Total synthesis of (+)-frondosin A. Application of the Ru-catalyzed [5+2] cycloaddition

The first total synthesis of (+)-frondosin A was accomplished in 19 longest linear and 21 total steps from commercially available materials. The key features of the synthesis include a Ru-catalyzed [5+2] cycloaddition, a Claisen rearrangement, and a ring expansion to construct the core of the frondosin A in a diastereoselective and regioselective fashion. This is the first application of a Ru-catalyzed [5+2] cycloaddition in the total synthesis of a natural product. Through this synthesis, the absolute configuration of (+)-frondosin A was established.     

Regioselective preparation of 2-substituted 3,4-diaryl pyrroles: a concise total synthesis of ningalin B

Methylisocyanoacetate undergoes a 2 + 3 cycloaddition with alpha,beta-unsaturated nitriles to provide a regioselective synthesis of 2-substituted 3,4-diaryl pyrroles. The ease of preparation of alpha,beta-unsaturated nitriles allows the rapid synthesis of pyrroles with varied substituents. Using this method, a key intermediate (1) for the synthesis of the marine natural products lukianol A, lamellarin O, and lamellarin Q was prepared in two steps. A total synthesis of ningalin B (11) was also accomplished utilizing this methodology.     

Efficient total syntheses of phytoalexin and (+/-)-paniculidine B and C based on the novel methodology for the preparation of 1-methoxyindoles

A general route to 2-unsubstituted-1-methoxyindoles, based on our methodology for the synthesis of 1-methoxyindoles, is reported. This synthesis renders accessibility to a variety of natural products possessing the said skeleton. A direct synthesis of phytoalexin (1), (+/-)-paniculidine B (2), and (+/-)-paniculidine C (3) is disclosed based on the methodology. The synthesis of paniculidine B (2) has been achieved from aldehyde 10 in only two steps in 88% yield and in five steps from a methoxyindole compound 8 obtained using our earlier methodology.     

A metalation strategy for the construction of functionalized naphthalenes: the first synthesis of guieranone A

The first synthesis of the natural product guieranone A is described, demonstrating a one-pot procedure for the synthesis of protected-1,3,6,8-tetraoxygenated naphthalenes and a subsequent directed metalation synthesis of 2-keto naphthalenes.     

Synthesis of a new trans-A2B2 phthalocyanine motif as a building block for rodlike phthalocyanine polymers

Polyphthalocyanines have potential application in the development of electronic materials. One-dimensional polyphthalocyanines are accessible through monomers having a trans-A2B2 structure, but the preparation of a truly linear polyphthalocyanine is challenging because of limitations imposed by the geometry of phthalocyanines and the methodology for their synthesis. Benzimidazoporphyrazines are a known class of extra-annulated phthalocyanines. A trans-A2B2 benzimidazoporphyrazine is geometrically suitable for the preparation of rodlike polymers. A new synthesis of benzimidazoporphyrazines is presented as a stepping stone to the synthesis of trans-A2B2 benzimidazoporphyrazines.     

Total synthesis of callipeltoside A

A convergent total synthesis of cytotoxic marine macrolide callipeltoside A is described. The synthesis highlights two stereoselective [4 + 2] annulations for the preparation of associated pyran rings.     

Synthesis of adenylyl-(3'----5')-guanosine and some analogues as probes to explore the molecular mechanism of stimulation of influenza virus RNA polymerase

Influenza virus mRNA synthesis is primed by a capped oligonucleotide which is cleaved off from a cellular mRNA by a viral protein. The dinucleotide A3'p5'G can be used as a primer for the viral RNA polymerase mediated RNA synthesis in a cell-free system. Analogues of A3'p5'G have therefore been synthesized using the phosphotriester approach, and their priming ability for the influenza virus mRNA synthesis has been determined. An absence of the 2'-hydroxyl function in the guanosine residue in the dinucleotide, as in A3'p5'dG, drastically decreased its priming ability. Similarly, an alteration of the 3'----5' phosphate linkage to a 2'----5' phosphodiester linkage affected the priming ability quite severely. However a dinucleotide, with the 2'-hydroxyl function omitted in the adenosine moiety, as in dA3'p5'G, could still stimulate the mRNA synthesis. None of the modified dinucleotides inhibited A3'p5'G or globin mRNA primed influenza mRNA synthesis.     

A new approach to construct full-length glycosylphosphatidylinositols of parasitic protozoa and [4-deoxy-Man-III]-GPI analogues

A new [2 + 2 + 2] approach to construct GPI molecules through the efficient synthesis of glucosamine-inositol and tetramannose intermediates led to a total synthesis of a GPI-anchor of Trypanosoma cruzi, and also afforded a key intermediate for the synthesis of valuable [4-deoxy-Man-III]-GPI analogues.     

Total Synthesis of Antitumor Antibiotic Derhodinosylurdamycin A

The first total synthesis of derhodinosylurdamycin A, an angucycline antitumor antibiotic, has been described. The synthesis features a Hauser annulation followed by pinacol coupling to construct the tetracyclic angular aglycon, a Stille coupling of glycal stannane and tetracyclic aryliodide followed by stereoselective reduction to afford the 2‐deoxy β‐C‐arylglycoside, and a late‐stage stereoselective glycosylation for the preparation of derhodinosylurdamycin A. This synthetic strategy should be amenable to the chemical synthesis of analogs of derhodinosylurdamycin A bearing diverse 2‐deoxy sugar subunits for structure and activity relationship studies.     

CoIIIcorrole: versatile synthetic methods and wide range of applications

Journal of Inclusion Phenomena and Macrocyclic Chemistry - This review introduces the synthesis, properties and applications of CoIIIcorroles. The synthesis methods are containing A2B type, A3...     

Synthesis of 2-amino-3-methoxypyrazinc

A new synthesis of 2-amiuo-3-methoxypyrazine, an intermediate in the synthesis of sulfalene, via 2-carbamido-3-hydroxy pyrazine and subsequent Hofmann rearrangement of 2-carhamido-3-methoxypyrazine, is described.     

Synthesis of maremycins A and D1 via cycloaddition of a nitrone with (E)-3-ethylidene-1-methylindolin-2-one

A concise synthesis of maremycins A and D1 has been accomplished via cycloaddition of a chiral cyclic nitrone with ( E)-3-ethylidene-1-methylindolin-2-one as a key step. This synthesis clarifies the stereochemistry of the maremycins and is suitable for large-scale synthesis for biological screening.     

New synthesis of optically active 5-isoxazolidinones and beta-amino acids

A new simple and stereoselective synthesis of 5-isoxazolidinones based on the reaction of lithiated 2-isopropyl-2-oxazolines with nitrones is described. A chiral version of such a methodology allows the preparation of highly enantioenriched 5-isoxazolidinones which are useful precursors for the synthesis of beta-amino acids     

Regiocontrolled synthesis of pyrrole-2-carboxaldehydes and 3-pyrrolin-2-ones from pyrrole Weinreb amides

A regiocontrolled synthesis of 3,4-disubstituted pyrrole-2-carboxaldehydes was completed in two steps from acyclic starting materials. A Barton-Zard pyrrole synthesis between N-methoxy-N-methyl-2-isocyanoacetamide and alpha-nitroalkenes or beta-nitroacetates provided N-methoxy-N-methyl pyrrole-2-carboxamides (pyrrole Weinreb amides), which were converted into the corresponding pyrrole-2-carboxaldehydes by treatment with lithium aluminum hydride. A regioselective oxidation of the pyrrole-2-carboxaldehydes gave the corresponding 3,4-disubstituted 3-pyrrolin-2-ones.     

An efficient palladium catalyzed synthesis of 2-arylbenzothiazoles

A novel and convergent palladium catalyzed synthesis of 2-arylbenzothiazoles has been investigated. The key step in the synthesis is a Suzuki biaryl coupling of 2-bromobenzothiazole with aryl boronic acids to provide a variety of 2-arylbenzothiazole derivatives in good yield. The synthetic utility of this methodology is demonstrated by the synthesis of 2-(4-aminophenyl)-6-methoxybenzothiazole, a PET probe precursor for the in vivo imaging of Alzheimer's disease.     

A Practical Formal Synthesis of a Physiologically Active Analogue of Platelet Activating Factor

A synthesis of phosphocholine 9 was accomplished in 36% yield from isopropylidene glycerol in contrast to 2% yield as reported previously. Since 9 has been converted to platelet activating factor-analogue 2, this report constitutes a more practical synthesis of 2.     

Practical syntheses of a CXCR3 antagonist

Two new, reliable syntheses of a pyrido[2,3-d]-pyrimidine inhibitor of the CXCR3 receptor are described. A nine-step synthesis of the CXCR3 inhibitor (1) from 2-aminonicotinic acid was demonstrated on a multikilogram scale and incorporates a classic resolution to deliver the enantioenriched active pharmaceutical ingredient (API). A second synthesis of the CXCR3 inhibitor starts from (+)-(D)-Boc alanine and 2-chloronicotinic acid and utilizes a Goldberg coupling. This second synthesis, performed on a gram scale, intersects the former route at a common intermediate thereby completing a formal synthesis of the enantioenriched API in higher overall yield without the need for a resolution.     

A Chiron-based Approach for the Synthesis of Tricyclic Tyrosine Analogue

A chiron approach-based enantioselective synthesis of designed tricyclic tyrosine analogue D-2 was developed. A SmI2-mediated free radical cyclization, an intramolecular Friedel-Crafts reaction and an intramolecular Mannich reaction served as key steps. These key steps were optimized and repeated in good yields. All the stereochemistries in the synthesis were established and confirmed.     

Total synthesis of d,1-occidentalol by photoannelation

A nine step synthesis of an intermediate previously used in the synthesis of the sesquiterpene occidentalol is reported which incorporates a 2+2 photocycloaddition reaction as the key carbon carbon bond forming step.     

Derivatives of sym-Triazine. 3. Synthesis and Some Conversions of Monoazides of the Triazine Series

A convenient preparative route has been developed for the synthesis of 2-azido-4-R-6-R'-sym-triazines, which are promising synthons in organic synthesis. A series of 2-(1-triazolyl)-sym-triazine derivatives has been synthesized for the first time from the obtained azides and acetylacetone or acetoacetic ester.