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Herein, we describe the efficient, diastereoselective syntheses of the iminosugars 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) 1b, lentiginosine 3a, and the seven stereoisomers of each of these iminosugars starting from 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 with yields ranging from 38 % to 68 % for the DAB and isomers 1a-1h and from 44 % to 89 % for the lentiginosine and isomers 3a-3h. We also report the syntheses of the eight stereoisomers of the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 from commercially available sugars. Key to the iminosugar syntheses is a single multistep reaction that converts the 4-benzoyl-6-deoxy-6-iodoglycopyranosides 47 to a vinyl pyrrolidine through a one-pot zinc mediated reductive elimination, followed by a reductive amination and finally an intramolecular nucleophilic substitution. Strategic selection of the amine utilized in the reductive amination and the functionalization of the intermediate carbon-carbon double bond provides access to a vast array of iminosugars., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Louis J. Liotta reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We report the first evidence of GEX1A, a polyketide known to modulate alternative pre-mRNA splicing, as a potential treatment for Niemann-Pick type C disease. GEX1A was isolated from its producing organism, Streptomyces chromofuscus, and screened in NPC1 mutant cells alongside several semisynthetic analogues. We found that GEX1A and analogues are capable of restoring cholesterol trafficking in NPC1 mutant fibroblasts, as well as altering the expression of NPC1 isoforms detected by Western blot. These results, along with the compound's favorable pharmacokinetic properties, highlight the potential of spliceosome-targeting scaffolds such as GEX1A for the treatment of genetic diseases.

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry (MS) techniques are well-suited to high-throughput characterization of NP, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access knowledge base for community-wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of 'living data' through continuous reanalysis of deposited data.