The first active aza analogue of narciclasine was synthesized from a pentasubstituted derivative of nicotinic acid. The key features of the synthesis include a halogen dance of bromopyridine and an intramolecular Heck reaction with a conduramine derived chemoenzymatically from bromobenzene. 10-Aza-narciclasine was found to have reasonable activity against several cancer cell lines.

The requirement of aryl ring activation by strong-electron withdrawing substituents in substrates for the intramolecular nucleophilic aromatic substitution reaction known as the Truce-Smiles rearrangement was examined. Preliminary mechanistic experiments support the SNAr mechanism, including (1)H and (13)C NMR spectra of a Meisenheimer intermediate formed in situ. The rearrangement was generally observed to be successful for substrates with strong electron withdrawing substituents, such as nitro-, cyano-, and benzoyl- functional groups, but also for those with multiple, weakly electron withdrawing substituents, such as chloro- and bromo-functional groups. These results lend further clarification to the effect of aryl substituents in this type of SNAr reaction. Additionally, the survey revealed several tandem cyclization and/or elimination reactions accessed by certain substrates.

Synthesis and Biological Activity of 10-Aza-narciclasine. -Title compound (VI) is synthesized starting from pyridine derivative (I) over 12 steps in an overall yield of 2.05%. The key steps are the halogen dance reaction of (II) and the intramolecular Heck reaction of imide (IV). Compound (VI) is found to have reasonable activity against several cancer cell lines. -(VSHYVENKO, S.; W'GIORGIS, Z.; WEBER, A.; NEVEROVA, N.; HEDBERG, B.; HUDLICKY*, T.; Adv. Synth. Catal. 357 (2015) 1, 83-87, http://dx.doi.org/10.1002/adsc.201400993 ; Dep. Chem., Brock Univ., St. Catharines, Ont. L2S 3A1, Can.; Eng.) -R. Langenstrassen 22-246

Truce-Smiles Rearrangement of Substituted Phenyl Ethers. -The substrate scope of the title reaction with regard to the electronic and steric properties of the aryl substitution pattern is thoroughly evaluated. Thus, the reaction tolerates strongly electron-withdrawing substituents such as nitro-, cyano-and phenylcarbonyl groups as well as di-and trisubstituted chloro-and bromo-substitution patterns, but no fluoroor iodine-substituents. Depending on the substituents' position on the aryl ring yields range from low to excellent, and further tandem cyclization and/or elimination processes may inevitably take place. -(KOSOWAN, J. R.; W'GIORGIS, Z.; GREWAL, R.; WOOD*, T. E.; Org. Biomol. Chem. 13 (2015) 24, 6754-6765, http://dx.doi.org/10.1039/C5OB00812C ; Dep. Chem., Univ. Winnipeg, Winnipeg, Manitoba R3B 2E9, Can.; Eng.) -F. Schill 42-053