The fungus Penicillium verruculosum Peyronel, isolated from green peanuts, produces a toxic metabolite verruculotoxin with an LD50 of 20 mg/kg (oral, 1-day-old cockerel), characterized by ataxia, prostration, and complete lack of muscular coordination. Previous preliminary work reported its isolation procedures and spectral data (IR, NMR, MS, UV), and we now report its absolute stereostructure via X-ray diffraction analysis and synthesis. X-ray analysis showed space group P2₁2₁2₁ with unit cell parameters a=14.340(1) Å, b=12.211(1) Å, c=7.896(1) Å, one C₁₈H₂₀N₂O molecule per asymmetric unit, and refinement to R=0.036. Verruculotoxin represents the first naturally occurring octahydro-2H-pyrido[1,2-a]pyrazine system, with a flattened chair piperazine ring (axial benzyl group), chair piperidine ring, trans ring junction at puckered bridgehead N(5), planar phenyl group, and no hydrogen bonds. Synthesis from L-phenylalanine involved formation of phenylalinol, reaction with methyl picolinate to amide, conversion to chloride, reflux to chloride salt, and hydrogenation to yield verruculotoxin (major ~80%) and its C(10) epimer; the major product matched natural verruculotoxin in physical/biological properties, while the epimer was inactive. Absolute configuration was confirmed by positive Cotton effect (220 nm), consistent with L-amino acid biogenesis. Additionally, for Schiff base hydrolysis (e.g., 2,2,2-trifluoro-N-(3-methyl-2-cyclohexenylidene)ethylamine in dioxane-water), lowering solvent polarity accelerates the reaction, and a synergism exists between general base catalysis and reduced solvent polarity. The hydrolysis rate in 90% dioxane (0.01 N HCl) was 18-fold higher than in pure water, with a 180-fold higher actual rate constant for water attack on the protonated Schiff base (accounting for lower water concentration). This synergism may explain enzymatic rates, as enzymes can utilize both effects to enhance reaction speed.