PhI=Nses mediated aziridination of 11-pregnane derivatives: synthesis of an 11,12-aziridino analogue of neuroactive steroids

DI CHENNA PABLO H.; DAUBAN, P.; GHINI, ALBERTO A.; BAGGIO, RICARDO; GARLAND, M. TERESA; BURTON, GERARDO; DODD, R. H.

TETRAHEDRON

Elsevier

Año: 2003 vol. 59 p. 1009 - 1014

0040-4020

Abstract—Reaction of 11-pregnene-3,20-dione (6) or 3-a-acetoxy-11-pregnen-20-one (12) with trimethylsilylethanesulfonyl (‘Ses’) iminoiodinane 5 in the presence of copper (I) triflate gave the corresponding a,a-11,12-aziridino steroids 7 and 13 in 53 and 45% yields, respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). iminoiodinane 5 in the presence of copper (I) triflate gave the corresponding a,a-11,12-aziridino steroids 7 and 13 in 53 and 45% yields, respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). iminoiodinane 5 in the presence of copper (I) triflate gave the corresponding a,a-11,12-aziridino steroids 7 and 13 in 53 and 45% yields, respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). iminoiodinane 5 in the presence of copper (I) triflate gave the corresponding a,a-11,12-aziridino steroids 7 and 13 in 53 and 45% yields, respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). iminoiodinane 5 in the presence of copper (I) triflate gave the corresponding a,a-11,12-aziridino steroids 7 and 13 in 53 and 45% yields, respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). —Reaction of 11-pregnene-3,20-dione (6) or 3-a-acetoxy-11-pregnen-20-one (12) with trimethylsilylethanesulfonyl (‘Ses’) iminoiodinane 5 in the presence of copper (I) triflate gave the corresponding a,a-11,12-aziridino steroids 7 and 13 in 53 and 45% yields, respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-N-methyl aziridinosteroids 9 and 15, respectively. The latter is a conformationally constrained analogue of the endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). endogenous neurosteroid pregnanolone (1). respectively. The Ses group of each compound was removed using the TASF reagent and the resulting free aziridine NH was methylated to afford the 11a,12a-