The total synthesis of the atypical diterpene alkaloid thelepogine is reported. Our pathway features the asymmetric construction of a carbotricyclic intermediate that undergoes a 2,3-Wittig–Still rear...

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A short and diastereoselective synthesis of stephadiamine is presented. The carbocyclic framework of the alkaloid was built in the opening step through a homoconjugate addition–Wittig olefination cascade with a modified Schweizer–Fuchs cyclopropyl phosphonium salt. The challenging aza[4.3.3]propellane was subsequently installed through a vinylogous substitution of an allylic hydroxy group with a primary amine that was developed for the purposes of the synthesis. After a series of oxidations, a second α-tertiary amine was introduced through a diastereoselective Strecker reaction, thus establishing the syn-diamine motif. Finally, an undesired retro-Strecker pathway was circumvented by using an azide functionality to mask the primary amine during a late-stage lactonization, thus enabling the completion of the synthesis in 12 steps.

We report progress toward the asymmetric total synthesis of altemicidin, a monoterpene alkaloid featuring a 6-azatetrahydroindane core. A diastereoselective 1,3-dipolar cycloaddition with TMS-diazomethane enabled the construction of a key pyrazoline intermediate. Computational analysis (EDA/NCI) revealed attractive London dispersion forces as the origin of the unexpected stereoselectivity. An effective method to convert the initial silylated 1-pyrazoline into a stable 2-pyrazoline was developed. Selective reductive trifluoroacetylation and SmI2-mediated N–N bond cleavage afforded a 1,3-diamine suitable for further functionalization.

Vitamin D exhibits complex and cell-specific biological effects in multiple tissues via activation of the ligand-sensing transcription factor vitamin D receptor (VDR). The photo-switchable vitamin D ...

A first-in-human phase 1 trial shows that intravitreal photoswitch therapy can be administered safely in advanced retinitis pigmentosa, with exploratory signals compatible with light responsiveness fo...

Cholesterol is ubiquitous in biology, shaping membrane properties and serving as a biosynthetic precursor for essential signaling molecules and hormones─and, in some contexts, acting as a signaling mo...

Cycloadditions are among the most powerful reactions for constructing molecular complexity. The archetypal example is the [4 + 2] (Diels–Alder) cycloaddition, which efficiently furnishes cyclohexene d...

Translational Psychiatry - A prodrug targeting CIM6P/IGF2R enhances memory in healthy mice and reverses deficits in an Angelman syndrome mouse model

The lipid composition of cellular membranes is highly dynamic and undergoes continuous remodeling, affecting the biophysical properties critical to biological function. Here, we introduce an optical a...

Facilitating different chemistries between the rare earth (RE = La–Lu, Sc, Y) ions is of significant interest for their separations. While the bulk of attention has been on maximizing the small differ...

Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum…

A concise and convergent synthesis of the isosteroidal alkaloids veratramine and 20-iso-veratramine has been accomplished. A Horner–Wadsworth–Emmons olefination joins two chiral building blocks of app...

A concise synthesis of the complex diterpene azorellolide, inspired by speculations on biosynthetic cationic cascades, is presented. The approach, guided by computation, relies on the intramolecular interception of a cyclopropylcarbinyl cation by an appended carboxylate. The successful execution of this strategy was achieved through acid-catalyzed isomerization of a β-lactone in competition with a type I dyotropic rearrangement.