Runanine

Memory of Chirality in Bromoalkyne Carbocyclization: Applications in Asymmetric Total Synthesis of Hasubanan Alkaloids.[Pubmed:30548073]

Org Lett. 2019 Jan 4;21(1):292-295.

A transition-metal-free 5- exo- dig asymmetric cyclization of alpha-amino ester enolates onto bromoalkynes provided a product with excellent enantioselectivity via the memory of chirality concept. This strategy was applied to a concise total synthesis of (-)-Runanine and a formal synthesis of (-)-8-demethoxyRunanine and (-)-cepharatine D.

The Hasubanan and Acutumine Alkaloids.[Pubmed:26521650]

Alkaloids Chem Biol. 2014;73:161-222.

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.

Synthesis of isohasubanan alkaloids via enantioselective ketone allylation and discovery of an unexpected rearrangement.[Pubmed:19072324]

J Org Chem. 2009 Feb 6;74(3):1187-99.

A synthesis of the hasubanan alkaloids hasubanonine, Runanine, and aknadinine via a unified route was attempted. Construction of key phenanthrene intermediates by a Suzuki coupling-Wittig olefination-ring-closing metathesis sequence allowed a convergent and flexible approach. Conversion of the phenanthrenes into the target structures was projected to involve six steps including phenolic oxidation, ketone allylation, anionic oxy-Cope rearrangement, and acid-promoted cyclization. The final step was thwarted by a pinacol-like rearrangement that delivered the unnatural isohasubanan alkaloid skeleton. The structures of the products were established by exhaustive NMR experiments and confirmed by GIAO (13)C NMR calculations of Runanine, isoRunanine, and three other isomers. These computations revealed some inconsistencies with the benzene solvent correction which suggest that caution should be used in employing this algorithm. The racemic synthesis of isohasubanonine was transformed into an enantioselective synthesis by the discovery that Nakamura's chiral bisoxazoline-ligated allylzinc reagent mediates the enantioselective allylation of ketone 19 in 93% ee. This method could be extended to three other structurally related ketones (92-96% ee), and the enantioselective syntheses of two other isohasubanan alkaloids, isoRunanine and isoaknadinine, were accomplished. Racemic isohasubanonine was found to be an ineffective analgesic agent.