Studies toward the total synthesis of (+)-gelsemine and synthesis of spirocyclopentaneoxindole through intramolecular Michael cyclization

During the approach to the total synthesis of (+)-gelsemine, two novel spirocyclopentaneoxindole compounds 2 and 3 were obtained. Starting from compound 9, spirocyclopentaneoxindole 3 was efficiently and unexpectedly obtained through a Boc migration-intramolecular Michael cyclization cascade procedure. This intramolecular Michael addition strategy allows conveniently access to complex spirooxindole and spirocyclopentaneoxindole derivatives.     

Asymmetric total synthesis of (+)-luciduline: toward a general approach to related Lycopodium alkaloids

As part of a research program directed toward the synthesis of Lycopodium alkaloids, a multigram scale asymmetric synthesis of intermediate 11 was achieved in 11 steps from pyridine (17). In addition to our alkene metathesis strategy, a key feature of this synthetic approach consists of a Fukuyama's Diels-Alder cycloaddition between 1,2-dihydropyridine and acrolein using MacMillan's catalyst (18) on a 50 g scale. This led to a 12-step catalytic asymmetric synthesis of (+)-luciduline (1). A broader subset of Lycopodium alkaloids could also be obtained, as demonstrated by the derivatization of 11 into advanced intermediates for the synthesis of some of these natural products.     

Intramolecular Heck cyclization to the galanthamine-type alkaloids: total synthesis of (±)-lycoramine

A novel approach towards the construction of the galanthamine skeleton was demonstrated by the total synthesis of (±)-lycoramine. The key steps include a Pd-catalyzed intramolecular cyclization to form the seven-membered azepane ring and a spontaneous intramolecular Michael addition to afford the five-membered furan ring. This synthetic route has also been demonstrated to be useful for the preparation of novel derivatives with simplified galanthamine skeletons.     

Model studies toward the total synthesis of the Lycopodium alkaloid spirolucidine

[reaction: see text] A strategy for the synthesis of the spirocyclic core of spirolucidine was explored through a model study. The diene 4a was prepared and photolyzed to give the desired [2 + 2] photoadduct 17 containing the correct relative stereochemistry corresponding to spirolucidine.     

Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization

The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.     

Dianion cyclization strategy for the synthesis of macrosilaheterocycles

A practical and efficient method for the preparation of silaheterocycles is described. The key step involves the initial formation of symmetrical chiral ditopic ligand, N,N′‐1,2‐cyclohexylenebis(salicylideneimine) followed by sequential deprotonation with NaH to form dianion intermediate, which reacts with diorganodichlorosilanes to furnish dibenzodioxadiazasilamacrocycles. The products were characterized by satisfactory elemental analyses and spectral (IR, ¹H, ¹³C, ²⁹Si NMR, and Mass) studies. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:455–460, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20460     

Asymmetric total synthesis of (-)-scabronine G via intramolecular double Michael reaction and Prins cyclization

The enantioselective total synthesis of (-)-scabronine G is described. The key features of the present synthesis include the construction of a 5-6 ring system containing two quaternary carbon centers via a diastereoselective intramolecular double Michael reaction and the formation of a seven-membered ring using a Prins cyclization.     

First asymmetric total syntheses of cernuane-type Lycopodium alkaloids, cernuine, and cermizine D

The first total syntheses of two cernuane-type Lycopodium alkaloids, (-)-cernuine and (+)-cermizine D, were accomplished starting from (+)-citronellal. The syntheses involved organocatalytic alpha-amination to afford oxazolidinone, which is used for diastereoselective allylation, and asymmetric transfer aminoallylation followed by stereoselective construction of an aminal moiety as key steps.     

Ten new Lycopodium alkaloids having the lycopodane skeleton isolated from Lycopodium serratum Thunb

Ten new alkaloids, lycoposerramines-F (1), -G (2), -H (3), -I (4), -J (5), -K (6), -L (7), -M (8), -N (9), and -O (10), having lycopodine-related structures, were isolated from the club moss Lycopodium serratum THUNB. and their structures were elucidated on the basis of spectroscopic analysis and/or chemical transformation.     

Flexible strategy for the synthesis of pyrrolizidine alkaloids

A general strategy for the production of pyrrolizidine alkaloids is described, starting from intermediate (+)-9. The key features are diastereoselective dihydroxylation, inversion at the ring junction by hydroboration of an enamine, and ring closure to form the bicyclo ring system. This route is attractive because of its brevity and versatility; four natural products were prepared with differing stereochemistry and substitution patterns. Finally, this work allowed assignment of the absolute stereochemistry of 2,3,7-triepiaustraline and hyacinthacine A 7.     

New strategy for the synthesis of tetrahydroisoquinoline alkaloids

[reaction: see text] A general strategy for the formation of 1,3-cis-substituted tetrahydroisoquinolines is described from ortho-iodo imines involving Larock isoquinoline synthesis, addition of organolithium compounds to unactivated isoquinolines, and ionic hydrogenation. In addition, a new synthesis of lactams via an unprecedented azide cyclization in the presence of a sulfonium ion is described.     

Toward a total synthesis of the stemofoline alkaloids: Advancement of a 1,3-dipolar cycloaddition strategy

Novel, intramolecular 1,3-dipolar cycloadditions of azomethine ylides have been applied to the synthesis of functionalized core structures of the stemofoline alkaloids. In an effort to maximize the efficiency of this key transformation in the context of an eventual total synthesis of these complex natural products, a number of strategic modifications to the cycloaddition substrate were investigated. The collective efforts have provided useful insights into the operative, regiochemical control elements for 1,3-dipolar cycloadditions leading to stemofoline alkaloids. A potential intermediate in the synthesis of these alkaloids was prepared.     

IMDA/retro-Mannich approach to cis-perhydroquinoline Lycopodium alkaloids: asymmetric synthesis of (+)-luciduline

[formula: see text] The first chiral auxiliary mediated asymmetric synthesis of the naturally occurring Lycopodium alkaloid (+)-luciduline has been accomplished. Key steps include an IMDA reaction of a chiral dihydropyridine, a subsequent retro-Mannich ring opening, and a novel cationic reductive cyclization reaction.     

Radical-initiated cyclization as a key step for the synthesis of oxoprotoberberine alkaloids

The oxoprotoberberine alkaloids 1a-d have been synthesized efficiently from the enamide derivatives 2a-d by a radical-initiated cyclization reaction utilizing n-Bu₃SnH/AIBN and CuCl. The enamide derivatives 2a-d were prepared from phenylethylamine analogues 5a-b, followed by acylation with acetic anhydride, Bischler-Napieralski cyclization with POCl₃ and benzoylation with the corresponding bromobenzoyl chloride, respectively.     

Enantioselective total synthesis of tricyclic myrmicarin alkaloids

[reaction: see text] An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations in this convergent approach include a stereospecific palladium-catalyzed N-vinylation of a pyrrole with a vinyl triflate, a copper-catalyzed enantioselective conjugate reduction of a beta-pyrrolyl enoate, and a regioselective Friedel-Crafts reaction. The synthesis of optically active and isomerically pure samples of (4aR)-myrmicarins 215A, 215B, and 217 in addition to their respective C4a-epimers is presented.     

Recent progress in Michael addition-based fluorescent probes for sulfur dioxide and its derivatives

In this review, we have summarized the recent progress of Michael addition-based fluorescent probes for SO₂ and its derivatives in the design strategies, sensing performances, detection mechanisms and applications.     

A novel total synthesis of elaeocarpus alkaloids

The novel synthesis of elaeocarpus alkaloids has been achieved employing 1,3-dipolar cycloaddition reaction as a key step.     

Unified strategy for the synthesis of the "miscellaneous" lycopodium alkaloids: total synthesis of (+/-)-lyconadin A

Total synthesis of the Lycopodium alkaloid lyconadin A was achieved in 18 steps starting from a readily available vinylogous ester and bromopicoline. The key step in the total synthesis is a proximity-driven oxidative C-N bond-forming reaction that yields the lyconadin pentacycle from a tetracyclic precursor. The key tetracycle, which has been prepared for the first time, is a versatile intermediate that may be utilized for the total synthesis of a variety of Lycopodium alkaloids. Critical to the success of this plan was the efficient preparation of a pyridine-annulated cycloheptadiene tricycle that promises to be a general strategy to access a variety of seven-membered ring containing natural products.     

Studies directed towards the total synthesis of morphine alkaloids

Application of metallated enamines to the synthesis of morphine related congeners is reported. A formal total synthesis of (±)-morphine has been completed.