in 52% yield; cleavage with
thiophenol followed by removal of the PhS group gave cycloheylamine in 95% yield.
Steroid 1 was treated with (tosylsulfonyl) and (nosylsulfonyl)-iminophenyliodinane in acetonitrile-
dichloromethane 1:1, rendering stereospecifically the 11α,12α-aziridinosteroid (2a, b) with moderate
yields (25-30%). Stereochemistry was established from the NOESY spectra (correlations H-19/H-11β
and H-18/H-12β).
Attempts to aziridinate the 5,6 double bond in pregnenolone and pregnenolone acetate gave com-
plex mixtures. On the other hand, the 4,5 conjugated double bond in progesterone was inert under the
reaction conditions used.
To facilitate the deprotection step to give the free aziridine, (N-(2-trimethylsilyl)-ethanesulfonyl)-
iminophenyliodinane (PhI=NSES) was used as aziridination reagent. In this case, using acetonitrile as
solvent, 1 rendered derivative 2c in 53% yield. Aziridination of 1 with the sodium salt of (N-(2-
trimethylsilyl)-ethanesulfonyl)-chloramine in acetonitrile gave 2c in only 27% yield.
Acknowledgements: We thank Universidad de Buenos Aires, ANPCYT (Argentina) and ECOS
(
France) for financial support.
References and Notes
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2.
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4.
Suginome, H.; Yamada, S.; Wang, J.B. J. Org. Chem. 1990, 55, 2170.
Pavis, A.P.; Lawless, L.J. J. C. S. Chem. Comm. 1999, 9.
Dauban, P.; Chieroni, A.; Riche, C.; Dodd, R.H. J.Org. Chem. 1996, 61, 2488.
Fioravanti, S.; Pellacani, L.; Tabanella, S.; Tardella, P. A. Tetrahedron 1998, 54, 14105.