A new asymmetric synthesis of (+)-12b-epidevinylantirhine

We report a new asymmetric synthesis of the indole alkaloid derivative (+)-12b-epidevinylantirhine through stereoselective cyclization of a tethered indole nucleus onto an N-acyliminium ion intermediate, generated from a readily available non-racemic bicyclic lactam building block, and subsequent template modification through a highly diastereoselective conjugate addition protocol. In addition, we present the first X-ray crystal structure of this indole target.     

A one-pot three-component reaction for the preparation of highly functionalized tryptamines

We have developed a general one-pot method to provide highly functionalized tryptamine derivatives, via a Fischer indole type pathway. In this article, we demonstrate optimal conditions for a one-pot indole synthesis, allowing for the synthesis of a broad scope of 2-methyl tryptamine derivatives and a precursor for the synthesis of the core structure of some akuammiline alkaloids. Additionally, further modification of the indole products is described.     

Synthesis of indole alkaloid analogues: novel domino stereoselective electrophile addition--cyclizations of tryptophan-derived alpha-amino nitriles

The synthesis of new indole alkaloid analogues, containing a 1,2,4,5,10b,10c-hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole skeleton, via highly stereoselective novel domino cyclative halogenation or prenylation reactions of tryptophan-derived alpha-amino nitriles, is described.     

Synthesis of the western half of the lolicines and lolitrems

[reaction: see text] The synthesis of the highly substituted indole portion of the complex tremorgenic natural products lolicine A and B is presented. The Diels-Alder reaction of a quinone monoimine enables the synthesis of an appropriately substituted indole. The key step in the synthesis is a tandem isopropenyl cuprate addition/aldol cyclocondensation which provides the necessary functionality for elaboration to the 2,2,5,5-tetramethyltetrahydrofuran.     

A concise asymmetric total synthesis of aspidophytine

An expedient asymmetric total synthesis of aspidophytine is reported. A highly convergent strategy involving the sequential annulation of vinyl iodide 5 with indole 6 exploits varying modes of indole reactivity to provide aspidophytine in 23% over six steps from 5.     

A new entry to polycyclic indole derivatives via intramolecular imino Diels-Alder reaction: observation of unexpected reaction

A new, efficient, and highly diastereoselective synthesis of polycyclic indole derivatives through intramolecular imino Diels-Alder reaction of aminoanthraquinone with N-prenylated indole-2-carboxaldehydes in the presence of 20 mol % of triphenylphosphonium perchlorate (TPPP) is reported with extremely high cis selectivity in good yield.     

A multicomponent synthetic strategy for two-carbon-tethered 1,3-oxathiole-indole pairs

An efficient methodology for the multicomponent synthesis of new and highly functionalized heterocycles containing 1,3-oxathiole and indole units which are connected through an sp(2)-C(2) bridge has been developed. This domino reaction enables successful assembly of three new sigma bonds including a C-S bond and a C-O bond in a one-pot operation. Features of this strategy include mild conditions, convenient one-pot operation, and high stereo- and regioselectivity.     

Total synthesis of tryprostatins A and B

Three distinct synthetic routes to the 2-prenyl tryptophan core skeleton of tryprostatins and their total syntheses are described. The strategies include a traditional gramine-mediated coupling reaction, Fürstner indole synthesis, and our radical-mediated indole synthesis from o-alkenylphenyl isocyanide. The establishment of reliable conditions for the radical-mediated construction of indoles via a low-temperature radical initiator V-70 (2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile)) led to the highly efficient syntheses of tryprostatins A and B.     

Indole‐Diterpene Synthetic Studies: Total Synthesis of (−)‐21‐Isopentenylpaxilline

An efficient, stereocontrolled total synthesis of the complex indole‐diterpene alkaloid (?)‐21‐isopentenylpaxilline ( 1 ) has been achieved. Key elements of the synthesis include the stereocontrolled construction of the advanced eastern hemisphere (?)‐ 68 , involving a highly efficient union of the eastern and western fragments (?)‐ 68 and 5 exploiting our 2‐substituted indole synthesis, application of the Negishi π cycloalkylation tactic as a new, potentially general protocol for the construction of ring C, and the fragmentation of a β,γ‐epoxy ketone to introduce the tertiary OH group at C(13) in the indole diterpene skeleton.     

A novel total synthesis of the bioactive poly-substituted carbazole alkaloid carbazomadurin A

A new total synthesis of the neuronal cell-protecting carbazole alkaloid carbazomadurin A is described. The key step was an allene-mediated electrocyclic reaction involving an indole [b]-bond for the construction of a highly substituted carbazole ring. The E-alkenyl side chain at the C1 position of carbazole was introduced between O-triflate and alkenyl pinacol borate using the Suzuki-Miyaura reaction. SEM groups were cleaved with TBAF and the formyl group was reduced to provide carbazomadurin A.     

Total synthesis of (-)-21-isopentenylpaxilline

[structure: see text] The total synthesis of (-)-21-isopentenylpaxilline (1) has been achieved. Key elements of the synthesis include the stereocontrolled construction of the advanced eastern hemisphere (-)-5, a highly efficient union of the eastern and western fragments (-)-5 and 4, respectively, exploiting our 2-substituted indole synthesis, and a new protocol for the construction of ring C.     

A general synthesis of substituted indoles from cyclic enol ethers and enol lactones

[reaction: see text] X = CH2, C[double bond]O, R2 = H, alkyl. A general method was developed for the one-pot synthesis of highly functionalized indoles from simple, commercially available aryl hydrazines and cyclic enol ethers. Enol lactones were also used as substrates, affording substituted indole acetic acid or indole propionic acid derivatives. This procedure affords 2,3-disubstituted indoles as single regioisomers from the appropriately substituted enol ether or enol lactone. This method was highlighted in the efficient synthesis of the antimigraine drug sumitriptan and the antiinflammatory drug indomethacin.     

[3+2] Cycloaddition of metal-containing azomethine ylides for highly efficient synthesis of mitosene skeleton

Efficient synthesis of tricyclic indole derivatives bearing a substituent at the 3-position of the indole nucleus was achieved by the [3+2] cycloaddition reaction of transition metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines with vinyl ethers. Third-row transition metal complexes, especially PtCl₂, turned out to be highly efficient for the reaction of internal alkynes and imidate substrates with wide generality. Moreover, as strong support for the reaction mechanism, the intermediate Pt-carbene complex was found to undergo intramolecular C-H bond insertion reaction to give tetracyclic indoline derivatives when benzyl vinyl ether was employed as a dipolarophile. This protocol provided a facile synthesis of highly functionalized tricyclic indole derivatives found as the basic skeleton of the mitosene family, such as mitomycin C.     

A Divergent Polyene Cyclization for the Total Synthesis of Greenwayodendrines,Greenwaylactams, Polysin and Polyveoline

We present a concise asymmetric total synthesis (5–8 steps) of nine sesquiterpenoid alkaloids featuring four different tetra-/pentacyclic scaffolds. To this end, a novel, bioinspired indole N-terminated cationic tricyclization has been developed, enabling the divergent synthesis of greenwayodendrines and polysin. Subtle variation of the C2-substituted indole cyclization precursor allowed switching between indole N- and C-termination. For the latter, a subsequent Witkop oxidation enabled conversion of the cyclopentene-fused indole into the eight-membered benzolactam to directly furnish the family of greenwaylactams. In addition, a diastereomeric C-termination product has been elaborated to provide access to polyveoline.     

Catalyst free sequential one‐pot reaction for the synthesis of 3‐indole propanoates/propanoic acid/propanamides as antituberculosis agents

A highly efficient catalyst free one pot four component synthesis of highly functionalized three‐substituted indole derivatives has been reported. Thus, sequential catalyst free condensation of readily available aldehydes with Meldrum's acid followed by Michael addition of indole resulting three carbon component condensed product and concurrent decarboxylation by the nucleophilic attack of ethanol/water/amines affords three‐indole propanoates/propanoic acid/propanamides in affordable yields. Further, synthesized compounds and standard drugs were evaluated against Mycobacterium tuberculosis H37Rv strain by Alamar blue assay method. Majority of the compounds exhibited the superior activity and specifically compound 4d has MIC 1.6 μg/ml, which is better than the reference drugs used.     

Iridium‐Catalyzed Enantioselective Indole Cyclization: Application to the Total Synthesis and Absolute Stereochemical Assignment of (−)‐Aspidophylline A

The first enantioselective total synthesis of (?)‐aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. This strategy relies on the direct use of 2,3‐disubstituted indoles with secondary allylic alcohols appended at C2 and heteronucleophiles appended at C3, indoles which are easily prepared from simple starting materials under C?H activation conditions.     

Fluorinated N-[2-(haloalkyl)phenyl]imidoyl chloride, a key intermediate for the synthesis of 2-fluoroalkyl substituted indole derivatives via Grignard cyclization process

Fluorinated N-[2-(haloalkyl)phenyl]imidoyl chloride, which was readily available from the corresponding anilines by using Uneyama's one-pot synthesis of fluorinated imidoyl chloride, was found to be a key intermediate for the facile synthesis of 2-fluoroalkyl substituted indole derivatives via the Grignard cyclization process. The bromination of 3-methyl group of 3-methyl-2-trifluoromethyl indole with NBS/CCl₄ led to the formation of 3-bromomethyl substituted indole which can be further utilized to synthesize some new and biologically interested indole derivatives.     

Indole-tolerant Oxidation of 1,2-Diarylalkynes to 1,2-Diketone Derivatives

A new indole-tolerant oxidation condition for the synthesis of 1,2-diketone derivatives from the corresponding 1,2-diarylalkynes was described. By screening a series of oxidation systems on alkynes linked with indole and different substituted aromatic ring, the DMSO/PdCl₂/CuCl₂ system afforded moderate to good yields despite the existence of electron-rich indole ring.     

A diastereoselective total synthesis of trans-trikentrin A: a ring contraction approach

A new route to obtain the polyalkylated indole (+/-)-trans-trikentrin A was developed. The synthesis of this natural alkaloid features a thallium(III)-mediated ring contraction reaction to obtain the trans-1,3-disubstituted five-membered ring in a diastereoselective manner. Thallium(III) is chemoselective in this rearrangement, reacting with the olefin without oxidation of the indole moiety. Other key transformations are the Bartoli's reaction to construct the heterocyclic ring and a Heck coupling to add the carbons atom that will originate the nonaromatic cycle.     

Total Synthesis of (+)‐Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization

A new method for one‐step construction of the tetracyclic core structure of the indole alkaloid (+)‐minfiensine was developed utilizing a palladium‐catalyzed asymmetric indole dearomatization/iminium cyclization cascade. An efficient total synthesis of (+)‐minfiensine was realized using this strategy. The present method enables access to the common core structure of a series of monoterpene indole alkaloids, such as vincorine, echitamine, and aspidosphylline A.