New Entries in Organocatalysts from an Alkaloid Library; Development of Aminal Catalysis for a Michael Reaction Based on Calycanthine.

Natural products have historically been actively evaluated for their biological activity in the development of pharmaceuticals, while their evaluation as asymmetric catalysts has rarely been explored. In this study, we evaluated the catalytic activity of the natural product library. Three naturally occurring alkaloids, gardnerine, spiradine A, and calycanthine, were found to catalyze an asymmetric Michael reaction using oxindole and nitrostyrene.

Synthesis of Substituted 1,2-Dihydroisoquinolines by Palladium-Catalyzed Cascade Cyclization-Coupling of Trisubstituted Allenamides with Arylboronic Acids.

1,2-Dihydroisoquinolines are important compounds due to their biological and medicinal activities, and numerous approaches to their synthesis have been reported. Recently, we reported a facile synthesis of trisubstituted allenamides via -acetylation followed by DBU-promoted isomerization, where various substituted allenamides were conveniently synthesized from readily available propargylamines with high efficiency. In light of this research background, we focused on the utility of this methodology for the synthesis of substituted 1,2-dihydroisoquinolines.

Divergent Total Syntheses of Hetero-Oligomeric Iridoid Glycosides.

Divergent total syntheses of the hetero-oligomeric iridoid glycosides mainly found in were achieved. Thus, loganin (), which is important as a monomer unit, was efficiently synthesized by stereoselective reductive cyclization using secologanin () as a substrate. Sequential condensation reactions of derivatives of and as monomer units led to the first enantioselective total syntheses of the heterooligomers cantleyoside, ()-aldosecologanin, dipsaperine, (3, 5)-5-carboxyvincosidic acid 22-loganin ester, and dipsanoside A.

Asymmetric Total Synthesis and Structure Elucidation of Huperzine H.

A first asymmetric total synthesis of huperzine H has been achieved in a 12% overall yield from commercially available (+)-pulegone. The key steps of this synthesis include a highly diastereoselective Mukaiyama-Michael addition reaction of a pyrrole bearing a silyl enol ether and an intramolecular S2 cyclization reaction with iodinated pyrrole acting as an effective nucleophile for the formation of the nine-membered ring. As a result, the relative and absolute stereochemistry of huperzine H is established.

A New Organocatalytic Desymmetrization Reaction Enables the Enantioselective Total Synthesis of Madangamine E.

The enantioselective total synthesis of madangamine E has been completed in 30 steps, enabled by a new catalytic and highly enantioselective desymmetrizing intramolecular Michael addition reaction of a prochiral ketone to a tethered -disubstituted nitroolefin. This key carbon-carbon bond forming reaction efficiently constructed a chiral bicyclic core in near-perfect enantio- and diastereo-selectivity, concurrently established three stereogenic centers, including a quaternary carbon, and proved highly scalable. Furthermore, the pathway and origins of enantioselectivity in this catalytic cyclization were probed using density functional theory (DFT) calculations, which revealed the crucial substrate/catalyst interactions in the enantio-determining step.

Correction: Enantioselective total synthesis of the unnatural enantiomer of quinine.

[This corrects the article DOI: 10.1039/C9SC03879E.].

Enantioselective total synthesis of the unnatural enantiomer of quinine.

A practical enantioselective total synthesis of the unnatural (+)-quinine and (-)-9--quinine enantiomers, which are important organocatalysts, is reported. The key transformation is a successive organocatalytic formal aza [3 + 3] cycloaddition/Strecker-type cyanation reaction to form an optically active tetrasubstituted piperidine derivative. This organocatalytic reaction proceeded in high yield and gave excellent enantiomeric excess with only 0.

Alkaloid Synthesis Using Organocatalysts.

This chapter covers the literature since the advent, in the 21st century, of total syntheses of alkaloids using enantio- or diastereoselective organocatalytic reactions to construct the alkaloid scaffolds. The details of these alkaloid syntheses are described separately for each basic skeleton, including indole, indoline, oxindole, and piperidine alkaloids.

Total syntheses and stereochemical reassignments of mollenines A and B.

Total syntheses of prenylated pyrrolidinoindoline alkaloids, (-)-mollenines A [(-)-1'] and B (2'), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S,14S,16S by analysis of spectroscopic data and chemical syntheses with different approaches along with the comparison of calculated and experimental ECD spectra. In addition, a thermodynamically controlled epimerization reaction on the dioxomorpholine ring was observed in our synthesis.

Bioinspired Indole Prenylation Reactions in Water.

Isoprene units derived from dimethylallyl diphosphate (DMAPP) are an important motif in many natural products including terpenoids, carotenoids, steroids, and natural rubber. Understanding the chemical characteristics of DMAPP is an important topic in natural products chemistry, organic chemistry, and biochemistry. We have developed a direct bioinspired indole prenylation reaction using DMAPP or its equivalents as the electrophile in homogeneous aqueous acidic media in the absence of enzyme to provide prenylated indole products.

Alkaloid synthesis using chiral secondary amine organocatalysts.

Over the last decade, several excellent enantioselective total syntheses of important alkaloids using asymmetric reactions mediated by chiral secondary amine organocatalysts as a key step have been accomplished. This perspective article examines the full strategies of these alkaloid syntheses, especially the application of the organocatalytic reaction to construct the alkaloid scaffolds.

Efficient Organocatalytic Construction of C4-Alkyl Substituted Piperidines and Their Application to the Synthesis of (+)-α-Skytanthine.

Chiral piperidines which contain an alkyl group at C4 positions are one of the important architectures because it is appeared in several natural products. An efficient protocol for the preparation of C4-alkyl substituted chiral piperidines using secondary amine catalyzed formal aza [3+3] cycloaddition reaction with aliphatic α,β-unsaturated aldehydes and thiomalonamate derivatives is reported. In our reaction system, thiomalonamate is an excellent nucleophile and the addition of suitable acid and its amount is an important factor for the acceleration effect in organocatalytic reaction.

A carbaboranylmercuric salt catalyzed reaction; highly regioselective cycloisomerization of 1,3-dienes.

The combination of carbaboranylmercuric chloride (new type of bulky Lewis acid) and silver triflate efficiently catalyzes cycloisomerization of 1,3-dienes at room temperature. The catalytic system gives allyl-substituted azacycles and cycloalkanes in excellent yields with high to complete regioselectivity.