A total synthesis of the Aspidosperma alkaloids (+)-fendleridine (1) and (+)-1-acetylaspidoalbidine (2) is detailed, providing access to both enantiomers of the natural products and establishing their absolute configuration. Central to the synthetic approach is a powerful intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of a 1,3,4-oxadiazole in which the pentacyclic skeleton and all the stereochemistry of the natural products are assembled in a reaction that forms three rings, four C-C bonds, five stereogenic centers including three contiguous quaternary centers, and introduces the correct oxidation state at C19 in a single synthetic operation. The final tetrahydrofuran bridge is subsequently installed in one-step, enlisting an intramolecular alcohol addition to an iminium ion generated by nitrogen assisted opening of the cycloadduct oxido bridge, with a modification that permits release of useful functionality (a ketone) at the cleavage termini.

We have explored various different machine learning (ML) approaches for forecasting tsunami amplitudes at a set of forecast points, based on hypothetical short-time observations at one or more observation points. As a case study, we chose an observation point near the entrance of the Strait of Juan de Fuca, and two forecast points in the Salish Sea, one in Discovery Bay and the other in Admiralty Inlet, the waterway leading to southern Puget Sound. One ML approach considered is to train a support vector machine (SVM) to predict the maximum amplitude at the forecast points. We also explored the use of two deep convolutional neural networks, a denoising autoencoder (DAE) and a variational autoencoder (VAE) to predict the full time se-

Synthesis of bacterial cell wall peptidoglycan requires glycosyltransferase enzymes that transfer the disaccharide-peptide from lipid II onto the growing glycan chain. The polymerization of the glycan chain precedes cross-linking by penicillin-binding proteins and is essential for growth for key bacterial pathogens. As such, bacterial cell wall glycosyltransferases are an attractive target for antibiotic drug discovery. However, significant challenges to the development of inhibitors for these targets include the development of suitable assays and chemical matter that is suited to the nature of the binding site. We developed glycosyltransferase enzymatic activity and binding assays using the natural products moenomycin and vancomycin as model inhibitors. In addition, we designed a library of disaccharide compounds based on the minimum moenomycin fragment with peptidoglycan glycosyltransferase inhibitory activity and based on a more drug-like and synthetically versatile disaccharide building block. A subset of these disaccharide compounds bound and inhibited the glycosyltransferase enzymes, and these compounds could serve as chemical entry points for antibiotic development.