From Berbines to Protopines: Regiocontrolled Hofmann Elimination/Hydroboration/Oxidation of N‐Substituted Berbinium Salts

Abstract

An improved synthetic approach to protopines based on the sequential Hofmann elimination, hydroboration and oxidation of N‐(arylmethyl)berbinium salts has been designed. By using berberine chloride as the starting material, this sequence of reactions has provided two new nonnatural protopines, N‐benzyl‐N‐nordihydroallocriptopine and N‐(p‐methoxybenzyl)‐N‐nordihydroallocriptopine and the natural allocriptopine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Total Synthesis of New 8‐(Arylmethyl)berbines

“…[18] Thus, treatment of berbine 7 with p-(trityloxy)benzyl bromide and K 2 CO 3 in dichloromethane, resulted in the formation of a cis/trans mixture of diastereoisomers 8 in a 1.5:1 ratio, which was separated by column chromatography (Scheme 3).…”

Diastereoselective Synthesis of 1,2‐Disubstituted 2,3,4,5‐Tetrahydro‐1H‐3‐benzazepines by Means of the Stevens Rearrangement

“…We employed the Bischler-Napieralski cyclization of the corresponding amide followed by Nmethylation and reduction to afford the isoquinoline intermediate 4. The standard N-alkylation of this compound [14] yielded the cis/trans mixture of diastereoisomers 5a in a 5:95 ratio. The trans diastereoisomer was isolated from this mixture by fractional precipitation.…”

Dihydroallocryptopine

“…For the biological activity of allocryptopine derivatives, see: Morteza et al (2003); Yan et al (2009); Capasso et al (1997); Jeong et al (2009); Zhao et al (2008). For a related structure, see: Valpuesta et al (2006).…”