Synthesis of novel 16-spiro steroids: 7-(Aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazolo estrone hybrid heterocycles

• 1,3-Dipolar cycloaddition of azomethine ylides to C-16 exocyclic steroidal dipolarophiles.
• Generation of a library 40 novel C-16 spiro estrones hybrid heterocycles.
• The azomethine ylide cycloaddition proceeds stereo-specifically.
• Regio- and facial-selectivity were observed in the cycloaddition.
• Structure of all the C-16 spiro estrones elucidated with 1 and 2D NMR spectroscopy.

The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of isatins or acenaphthylene-1,2-dione and 1,3-thiazolane-4-carboxylic acid to various exocyclic dipolarophiles synthesized from estrone afforded a library of novel C-16 spiro oxindole or acenaphthylene-1-one – 7-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole – estrone hybrid heterocycles. These reactions occur regio- and stereo-selectively affording a single isomer of the spiro estrones in excellent yields with the formation of two C–C and one C–N bonds along with the generation of four new contiguous stereo-centers in a single step.

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