This paper describes our efforts towards the asymmetric total synthesis of (+)-actinophyllic acid. Starting from the chiral oxazolidinone 9, an azocino [4,3-b]indolyl intermediate (5) possessing the A/B/C ring system and the C16 quaternary stereogenic center of actinophyllic acid has been synthesized. Key steps include a LHMDS-promoted condensation to establish the critical C2–C16 bond and a successive four-step transformation to assemble the eight-membered C-ring of the target molecule.Download high-res image (163KB)Download full-size image

A practical asymmetric synthesis of the trans-fused 2-methyl-5-hydroxyldecahydroquinolines 8a and 8b is reported. Double Michael addition of enone 4 with (S)-phenylethylamine generated separable C2-methylated decahydroquinolinones 5a and 5b, which were converted to 8a and 8b via several functional group transformations.

Multisubstituted chiral butyrolactonimidates have been synthesized via a one-pot, three-step cascade reaction in which (R)-N-tert-butanesulfinyl imidates and α,β-unsaturated diesters undergo highly stereoselective Michael addition, anion-oxidative hydroxylation, and cyclization. The synthesized butyrolactonimidates are versatile intermediates for preparation of substituted butyrolactones and furans. The usefulness of this cascade reaction is demonstrated through the concise total synthesis of natural product (−)-nephrosteranic acid.

A new series of physostigmine analogues 3a—3j with modifications at the C3a and C5 positions was designed and synthesized. Bioassay of the synthetic analogues 3a—3j, along with the previous synthesized C3a-ethyl-C5-triazole physostigmine analogues 1a—1g and 2a—2j was performed, which indicates that the replacement of the carbamoyl moiety of C3a-ethyl-C5-triazole analogues 1 and 2 with a triazole moiety decreased acetylcholinesterase(AchE) inhibitory activity, whereas the introduction of heterocycles into the triazole ring increased both AChE and butyrylcholinesterase(BchE) inhibitory activities. Structure-activity relationship(SAR) studies of C3a-methyl-C5-triazole analogues 3 reveal the C3a-methyl substituent is important for AChE and BChE inhibition and the introduction of a second ionizable N center improved the binding of the synthetic analogues to both AChE and BChE.