The synthesis of steroidal 16α,17α‐fused isoxazolines and isoxazolidines

Abstract

The reaction of nitrile oxides with Ai6-steroids substituted at C-17 by COCH3, OCOCH,, CN, NHCOCH3 and H afforded 1601, 17~-[3,1-(2-isoxazolino)]-steroids. From the reaction of C ,N-diphenylnitrone with pregna-5,16-diene-3p-ol-2O-one acetate two isomeric products were isolated, 1601, 1701 -(2,3-diphenyl-3 ,l-isoxazolidino)-pregn-5-en-3p-ol-20one acetate and 1601,17a -(2,3 -diphenyl -1 , 3isoxazolidino)-pregn-5-en-3p-01 -20 -one acetate.Certain steroids containing a heterocyclic ring fused at positions C -1 6 and C-17, such a s the 1601,17adioxolane derivatives of 901 -fluoro-l601hydroxyprednisolone (1) and of 1601,17a -dihydroxyprogesterone (2) have been reported by other investigators. The present investigation was undertaken in order to prepare steroids having other heterocyclic ring systems fused at these positions.The cycloaddition of 1 , 3 -dipolar reagents to unsaturated compounds, which has been reviewed by Huisgen (3), affords a simple method for the synthesis of five-membered nitrogen-containing heterocycles. The 1,3-cycloaddition of nitrile oxides to olefins affords A'-isoxazolines (4), and i t was of interest to use this reaction a s a direct method for synthesizing isoxazolino-steroids. While this paper was being written Fritsch, Seidl and Ruschig (5) reported that benzonitrile oxide and acetonitrile oxide added to 30acetoxypregna-5,16-dien-2O-one (Ia) to give isoxazolines with structure VIa (Ri =

Isoxazolidine: A Privileged Scaffold for Organic and Medicinal Chemistry

“…Steroids are a valuable class of polycyclic natural products that exhibit an interesting potential for a wide range of pathologies such as prostatic diseases or cancers. , The first isoxazolidinyl steroid described was the 16α,17α-fused isoxazolidine 372 , reported in 1964 by Culbertson et al . (Figure ).…”

“…307 Steroids are a valuable class of polycyclic natural products that exhibit an interesting potential for a wide range of pathologies such as prostatic diseases 308 or cancers. 309,310 The first isoxazolidinyl steroid described was the 16α,17α-fused isoxazolidine 372, reported in 1964 by Culbertson et al 311 (Figure 26). Using the 1,3-DC methodology (see section 3.1), a complex mixture of isomers was obtained from which only two of them were isolated in 6% and 15−28% yields.…”

Intramolecular approach to some new D-ring-fused steroidal isoxazolidines by 1,3-dipolar cycloaddition: synthesis, theoretical and in vitro pharmacological studies

“…However, D-ring-fused isoxazolidines have received less attention from both synthetic and pharmacological aspects. 22 Since isoxazolidines 9 and 12b-e were formed within a project aimed at the synthesis of novel fivemembered N,N-and N,O-heterocyclic frameworks from 2 by 1,3-dipolar cycloaddition, in vitro pharmacological studies of all the products seemed obvious. Investigation of the inhibitory effects of arylpyrazolines (4a-h, Fig.…”