New One-Pot Methodologies for the Modification or Synthesis of Alkaloid Scaffolds

Abstract

There are several avenues by which promising bioactive natural products can be produced in sufficient quantities to enable lead optimization and medicinal chemistry studies. The total synthesis of natural products is an important, but sometimes difficult, approach and requires the development of innovative synthetic methodologies to simplify the synthesis of complex molecules. Various classes of natural product alkaloids are both common and widely distributed in plants, bacteria, fungi, insects and marine organisms. This mini-review will discuss the scope, mechanistic insights and enantioselectivity aspects of selected examples of recently developed one-pot methods that have been published in 2009 for the synthesis of substituted piperidines, quinolizidines, pyrrolidines, hexahydropyrrolizines, octahydroindolizines and γ-lactams. In addition, progress on the synthesis of β-carboline (manzamine) alkaloids will also be discussed.

GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS

“…Cell survival was determined in parallel by measuring LDH release. Manzamine A constitutes a promising scaffold from which more potent and selective GSK-3 inhibitors could be designed as potential therapeutic agents for the treatment of diseases mediated by GSK-3 such as the AD (Wahba and Hamann, 2011 ). Recently a potential binding site of manzamine A with GSK-3 was identified, and this will provide new directions in substrate competitive drug design (Peng et al, 2011 ).…”

Ring expansions of 1-azabicyclo[n.1.0]alkanes. Recent developments

“…Ring opening of 1, 4]oxazine 62a (X = O) with HBr gives the product 63a of N-C1 bond scission with no trace of the ring expansion product 64a. Under the same conditions compound 64b, the product of 1,5-benzothiazepine 62b ring enlargement and sequential hydrolysis, was observed and isolated in 5% yield (Scheme 14).…”

“…Their synthesis, properties, biological activity and isolation from the natural products are well-documented. 1a-d Several recent reviews have been published covering pharmaceutically active compounds, 2 spiro-derivatives, 3a-b marine alkaloids, 4 iminosugar di-and oligosaccharides, 5a-b and alkaloid lipids. 6 Advances in synthetic methods include catalytic asymmetric aza Diels-Alder reactions, 7 benzotriazole mediated syntheses, 8 asymmetric synthesis, 9a-b and cyclization of allylsilyl-substituted N-acyliminium and iminium ions.…”

Asymmetric and Site-Selective [3 + 2]-Annulations for the Synthesis of High-Value Bicyclic Lactams

“…4 Successful implementation of these dual focus strategies—addressing both chirality and complexity—can provide very easy and effective access to key targets as we exemplify herein. 5 …”