Lycibarbarines A-C (1-3) are spiroketal alkaloids isolated in 2021 by Chen et al from the fruits of Lycium barbarum, also known as goji berries (Scheme 1). Goji berries have been used in traditional Chinese medicine for over 2000 years for the treatment of age-related conditions, including improved eyesight, improved liver and kidney functions, as well as antioxidant, immunomodulating, and antitumor activity. Lycibarbarines A (1) and C (3) demonstrated neuroprotective activity by reduction of apoptosis in corticosterone-injured PC12 cells, and were found to reduce the expression levels of cleaved caspase-3 and caspase-9. Lycibarbarines A-C (1-3) possess a unique tetracyclic structure, consisting of tetrahydroquinoline and spiro-fused oxazine-sugar spiroketal subunits. The oxazine-sugar spiroketal moiety is similar to the pyrrolomorpholine spiroketal compound class, all of which demonstrate inhibition of high-glucose induced reactive oxygen species production in mesangial cells. Our group has had a longstanding interest in spiroketalcontaining natural products, due to their attractive bioactivities, and the privileged nature of the spiroketal scaffold. We have accomplished the total synthesis of several spiroketal-containing natural products, including acortatarin A and pollenopyrroside A, which share structural similarities with 1-3. We were intrigued by the lycibarbarines because they appeared to represent kinetic [5,6]-and thermodynamic [6,6]spiroketal products derived from the same oxocarbenium precursor 4 (Scheme 1). This suggested 1-3 would likely interconvert under acidic conditions, or at least that the kinetic products (1 and 2) could potentially be isomerised to the thermodynamically-favored lycibarbarine C (3). This would be in line with the known tendency of spiroketals to epimerise or isomerise under mildly acidic conditions, to the thermodynamically favored isomer, stabilised by the anomeric effect, minimisation of steric interactions, and intramolecular hydrogen bonding effects. Whilst various synthetic strategies have been developed to access non-thermodynamic spiroketal frameworks, such scaffolds remain labile to isomerisation under acidic conditions. Scheme 1. Lycibarbarines A-C (1-3) and access from the same oxocarbenium precursor 4.