A new synthetic approach to the C-D ring portion of streptonigrin analogues

Development of an efficient synthesis of the C-D ring portion of streptonigrin is a key operation in the synthesis of this antibiotic and its analogues. A new method for the synthesis of 3-cyano-5,6-dimethyl-4-(3,4,5-trimethoxyphenyl)-2-pyridone ( 14 ), a compound having the requisite functionality for conversion into a streptonigrin analogue, has been established. It involves treatment of 3,4,5-trimethoxybenzonitrile with ethylmagnesium bromide and malononitrile to give propylenemalononitrile derivative 7 , which is condensed with trimethyl orthoacetate to give a mixture of 9 and pyridine derivative 12 . Demethylation of 12 then affords 14 . The overall yield for this route was 50%, allowing for conversion of 9 to 12 .     

7-Substituted prostaglandin analogues. A new synthetic approach

Starting from methyl 7-oxo-7-(1-cyclopentene)-heptanoate, a simple synthesis of the methyl esters of 7-oxo- and 7-hydroxy-9,11-dideoxy-PGF ₁ as a model for 7-substituted prostaglandin analogues is described.

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7-Substituierte Prostaglandin-Analoge — ein neuer Syntheseweg

Zusammenfassung Ausgehend von Methyl-7-oxo-7-(1-cyclopenten)-heptanoat wird eine einfache Synthese der Methylester von 7-Oxo- und 7-Hydroxy-9,11-dideoxy-PGF ₁ als Modellverbindungen für 7-substituierte Prostaglandinanaloge beschrieben.

     

A new synthetic approach to the C ring of known as well as novel bryostatin analogues

[reaction: see text] A new approach to the synthesis of the C ring subunit of known and potential bryostatin analogues is described. The convergent approach, illustrated above, requires fewer steps and offers greater flexibility in rapidly accessing diverse C ring analogues.     

Total synthesis of macrosphelide A by way of palladium-catalyzed carbonylative esterification

We achieved the total synthesis of macrosphelide A, as part of a combinatorial library of its analogues. The key intermediate, the seco-acid derivative, was prepared from the corresponding vinyl iodide using sequential carbonylative esterification.     

A new synthetic entry to the tricyclic skeleton of FR901483 by palladium-catalyzed cyclization of vinyl bromides with ketone enolates

A new synthetic entry to the FR901483 core is described. The Pd-mediated cyclization of amino-tethered vinyl halides and ketone enolates from the azaspiro[4.5]decan-8-ones 5 and 10 gives the functionalized 7,10a-methanoperhydropyrrolo[1,2-a]azocines 1 and 11, respectively.     

A synthetic approach to bicyclo[6.2.1]undecane ring systems

A synthesis of a functionalized bicyclo[6.2.1]undecane, N-(7-hydroxymethyl-bicyclo[6.2.1]undeca-3,5,9-trien-2-yl)-4-methyl-benzenesulfonamide, is described. Starting with a [6+4] cycloaddition between cyclopentadiene and cycloheptatrienone, the final product was prepared in five steps with an overall 37% yield. The remarkable resistance to hydrolysis of an intermediate lactam was overcome by tosylating the amide and reducing with LiAlH₄.     

The shortest synthetic route to puromycin analogues using a modified Robins approach

We are reporting on the utility of commercial vinyl isocyanate for a practical synthetic route from adenosine to N(6)-bis-demethylpuromycin in seven steps and 65% overall yield. A clean one-pot conversion of 3'-bromo-2'-carbamoyl derivative 8 to 3'-amino-3'-deoxyadenosine derivative 10 is the main feature of this synthetic pathway. This synthesis is the shortest synthetic route toward 3'-(aminoacylamido)deoxyadenosines to date.     

A synthetic approach toward taxol analogs: studies on the construction of the CD ring

Tricycle 6, containing the CD ring of taxol, is constructed from (S)-(+)-carvone in 21 steps involving a Diels-Alder reaction with isoprene, a Baeyer-Villiger oxidation, an Oppenaurer oxidation and Meerwein-Ponndorf-Verley reduction, a stereospecific Grignard addition, and an intramolecular S_N2 reaction as the key steps.     

A recyclable palladium-catalyzed modified Friedländer quinoline synthesis

2-Aminobenzyl alcohol reacts with an array of ketones in toluene/poly(ethylene glycol) (PEG-2000) at 100 °C in the presence of a palladium catalyst along with KOH under an atmosphere of air to give the corresponding quinolines in good yields. The catalytic system could be recovered and reused five times without any loss of catalytic activity.     

A new route to phenylenedimalononitrile and the analogues using palladium-catalyzed carbon-carbon bond formation

Phenylenedimalononitrile and the analogues, which are key intermediates in the synthesis of TCNQ and the analogues, are prepared directly by the Pd-catalyzed reaction of-diiodoarenes with malononitrile anion.     

A new synthetic approach to the bicyclo[5.3.1]undecane ring system in taxanes

The bicyclo[5.3.1]undecane derivative 19, which was referred to the A,b ring system of taxane diterpenes, was synthesized by a base-induced fragmentation reaction of the tricyclic diol monomesylate 18 derived highly stereoselectively from 5-methyl-1,3-cyclohexadione.     

A Palladium‐Catalyzed Carbonylation Approach to Eight‐Membered Lactam Derivatives with Antitumor Activity

The reactivity of 2‐(2‐alkynylphenoxy)anilines under PdI₂/KI‐catalyzed oxidative carbonylation conditions has been studied. Although a different reaction pathway could have been operating, N‐palladation followed by CO insertion was the favored pathway with all substrates tested, including those containing an internal or terminal triple bond. This led to the formation of a carbamoylpalladium species, the fate of which, as predicted by theoretical calculations, strongly depended on the nature of the substituent on the triple bond. In particular, 8‐endo‐dig cyclization preferentially occurred when the triple bond was terminal, leading to the formation of carbonylated ζ‐lactam derivatives, the structures of which have been confirmed by XRD analysis. These novel medium‐sized heterocyclic compounds showed antitumor activity against both estrogen receptor‐positive (MCF‐7) and triple negative (MDA‐MB‐231) breast cancer cell lines. In particular, ζ‐lactam 3 j′ may represent a novel and promising antitumor agent because biological tests clearly demonstrate that this compound significantly reduces cell viability and motility in both MCF‐7 and MDA‐MB‐231 breast cancer cell lines, without affecting normal breast epithelial cell viability.     

A new synthetic approach to phosphatidylethanolamine

A new synthetic method for phosphatidylethanolamine head group was developed via ring-opening of cyclic dioxaphospholane 2 with sodium azide and subsequent hydrogenation.The advantage of this strategy included short reaction steps,readily available materials and good yields.     

A new synthetic approach to benzomorphans

A new approach to the synthesis of benzomorphan derivatives is exemplified by the obtention of 3,6-dimethyl-benzomorphan from the readily available 1-methyl-2,3-benzobicyclo-[3,2,l]octane-4,6-dione.