Dimerization and comments on the reactivity of homophthalic anhydride.

Homophthalic anhydride (HPA) dimerizes under the influence of base to provide, sequentially, the (3-4')-C-acyl dimer, a pair of chiral diastereomeric bis(lactones), 3-(2-carboxybenzyl)isocoumarin-4-carboxylic acid, and finally, 3-(2-carboxybenzyl)isocoumarin. The structures of the bis(lactones) were misassigned in 1970 based on the (presumed) cis thermal decarboxylative elimination reaction of the lower melting one. The preferred pathway should be trans-anti, however, and crystallographic analysis of one of the bis(lactones) reverses the earlier assignment. The formal cycloaddition reaction of HPA with imines occurs in preference to HPA dimerization; the mechanistic implications of this reactivity difference are discussed.

Closing the Door to Lost Earnings Under the National Childhood Vaccine Injury Act of 1986.

After a wave of lawsuits against vaccine manufacturers hindered the profitability and production of life-saving vaccines, Congress enacted The National Childhood Vaccine Injury Act of 1986. The Act offers an incentive for individuals to get vaccinated in order to mitigate the population's exposure to disease, while encouraging the continued production of these serums by pharmaceutical companies. Although imperfect, the Vaccine Act fosters promise in filtering out frivolous claims and,provides a central route for due process to the individuals who suffer from a vaccine-related injury. By removing a potential state tort issue to the Federal Circuit, Congress created a reasonably justified avenue for the recovery of damages for injuries and adverse reactions to vaccines. However, this is not to say that the Act can't still be improved. Currently, the Act is silent on whether the death of a child from a vaccine-related injury, before a compensation decision is rendered, should bar the family from recovering for the child's lost earnings. Unless the victim demonstrates a stable source of income that they would have earned had their lives not been interrupted by the adverse reaction to the vaccine, the holding that a minor child may not recover for lost earnings is defensible. However, Congress should revise the statute to issue guidance to clarify its ambiguity. Under the current compensation regime, the standard is too arbitrary to decide that a child who dies before reaching the majority age of 18 has no earning potential. Any line Congress or the Supreme Court tries to draw will be arbitrary, but from an economic, policy, and legal perspective clarity and guidance can be offered to maintain greater flexibility through a case-by-case analysis and by applying the modern minimum wage in reference to the child's age. Independent from future earnings awards, Vaccine Act compensation should be amended to increase the cap on these damages to account for inflation since the Act's inception in 1986, to the value of the dollar almost 30 years later. It has been almost three decades since the Act's implementation with no revisions. It is time to modernize the Vaccine Injury Act to better calibrate the amount of damages awarded to the victims of a rare vaccine-related injury.

N-methylimidazole promotes the reaction of homophthalic anhydride with imines.

The addition of N-methylimidazole (NMI) to the reaction of homophthalic anhydride with imines such as pyridine-3-carboxaldehyde-N-trifluoroethylimine (9) reduces the amount of elimination byproduct and improves the yield of the formal cycloadduct, tetrahydroisoquinolonic carboxylate 10. Carboxanilides of such compounds are of interest as potential antimalarial agents. A mechanism that rationalizes the role of NMI is proposed, and a gram-scale procedure for the synthesis and resolution of 10 is also described.