Lactams hydroxy, from imides

A series of N-substituted narceine amides (Section III,D,1) was prepared from 101 under the action of primary amines (100). Acid-catalyzed dehydration transformed these amides to corresponding imides (ene lactams) of the ( )-narceine imide (117) type (100). Similar transformations were performed in the hydrastine series (101). JV-Methylhydrastine (98) when treated with dilute ammonium hydroxide gave hydroxy lactam 127, which was dehydrated to (Z)-fumaridine (113) (5). Sodium borohydride was able to reduce the stilbene double bond in 98 to produce saturated lactone 132 (5). 

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

A different approach to enantiotopic group differentiation in bicyclic anhydrides consists of their two-step conversion, first with (/ )-2-amino-2-phcnylethanol to chiral imides 3, then by diastereoselective reduction with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) to the corresponding chiral hydroxy lactames 4, which may be converted to the corresponding lactones 5 via reduction with sodium borohydride and cyclization of the hydroxyalkyl amides 101 The overall yield is good and the enantioselectivity ranges from moderate to good. Absolute configurations of the lactones are based on chemical correlation. 

Cyclic imide reduction. The reagent reduces imides to give hydroxy lactams in a regioselective manner, which is different from LiBHEtj. The complementary is very useful in synthesis. 

To complete the total S3mthesis of ent-staurosporine (2), a two-step deprotection strategy (hydrogenation followed by aminal hydrolysis) delivered 64 from 63 in high yield (Scheme 8). Danishefsky et al. preferred to clarify the monosaccharide domain prior to reducing the maleimide function [45], The most efficient method involved reduction of the imide group with sodium borohydride to provide a mixture of hydroxy lactams. Further reduction... 

---