Molecular mechanisms of inverse agonism via κ-opioid receptor-G protein complexes.

Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex formation, while antagonists prevent G protein coupling. However, many GPCRs exhibit basal activity, allowing G protein association without an agonist.

Synthesis of psychotropic alkaloids from .

Efficient syntheses of valuable natural products open gateways from kind learning environments to wicked worlds, where long-term, interdisciplinary research questions can be asked and answered. In this Perspective, we discuss the (GB) alkaloids, metabolites of a rainforest canopy tree that exhibit potent but poorly understood effects in humans, including accounts of hallucination. Recent syntheses from our group have opened up GB alkaloid chemical space for investigation by way of new cross-coupling reactions and gram-scale target production.

Synthesis and target annotation of the alkaloid GB18.

Ingestion of alkaloid metabolites from the bark of Galbulimima (GB) sp. leads to psychotropic and excitatory effects in humans. Limited, variable supply of GB alkaloids, however, has impeded their biological exploration and clinical development.

Natural Product Synthesis through the Lens of Informatics.

Retrosynthetic analysis emerged in the 1960s as a teaching tool with profound implications. Its educational value can be appreciated by a glance at total synthesis manuscripts over 50 years later, most of which contain a retrosynthesis on page one. Its vision extended to computer language-a pioneering idea in the 20th century that continues to expand the frontiers today.

Total Synthesis and Stereochemical Confirmation of Heliolactone.

Until now, the relative stereochemistry of the noncanonical strigolactone, heliolactone, has remained ambiguous. The total synthesis of heliolactone is described, with the key bond-forming event being a Stille cross-coupling that relied upon a reversal of the nucleophile-electrophile coupling partners. Spectroscopic analysis of synthetic heliolactone (and other stereoisomers) and comparisons with the isolated material enabled the absolute and relative stereochemistry of heliolactone to be secured.