The Hasubanan and Acutumine Alkaloids.

Research in the hasubanan and acutumine alkaloid fields up to 1970 was discussed under "morphine alkaloids" in Volume 13 of this chapter. Advances in the field of hasubanan alkaloids from 1971 to 1975 were reviewed in Volume 16 and from 1976 to 1986 in Volume 33. This chapter extends the information in the three preceding reviews to hasubanan alkaloid literature published from 1987 to June 2013. This chapter covers acutumine alkaloid literature since (-)-acutumine (3) was isolated in 1929. This chapter includes occurrence and physical constants, new alkaloids, synthesis, biosynthesis, and pharmacology. Section 1 introduces the foremost alkaloids, (-)-hasubanonine (1) and (-)-acutumine (3), and the numbering systems of the hasubanan (2) and acutumine (4) skeletons. Section 2 details the occurrence and physical constants of 29 new hasubanan and 15 acutumine alkaloids. The isolation and structural determination of these new alkaloids are described in Section 3. Section 4 summarizes total syntheses and synthetic studies toward hasubanan and acutumine alkaloids. Completed syntheses of the hasubanan alkaloids (+)-cepharamine (ent-71), (-)-hasubanonine (1), (-)-runanine (8), (-)-delavayine (6), (+)-periglaucine B (19), and (-)-8-demethoxyrunanine (12) are reviewed. Completed syntheses of (-)-acutumine (3) and (-)-dechloroacutumine (52) are also described. Section 5 details biosyntheses of (-)-acutumine (3) advanced by Barton, Wipf, and Sugimoto. Section 6 summarizes pharmacological studies of hasubanan and acutumine alkaloids. Opioid receptor affinity, anti-HBV activity, and antimicrobial activity of hasubanan alkaloids are reported. Antiamnesic properties, cytotoxicity, and anti-HBV activity of acutumine alkaloids are described.