Enantioselective Synthesis of 1S,3S,5S- and 1R,3S,5R-2-Azabicyclo[3.3.0]octane-3-carvoxylic Acid Starting from L-Serine

Abstract

15,35,5S)-and (1R,3S,5R)-2-Azabicyclo[3.3.0loctane-3-carboxylicacid have been synthesized by intramolecular r a d i c a l c y c l ~s a t i o n of methyl 2-(5)-IN-benzyloxycar bonyl-N-(Z-cyclopenten-l-yl)amino]-3-iodopropionate and subsequent reactions.(1S,3S,55)-2-Azabicyclo[3.3.0loctane-3-carboxylicacid 1 and (lR,3S,5R)-2-azabicyclo[3.3.01octane-3-carboxylicacid 2 are precursors o f the h i g h l y potent angiotensin converting enzyme 2 i n h i b ~t o r s 3'''( r a m i p n l a t ) and 4 .i n order t o prepare these i n h i b i t o r s f o r i n v e s t i g a t i n g the s t r u c t u r e a c t i v l t y r e l a t i o n s h i p i n v i t r o Z a we had t o synthesize 1 and 2 as intermediates.2 Recently, we reported the synthesis o f racemic 12,3 and .To avoid the r e s o l u t i o n of the racemic benzyl e s t e r of 1 or 2 i n preparing 1 and $'3 we looked f o r an enantioselective synthesis.I t was