Polycavernoside A: the Prins macrocyclization approach.

The Primed In Situ (PRINS) Technique: An Alternative Approach for Preimplantation Chromosomal Diagnosis

Effects of a synthetic analog of polycavernoside A on human neuroblastoma cells.

BACKGROUND Polycavernoside A is a glycosidic marine toxin first extracted from the red alga Polycavernosa tsudai in 1991 when 3 people died after the ingestion of this food. Polycavernoside A is an interesting molecule because of its complex macrolide structure and strong bioactivity. However, the target site of this toxin has not been characterized. METHODS We studied the effects of a synthe...

Total synthesis and stereochemical reassignment of mandelalide A.

The total synthesis of the tunicate metabolite mandelalide A and the correction of its originally assigned stereochemistry are reported. Key features of the convergent, fully stereocontrolled route include the use of a Prins cyclization for the diastereoselective construction of the tetrahydropyran subunit, Rychnovsky-Bartlett cyclization for the preparation of the tetrahydrofuran moiety, Suzuk...

Computational Macrocyclization: From de novo Macrocycle Generation to Binding Affinity Estimation

Macrocycles play an increasing role in drug discovery, but their synthesis is often demanding. Computational tools that suggest macrocyclization based on a known binding mode and that estimate the binding affinity of these macrocycles could have a substantial impact on the medicinal chemistry design process. For both tasks, we established a workflow with high practical value. For five diverse p...

Designed, Synthetically Accessible Bryostatin Analogues Potently Induce Activation of Latent HIV Reservoirs in vitro

Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer's disease and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically relevant derivatives, and side effects. Here, we address these problems through the step-economical syntheses of seven members ...