Synthesis Of Alkaloid Natural Products Research Articles

Enantioselective Synthesis of Pyrroloindolines via Noncovalent Stabilization of Indole Radical Cations and Applications to the Synthesis of Alkaloid Natural Products.

While interest in the synthetic chemistry of radical cations continues to grow, controlling enantioselectivity in the reactions of these intermediates remains a challenge. Based on recent insights into the oxidation of tryptophan in enzymatic systems, we report a photocatalytic method for the generation of indole radical cations as hydrogen-bonded adducts with chiral phosphate anions. These noncovalent open-shell complexes can be intercepted by the stable nitroxyl radical TEMPO· to form alkoxyamine-substituted pyrroloindolines with high levels of enantioselectivity. Further elaboration of these optically enriched adducts can be achieved via a catalytic single-electron oxidation/mesolytic cleavage sequence to furnish transient carbocation intermediates that may be intercepted by a wide range of nucleophiles. Taken together, this two-step sequence provides a simple catalytic method to access a wide range of substituted pyrroloindolines in enantioenriched form via a standard experimental protocol from a common synthetic intermediate. The design, development, mechanistic study, and scope of this process are presented, as are applications of this method to the synthesis of several dimeric pyrroloindoline natural products.

ChemInform Abstract: Studies on Difficult Intramolecular Hydroaminations in the Context of Four Syntheses of Alkaloid Natural Products.

AbstractIt is found that under appropriate conditions commonly difficult intramolecular hydroamination of several internal alkenes yielding 6‐membered N‐heterocyclic ring systems can be performed successfully.

Studies on Difficult Intramolecular Hydroaminations in the Context of Four Syntheses of Alkaloid Natural Products

Examples of intramolecular alkene hydroaminations forming six-membered ring systems are rare, especially for systems in which the double bond is disubstituted. Such cyclizations have important synthetic relevance. Herein we report a systematic study of these cyclizations using recently developed Cope-type hydroamination methodologies. Difficult intramolecular alkene hydroaminations were used as key steps in syntheses of 2-epi-pumiliotoxin C, coniine, N-norreticuline and desbromoarborescidine A. This effort required the development of optimized hydroamination conditions to improve the efficiency of the cyclizations. Collectively, our results show that Cope-type cyclizations can be achieved on a variety of challenging substrates and proceed under similar conditions for both N-H and N-substituted hydroxylamines.

ChemInform Abstract: Biogenetically Inspired Syntheses of Alkaloid Natural Products

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Total Synthesis of (+)-Lyconadin A and Related Compounds via Oxidative C−N Bond Formation

The formation of carbon-nitrogen (C-N) bonds is a fundamental bond construction in organic synthesis and is indispensable for the synthesis of alkaloid natural products. In the context of the synthesis of the architecturally complex Lycopodium alkaloid lyconadin A, we have discovered a highly efficient oxidative C-N bond forming reaction that relies on the union of a nitrogen anion and a carbon anion. Empirical evidence amassed during our synthetic studies suggests that the mechanism of the C-N bond forming process encompasses polar as well as radical processes. Herein, we present our study of this novel C-N bond forming reaction and its application to the enantioselective total synthesis of lyconadin A and related derivatives.

Biogenetically inspired syntheses of alkaloid natural products

Since the synthesis of tropinone in the early 20th century, generations of chemists have looked to nature for inspiration in developing elegant syntheses of natural products. Analyzing molecules in their native context greatly enriches the chemist's understanding of nature's solution to the rapid generation of molecular complexity. In this tutorial review, we examine select examples from the alkaloid literature to highlight ways in which the close interplay of chemistry and biology have resulted in the development of elaborate biosynthetic hypotheses as well as strikingly beautiful syntheses. In addition, we present a case study on this topic through the lens of our total synthesis of (+)-11,11'-dideoxyverticillin A.

Recent Advances in the Stevens Rearrangement of Ammonium Ylides. Application to the Synthesis of Alkaloid Natural Products

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of Alkaloid Natural Products Using Solid‐Supported Reagents and Scavengers

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Alkaloid Natural Products Using Solid-Supported Reagents and Scavengers

Synthesis of Alkaloid Natural Products Using Solid-Supported Reagents and Scavengers

3 + 3] Cycloadditions and related strategies in alkaloid natural product synthesis

In this article we describe a strategically unusual approach to piperidines via formal [3 + 3] cycloaddition reactions. The scope and limitations of these processes are outlined and their employment in the synthesis of alkaloid natural products is delineated.

General strategies for the stereoselective synthesis of alkaloid natural products

Abstract

ChemInform Abstract: Studies of the Tetrathiafulvalene Mediated Radical‐Polar Crossover Reaction Directed Toward the Total Synthesis of Alkaloid Natural Products.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Studies of the tetrathiafulvalene mediated radical-polar crossover reaction directed toward the total synthesis of alkaloid natural products

The carbon skeleton of octahydro-1 H-pyrrolo[2,3- d]carbazole ( 4), a tetracylic sub-unit which is common to a wide range of alkaloid natural products has been prepared by two approaches which exploit the one-pot radical-polar crossover chemistry mediated by tetrathiafulvalene. Both approaches proceed with complete stereoselectivity.