Selective Glycan Labeling of Mannose-Containing Glycolipids in Mycobacteria.

() is one of history's most successful human pathogens. By subverting typical immune responses, can persist within a host until conditions become favorable for growth and proliferation. Virulence factors that enable mycobacteria to modulate host immune systems include a suite of mannose-containing glycolipids: phosphatidylinositol mannosides, lipomannan, and lipoarabinomannan (LAM).

Total Synthesis of (+)-Shearilicine.

Herein we report the first total synthesis of the indole diterpenoid natural product shearilicine by an 11-step sequence via a generalizable precursor to the highly oxidized subclass of indole diterpenoids. A native chiral auxiliary strategy was employed to access the target molecule in an enantiospecific fashion. The formation of the key carbazole substructure was achieved through a mild intramolecular Heck cyclization, wherein a computational study revealed noncovalent substrate-ligand and ligand-ligand interactions that promoted migratory insertion.

Biosynthetic incorporation for visualizing bacterial glycans.

Cell-surface glycans are central to many biological processes, yet methods for their site-selective modification are limited. Strategies for interrogating the structure and function of proteins have been enabled by chemoselective reactions of sidechain functionality for covalent modification, capture, or imaging. However, unlike protein sidechains, glycan building blocks lack distinguishing reactivity.

Biosynthetic Glycan Labeling.

Glycans are ubiquitous and play important biological roles, yet chemical methods for probing their structure and function within cells remain limited. Strategies for studying other biomacromolecules, such as proteins, often exploit chemoselective reactions for covalent modification, capture, or imaging. Unlike amino acids that constitute proteins, glycan building blocks lack distinguishing reactivity because they are composed primarily of polyol isomers.

Total Synthesis of Paspaline A and Emindole PB Enabled by Computational Augmentation of a Transform-Guided Retrosynthetic Strategy.

We report the total syntheses of two indole diterpenoid natural products, paspaline A and emindole PB. Paspaline A is synthesized in a 9-step sequence from commercially available materials. The first total synthesis of emindole PB is accomplished in 13 steps and confirms a previously ambiguous structural assignment.

Vinylogous acyl triflates as an entry point to α,β-disubstituted cyclic enones via Suzuki-Miyaura cross-coupling.

An alternative protocol for the B-alkyl Suzuki-Miyaura reaction to produce cyclic α,β-disubstituted enones is reported. The use of β-triflyl enones as coupling partners in lieu of their halogenated analogs provides enhanced substrate stability to light and chromatography without adversely affecting reactivity. This protocol allows efficient access to the synthetically challenging α,β-disubstituted enone motif under mild conditions.

Methods Utilizing First-Row Transition Metals in Natural Product Total Synthesis.

First-row transition-metal-mediated reactions constitute an important and growing area of research due to the low cost, low toxicity, and exceptional synthetic versatility of these metals. Currently, there is considerable effort to replace existing precious-metal-catalyzed reactions with first-row analogs. More importantly, there are a plethora of unique transformations mediated by first-row metals, which have no classical second- or third-row counterpart.