Total Synthesis of (+)-Arborisidine.

The first total synthesis of arborisidine, a unique Kopsia indole alkaloid possessing a fully substituted cyclohexanone ring system with two quaternary carbons, has been achieved in seven steps in racemic format from tryptamine and in nine steps in asymmetric format from d-tryptophan methyl ester. Key elements of the design include a carefully orchestrated decyanation protocol to finalize the asymmetric formation of an aza-quaternary center that is challenging to access in optically active format via direct Pictet-Spengler cyclizations with tryptamine, a metal-promoted 6- endo-dig cyclization of an enyne to establish the second core quaternary center, and regiospecific functionalizations of the resultant complex diene to finalize the target structure. The distinct and efficient nature of the developed solution is highlighted by several unsuccessful approaches and unexpected rearrangements.

A 7-Step Formal Asymmetric Total Synthesis of Strictamine via an Asymmetric Propargylation and Metal-Mediated Cyclization.

Herein is shown how a novel catalytic asymmetric propargylation of 3,4-dihydro-ß-carboline, followed by a designed Au(I)/Ag(I)-mediated 6-endo-dig cyclization, can directly deliver the indolenine-fused methanoquinolizidine core of the akuammiline alkaloid strictamine in its native oxidation state, ultimately achieving a 7-step formal asymmetric total synthesis. Also demonstrated are how the cyclization products can rearrange into vincorine-type skeletons and a further use for the developed propargylation with the first catalytic asymmetric total synthesis of decarbomethoxydihydrogambirtannine.

The Enantioselective Total Synthesis of Exochomine.

Molecules that possess fully substituted chiral centers are often challenging to construct, particularly if those centers connect two seemingly different halves or include a nitrogen atom. Herein, we describe an efficient approach to a molecule that combines both challenges in a single center in the form of exochomine. Failures in direct coupling led to a design fueled by highly specific reaction conditions for several steps and the development of an improved protocol for 1,4-reduction in a hindered context where numerous side reactions were possible. These chemoselective solutions should have value to other problems. Challenges in obtaining matching spectral data for the synthesized natural product are also discussed.

Studies towards the synthesis of halomon: asymmetric hexafunctionalisation of myrcene.

A novel dihydroxylation-dibromination-dihydroxylation sequence employing in situ protection of diols as boronate esters during the dihydroxylation reactions provides the first enantiomerically pure hexafunctionalised myrcene derivative. This concise four-step asymmetric sequence provides an advanced intermediate for the targeted synthesis of halomon via stereospecific transformations, where both stereogenic centres of the natural product have been set.