186887-38-7Relevant academic research and scientific papers
Asymmetric Total Synthesis of (+)-Apovincamine and a Formal Synthesis of (+)-Vincamine. Demonstration of a Practical "Asymmetric Linkage" between Aromatic Carboxylic Acids and Chiral Acyclic Substrates
Schultz, Arthur G.,Malachowski, William P.,Pan, You
, p. 1223 - 1229 (2007/10/03)
Asymmetric syntheses of (+)-apovincamine (la) and (+)-vincamine (2) are described. Construction of the pentacyclic diene lactam 14, a pivotal intermediate for synthesis of the cis-fused vincane-type alkaloids, began by Birch reduction - alkylation of the chiral benzamide 3 to give the 6-ethyl-l-methoxy-4-methyl-l,4-cyclohexadiene 4. Conversion of 4 to 2,5-cyclohexadienone 5 (92percent overall yield from 3) and HPLC analysis of 5 demonstrated the diastereomeric purity resulting from the Birch reduction - alkylation to be > 100:1. Dienone 5 was converted to butyrolactone 9 (47percent overall yield from 3), and 9 was coupled with tryptamine (10) to give the amide lia. Amido keto aldehyde 13 was obtained from 11a, and acid-catalyzed tricyclization and subsequent base-induced elimination of MeOH provided the desired cis-fused pentacyclic diene lactam 14. Examination of the two-step process 13 -14 revealed a novel base-induced epimerization at C(21) which served to interconvert 14 and 17, possibly by the involvement of a homoenolate. Diene lactam 14 was converted to (+)-apovincaminal 20a, an intermediate in the synthesis of (+)-apovincamine (la) reported by Winterfeldt and co-workers. A new procedure for conversion of 20a to la involves conversion of 20a to the acetal 20b and treatment of 20b with NBS/AIBN in CCl4. The conversion of la to vincamine (2) has been reported by Oppolzer and co-workers.
