Abstract The latrunculins are highly selective actin‐binding marine natural products and as such play an important role probe molecules for chemical biology. A short, concise largely catalysis‐based approach to this family of bioactive macrolides is presented. Specifically, the macrocyclic skeletons targets were forged by ring‐closing alkyne metathesis (RCAM) or enyne–yne suitable diyne precursors, respectively. This transformation was best achieved with aid [( t Bu)(Me 2 C 6 H 3 )N] Mo ( 37...

North and South: The unique biological activity of the natural product spirastrellolide A renders it an attractive lead for anticancer agents. southern hemisphere (C1–C25) northern (including chlorinated [5,6,6]-bis-spiroacetal entity lateral C42–C47 chain) are prepared by concise efficient routes. Consequently, entire carbon framework this potent phosphatase inhibitor, which contains 21 chiral centers, is in optically active form, important step toward structure determination total...

North and South: The unique biological activity of the natural product spirastrellolide A renders it an attractive lead for anticancer agents. southern hemisphere (C1–C25) northern (including chlorinated [5,6,6]-bis-spiroacetal entity lateral C42–C47 chain) are prepared by concise efficient routes. Consequently, entire carbon framework this potent phosphatase inhibitor, which contains 21 chiral centers, is in optically active form, important step toward structure determination total...

Abstract The outstanding ability of dirhodium α,α,α′,α′‐tetramethyl‐1,3‐benzenedipropanoate [Rh 2 (esp) ; esp=α,α,α′,α′‐tetramethyl‐1,3‐benzenedipropanoate] to catalyze the cyclopropanation a wide range alkenes with malonate‐derived carbenoids under mild reaction conditions is reported in this communication. experimental protocol remarkably simple, uses readily accessible and stable dimethyl diazomalonate very low catalyst loading. More importantly, alkene employed as limiting reagent.

Abstract Deliberate digression from the blueprint of total syntheses latrunculin A ( 1 ) and B 2 reported in accompanying paper allowed for preparation a focused library “latrunculin‐like” compounds, which all characteristic structural elements these macrolides were subject to pertinent molecular editing. Although previously derivatives essentially devoid any actin‐binding capacity, synthetic compounds presented herein remain fully functional. One designer molecules with relaxed macrocyclic...

Marvel of the sea: A concise and highly convergent total synthesis methyl ester marine macrolide spirastrellolide F (see picture), which has exquisite antimitotic properties, is reported. In this approach, northern southern hemispheres intricate target are stitched together in only two consecutive steps (Suzuki coupling, Yamaguchi lactonization) without any interim protecting-group manipulations.

Two largely catalysis-based and highly convergent total syntheses of latrunculin A ( 1 ) B 2 were diverted to the preparation a focused library analogues these potent actin-binding macrolides that enjoy widespread use in chemical biology. Because chosen route allows for structural variations all characteristic parts natural leads, it was possible map previously unknown structure/activity profile this class bioactive products. This led discovery removal methyl branches decorating macrocycle...

Different methods for the formation of C.25–C.26 bond spirastrellolide A (1) are evaluated that might qualify end game projected total synthesis, with emphasis on metathetic ways to forge macrocyclic frame.

Nord und Süd: Der marine Naturstoff Spirastrellolid A ist wegen seiner einzigartigen biologischen Aktivität eine attraktive Leitstruktur für neuartige Krebstherapeutika. Die südliche (C1–C25) die nördliche Hemisphäre (einschließlich der chlorierten [5,6,6]-Bis(spiroacetal)-Einheit lateralen Kette C42–C47) wurden auf einfache effiziente Art synthetisiert. Somit das gesamte Kohlenstoffgerüst dieses wirksamen Phosphatase-Inhibitors, 21 Chiralitätszentren enthält, in optisch aktiver Form...

[reaction: see text] Semipinacol-type rearrangements to produce azaspirocyclic ketones are presented. The yields and stereoselectivities of these reactions range from 67-94% yield 2.8:1 1:0 diastereoselectivity, respectively.

Azaspirocyclic ring systems are present in a variety of alkaloids. Functionalized 1-azaspirocyclopentanones (6, 7, 11, 12) can be efficiently constructed through semipinacol expansion reactions 2-(1-hydroxycyclobutyl)-p-toluenesulfonylenamides (4) promoted by either Bronsted acid ((S)-(+)-10-camphorsulfonic or HCl) N-bromosuccinimide, an electrophilic bromine source. Reactions N-bromosuccinimide tend to proceed higher yields (80-95%) and with greater diastereoselectivity (3:1-1:0) compared...

An asymmetric formal synthesis of fasicularin (1) is described. This natural product, isolated from the extracts marine invertebrate Nephteis fasicularis, has shown modest cytotoxicity towards Vero cells. Fasicularin among only two members cylindricine family products, along with lepadiformine (2), to possess a trans A-B ring junction. Key steps this approach 1 involve siloxy-epoxide semipinacol rearrangement 5 6, B-alkyl Suzuki-Miyaura coupling reaction by using enol...

[reaction: see text] Our synthetic approach toward fasicularin is presented. Key steps in this construction are a siloxy-epoxide semipinacol rearrangement, B-alkyl Suzuki reaction and an intramolecular S(N)2 reaction.

The construction of 1-azaspirocyclic cycloalkanones using a siloxy-epoxide semipinacol ring expansion process was examined. Functionalized 1-azaspiro[5.5]undecan-7-ones (1-azaspirocyclic cyclohexanones) proceeded in high chemical yields with complete diastereoselectivity titanium tetrachloride as the Lewis acid promoter. formation functionalized 6-azaspiro[5.4]-decan-1-ones cyclopentanones) yield little diastereoselectivity. Modification reaction parameters such promoter or nature silyl...

Peroxide bleaching is significantly affected by transition and alkaline earth metals. Isolating the effects of different metals on reactions peroxide with representative lignin structures allows separation positive from negative contributions these metal ions. In this work, five monomeric or dimeric phenolic model compounds were treated hydrogen in absence presence Mn 2+ , Cu Fe 3+ Mg . We followed disappearance starting material progress demethylation, radical coupling oxalic acid formation...

The final two steps used to prepare greater than 1 kg of a compound evaluated as treatment for type 2 diabetes are reported. application palladium-catalyzed C–O coupling presented significant challenges due the nature reactants, impurities produced, and noncrystalline intermediate. Process development was able address these limitations enable production kilogram quantities active pharmaceutical ingredient (API) in efficiency Mitsunobu reaction formation key bond. sequence that telescopes...

Wunder der See: Die kompakte und hoch konvergente Totalsynthese des Methylesters marinen Makrolids Spirastrellolid F (siehe Bild) wurde abgeschlossen. Dabei wurden die nördlichen südlichen „Hemisphären“ in nur zwei Stufen ohne zwischengeschaltete Schutzgruppenmanipulationen zusammengefügt (Suzuki-Kupplung, Yamaguchi-Lactonisierung).

This manuscript describes the development of a control strategy for impurities in final intermediate step asunaprevir drug substance utilizing concepts outlined International Conference on Harmonisation guidelines (ICH Q8 (R2), Q9, Q10, and Q11). Detailed mechanistic understanding enabled construction kinetic model that was used conjunction with process risk assessment well-defined quality attributes to guide reaction design space. Implementation continuous monitoring facilitated expansion...

Propylphosphonic anhydride has been shown to be an effective reagent for the synthesis of substituted [1,2,4]triazolo[1,5-a]pyridines from corresponding N′-hydroxy-N-formimidamides. The reactions worked under mild conditions and exhibited wide functional group tolerance, delivering triazolopyridines in good excellent yields purities.

ADVERTISEMENT RETURN TO ISSUEPREVAdditions & Corr...Additions CorrectionsNEXTA Formal Construction of FasicularinMichaël D. B. Fenster and Gregory R. DakeCite this: Org. Lett. 2004, 6, 7, 1187Publication Date (Web):February 14, 2004Publication History Published online14 February 2004Published inissue 1 April 2004https://pubs.acs.org/doi/10.1021/ol040012fhttps://doi.org/10.1021/ol040012fcorrectionACS PublicationsCopyright © 2004 American Chemical Society. This publication is available under...

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