A Pyridine Dearomatization Approach for the Gram Scale Synthesis of (±)-Sparteine.

Both enantiomers of sparteine have suffered from pricing and supply chain variability, which has inspired efforts toward efficient chemical synthesis. Here, we build upon our reported synthesis of the matrine-type lupin alkaloids in order to synthesize (±)-sparteine. Specifically, selective quenching of the cyclization between glutaryl chloride and pyridine with methanol provides a functionalized quinolizidine core that was elaborated to (±)-sparteine in six additional steps on gram scale.

A convergent fragment coupling strategy to access quaternary stereogenic centers.

The formation of quaternary stereogenic centers convergent fragment coupling is a longstanding challenge in organic synthesis. Here, we report a strategy for the formation of quaternary stereogenic centers in polycyclic systems based upon the semi-pinacol reaction. In the key transformation, two fragments of a similar size and complexity are joined by a 1,2-addition of an alkenyl lithium to an epoxy ketone, and the resulting epoxy silyl ether undergoes a semi-pinacol rearrangement catalyzed by -(trimethylsilyl)bis(trifluoromethanesulfonyl)imide (TMSNTf) or trimethylsilyl trifluoromethanesulfonate (TMSOTf).

A Pyridine Dearomatization Approach to the Matrine-Type Lupin Alkaloids.

(+)-Matrine and (+)-isomatrine are tetracyclic alkaloids isolated from the plant , the roots of which are used in traditional Chinese medicine. Biosynthetically, these alkaloids are proposed to derive from three molecules of (-)-lysine via the intermediacy of the unstable cyclic imine Δ-piperidine. Inspired by the biosynthesis, a new dearomative annulation reaction has been developed that leverages pyridine as a stable surrogate for Δ-piperidine.

Total Synthesis of Isodihydrokoumine, (19 Z)-Taberpsychine, and (4 R)-Isodihydroukoumine N-Oxide.

We report the total synthesis of the natural products isodihydrokoumine and (19 Z)-taberpsychine in 11 steps each and (4 R)-isodihydrokoumine N-oxide in 12 steps from commercially available starting materials. The key reactions include an intramolecular [3 + 2] nitrone cycloaddition and Lewis acid mediated cyclizations of a common intermediate to provide the core structures of either taberpsychine or isodihydrokoumine.

N-β-Methylamino-L-Alanine and Its Naturally Occurring Isomers in Cyanobacterial Blooms in Lake Winnipeg.

Cyanobacterial blooms have affected Lake Winnipeg since the mid-1990s due to an increased phosphorus loading into the lake, which has been exacerbated by stressors such as climate change and eutrophication. Aquatic ecosystems involving cyanobacteria have been found to contain N-β-methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB), non-protein amino acids that are associated with neurodegenerative disease, as well as two of the naturally occurring isomers, N-2(amino)ethylglycine (AEG) and β-amino-N-methylalanine (BAMA). We hypothesized that the cyanobacterial bloom in Lake Winnipeg produces BMAA and/or its naturally occurring isomers.