Convergent Synthesis of Naphthylisoquinoline Alkaloids: Total Synthesis of (+)-O-Methylancistrocline.
A highly convergent synthesis of the methyl ether derivative 2a of the naphthylisoquinoline alkaloid ancistrocline (2) is described. The key step involves a stereoselective biaryl coupling between the chiral oxazoline 3 and the Grignard reagent 4 derived from the optically active tetrahydroisoquinoline 8. The atropisomeric mixture was then converted to the separable acetamides 11 and 12, which were obtained in a ratio of 16:84 and an overall yield of 32% for the three steps. The major atropisomer 12 was then converted into O-methylancistrocline (2a), which was identical to a semisynthetic sample derived from the related alkaloid ancistrocladinine (14).
Chau
Phung
P
Institut für Organische Chemie der Universität, Am Hubland, D-97074 Würzburg, Federal Republic of Germany.
Czuba
Ivona R.
IR
Rizzacasa
Mark A.
MA
Bringmann
Gerhard
G
Gulden
Klaus-Peter
KP
Schäffer
Manuela
M