Kingianin A: A New Natural Pentacyclic Compound from Endiandra kingiana

Abstract

A new natural pentacyclic compound, named kingianin A, was isolated as a racemic mixture from the barks of Endiandra kingiana (Lauraceae). Its structure was elucidated by comprehensive analysis of NMR spectroscopic data, X-ray crystallography, and ECD calculations. The pentacyclic skeleton may be formed by a Diels-Alder reaction between two monomers having a bicyclo[4.2.0]octadiene backbone formed by a stereospecific electrocyclization of a linear compound of polyketide origin.

Total Synthesis of Kingianins A, D, and F

“…The synthesis of (AE)-kingianins A (1) and D (14) was eventually optimized to a sequence involving oxidation of alcohol 11 using the tetrapropylammonium perruthenate/ N-methylmorpholine-N-oxide (TPAP/NMO) conditions of Stark et al, [34] with the product directly subjected to radical cation Diels-Alder dimerization using the Ledwith-Weitz salt (13; 5 mol %). [1] This radical cation Diels-Alder dimerization is a remarkably selective reaction, with only three of the potential thirty-two isomeric products isolated. Column chromatography afforded a mixture of three dimeric diamides in 17 % yield over the three steps from alcohol 11.…”

Total Synthesis of Kingianin A

“…2 They are reported to have low- to midmicromolar binding to the antiapoptotic protein Bcl-xL. 1a The antiapoptotic Bcl proteins are considered to be valid drug targets for the treatment of cancer, particularly lymphomas, leukemias, and small cell lung cancers. 3,4 …”

Bioinspired Synthesis of (−)‐PF‐1018

“…It should be noted that the endriandric acids and kingianin A were isolated as racemates and spontaneously form from their achiral polyene precursors 1 and 3 . By contrast, PF‐1018 was isolated as a single enantiomer and diastereomer.…”

“…It should be noted that the endriandric acids and kingianin A were isolated as racemates and spontaneously form from their achiral polyene precursors 1 and 3. [1,4] By contrast, PF-1018 was isolated as a single enantiomer and diastereomer. It seems unlikely that the existing stereocenter in the hypothetical precursor 6 would govern the diastereoselectivity of the initial 8p electrocyclization.…”

“…[1][2][3] In the case of kingianin A, the electrocyclization cascade yields cyclooctatriene 4 and then bicyclo[4.2.0]octadiene 5, which engages in an intermolecular Diels-Alder dimerization (Scheme 1 B). [4,5] Other examples that have been validated by biomimetic or bioinspired synthesis include ocellapyrone A, [6] where the electrocyclizations are followed by an intramolecular hetero-Diels-Alder reaction, and orinocin, [7] where they are followed by a retro-[2+2] cycloaddition, resulting in "polyene splicing".…”