Impact sensitivities of energetic materials derived from easy-to-compute ab initio rate constants.

New procedures to estimate the impact sensitivity of energetic materials are derived from an earlier semiempirical model correlating the drop weight impact height h50 to the rate constant k for the propagation of the decomposition process, assumed to be the limiting step. The new models are obtained by removing step by step the empiricism in the evaluation of k. We end up with a full ab initio expression for this constant in terms of theoretical activation energies and prefactors. The resulting model casts doubt on a previously introduced assumption regarding the temperature at the reaction front. Moreover, it questions possible interpretations of semiempirical estimates. A systematic comparison against alternative methods shows that although somewhat less accurate than its earlier semiempirical version, this ab initio model shows a predictive value similar to heavily parameterized approaches. The results imply that the decomposition kinetics accounts for at least 50% of the variation in the logarithms of drop height data.

Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use.

To support clinical use, a multigram-scale process has been developed to provide 5-MeO-DMT, a psychedelic natural product found in the parotid gland secretions of the toad, Incilius alvarius. Several synthetic routes were initially explored, and the selected process featured an optimized Fischer indole reaction to 5-MeO-DMT freebase in high-yield, from which the 1:1 succinate salt was produced to provide 136 g of crystalline active pharmaceutical ingredient (API) with 99.86% peak area by high-performance liquid chromatography (HPLC) and a net yield of 49%. The report provides in-process monitoring, validated analytical methods, impurity formation and removal, and solid-state characterization of the API essential for subsequent clinical development.

Synthesis of α-alkylated γ-butyrolactones with concomitant anhydride kinetic resolution using a sulfamide-based catalyst.

The Kinetic Resolution (KR) of α-alkylated enolisable disubstituted anhydrides has been shown to be possible for the first time. In the presence of an ad hoc designed novel class of bifunctional sulfamide organocatalyst, a regio-, diastereo- and enantioselective cycloaddition reaction between the enolisable anhydride and benzaldehydes provides densely functionalised γ-butyrolactones in one pot (up to 19 : 1 dr, 94% ee) with control over three contiguous stereocentres. The concomitant resolution of the starting material anhydride, provides access to a range of chiral succinate derivatives with selectivity factors up to S* = 10.5.

Dynamic kinetic resolution of bis-aryl succinic anhydrides: enantioselective synthesis of densely functionalised γ-butyrolactones.

The efficient Dynamic Kinetic Resolution (DKR) of disubstituted anhydrides has been shown to be possible for the first time. Using an ad hoc designed organocatalyst and an enantio- and diastereoselective cycloaddition process with aldehydes, stereochemically complex γ-butyrolactone derivatives can be obtained - with control over three contiguous stereocentres, one of which is all carbon quaternary.