The first total synthesis of the cytotoxic marine metabolite agelastatin A (1) has been achieved in about 14 steps performed in 12 operations in approximately 7% overall yield starting from cyclopentadiene. Hetero Diels−Alder cycloaddition of cyclopentadiene with N-sulfinyl methyl carbamate (7) afforded cycloadduct 8, which without purification was converted to allylic sulfoxide 9 and then by a [2,3]-sigmatropic rearrangement into bicyclic oxazolidinone 11. The C-5a nitrogen was introduced into the oxazolidinone Boc derivative 16 by a Sharpless/Kresze allylic amination with SES sulfodiimide 12c. Palladium-promoted cyclization of 2-acyl pyrroles 20 and 21 via a π-allylpalladium intermediate 22 led to ABC-tricycles 23 and 24, respectively. A hydroxyl urea D-ring model system was constructed by hydroborating 24, leading eventually to keto amide 31 and then to tetracycle 33. A modified strategy was developed for synthesis of the pivotal tricyclic ketone 58, involving as key steps a chemoselective hydrolysis of N-Boc oxazolidinone 54 and an internal conjugate addition of pyrrolo cyclopentenone 57. A TMS group was used as a convenient substitute for the C-1 bromine substituent of agelastatin A, and thus silylpyrrole 58 could be converted to bromopyrrole 59. Finally, the D-ring could be annulated onto an α-amino ketone derived from 59 using methyl isocycanate, providing racemic agelastatin A (1).

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Numerous studies suggest critical dynamics may play a role in information processing and task performance in biological systems. However, studying critical dynamics in these systems can be challenging due to many confounding biological variables that limit access to the physical processes underpinning critical dynamics. Here we offer a perspective on the use of abiotic, neuromorphic nanowire networks as a means to investigate critical dynamics in complex adaptive systems. Neuromorphic nanowire networks are composed of metallic nanowires and possess metal-insulator-metal junctions. These networks self-assemble into a highly interconnected, variable-density structure and exhibit nonlinear electrical switching properties and information processing capabilities. We highlight key dynamical characteristics observed in neuromorphic nanowire networks, including persistent fluctuations in conductivity with power law distributions, hysteresis, chaotic attractor dynamics, and avalanche criticality. We posit that neuromorphic nanowire networks can function effectively as tunable abiotic physical systems for studying critical dynamics and leveraging criticality for computation.

2‐Trimethylsilylethanesulfonyl chloride (SES‐Cl) intermediate: sodium β‐trimethylsilylethanesulfonate product: 2‐Trimethylsilylethylsulfonyl chloride (2)

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