Preparation of t-Acetylenic Chlorides<sup>1</sup>

Hennion, G. F.; Boisselle, Armand P.

doi:10.1021/jo01062a019

Cited by 64 publications

(26 citation statements)

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“…25,26) Chelation of the 11-hydroxy group of 6 by the carbonyl at the 12-position permitted the selective O-alkylation of the 9-hydroxy group with 3-chloro-3-methylbut-1-yne (9), 27) to give the corresponding propargylic ether 10. Methylation of the 11-hydroxy group of 10, carried out with dimethylsulfate in the presence of sodium hydride, gave 11.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Cytotoxic Activity of Benzo[a]pyrano[3,2-h] and [2,3-i]xanthone Analogues of Psorospermine, Acronycine, and Benzo[a]acronycine

Sittisombut¹,

Boutefnouchet²,

Van-Dufat³

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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Section: Chemistrymentioning

confidence: 99%

Synthesis and Cytotoxic Activity of Benzo[a]pyrano[3,2-h] and [2,3-i]xanthone Analogues of Psorospermine, Acronycine, and Benzo[a]acronycine

Sittisombut¹,

Boutefnouchet²,

Van-Dufat³

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…19) The starting 1,4,9-trimethyl-9H-carbazol-3-ol (20) was first conveniently prepared by hydrogen peroxide oxidation of the known 1,4,9-trimethyl-9H-carbazole-3-carbaldehyde (21). 15) Further treatment of 20 with 3-chloro-3-methylbut-1-yne 20) in the presence of sodium hydride in refluxing toluene afforded the desired 19 (Chart 2). Nevertheless, the difficulties encountered in both terms of yield and separation of isomers in the course of the preparation of 21 from 1,4,9-trimethylcarbazole severely limited the practical scope of syntheses using N-methycarbazoles as starting materials.…”

Section: Synthesis and Cytotoxic Activity Of Pyranocarbazole Analoguementioning

confidence: 99%

Synthesis and Cytotoxic Activity of Pyranocarbazole Analogues of Ellipticine and Acronycine

Tran-Thi¹,

Nguyen-Thi²,

Michel³

et al. 2004

CHEMICAL & PHARMACEUTICAL BULLETIN

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Natural products including a carbazole basic skeleton fused with another heterocyclic system currently receive a strong attention, due to the promising antitumor properties of several of their representatives.1) Of particular interest in this field are the pyrido [4,3-b]carbazole alkaloids and the indolo[2,3-a]carbazole antibiotics. The first series, illustrated by ellipticine (1) and 9-methoxyellipticine (2), both isolated from Ochrosia species (Apocynaceae) include compounds which act by intercalation within the DNA-double strand, followed by inhibition of topoisomerase II.2) A derivative of ellipticine, elliptinium (3), has been commercialized for the treatment of metastatic breast cancer.3) Rebeccamycine (4), isolated from Saccharothrix aerocolonigenes, is a typical representative of the second series currently under clinical trials. It induces topoisomerase I mediated DNA-cleavage. 4)The antitumor activity of several related indolocarbazoles has been recently discussed. 5)The structurally related pyrano[2,3-c]acridone alkaloid acronycine (5) isolated from Achronycia baueri SCHOTT. (Rutaceae) was shown to exhibit antitumor properties against a broad spectrum of solid tumor models.6-8) Nevertheless, its moderate potency and low water solubility rapidly appeared as severe drawbacks for a possible introduction into the clinic. A hypothesis of bioactivation of the 1,2-double bond of the chromene ring system of acronycine into the corresponding epoxide 9) led to the development of several series of more active structural analogues. The most significant improvements were obtained with diesters of 1,2-dihydroxy-1,2-dihydroacronycine 10) and, more recently, of 1,2-dihy-11) Representatives of this latter series, such as diacetate 6, are considered as valuable candidates for clinical studies.12) The mechanism of their action implies alkylation of the 2-amino group of DNA guanine residues by the ester leaving group at position 1 of the drug. 13,14) We describe here the synthesis and cytotoxic properties of various 2,2,5,11-tetramethyl-and 2,2,5,6,11-pentamethyl-2,6-dihydropyrano[3,2-b]carbazole derivatives. Such compounds associate the 1,4-dimethylcarbazole tricyclic system responsible for the intercalating properties of ellipticine related drugs, with the dimethylpyran pharmacophore of acronycine derivatives. ChemistryFor the synthesis of 2,2,5,11-tetramethyl-2,6-dihydropyrano[3,2-b]carbazole (7), the readily available 1,4-dimethyl-9H-carbazole-3-carbaldehyde (8), previously used as key-intermediate in several ellipticine syntheses, 15) was chosen as starting material. It was first oxidized by use hydrogen peroxide in acidic medium, into the corresponding 1,4-dimethyl-9H-carbazol-3-ol (9), according to the Matsumoto's procedure which has been applied by Langendoen et al. to the synthesis of related hydroxycarbazoles.16) Construction of the fused dimethylpyran ring was ensured by condensation of 9 Various 2,2,5,11-tetramethyl-and 2,2,5,6,11-pentamethyl-2,6-dihydropyrano[3,2-b]carbazole derivatives were synthesized by c...

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“…Some functionally substituted hexaalkenylbenzene derivatives containing oxygen or sulfur atoms in each of their six arms have also been prepared (16 to 24 % yield). The sixfold coupling of the less sterically encumbered 2,3,6,7,10,11-hexabromotriphenylene (24) gave the desired hexakis(3,3-dimethyl-1-butenyl)triphenylene (25) in 93 % yield. The first successful crosscoupling reaction of octabromonaphthalene (26) gave octakis-(3,3-dimethyl-1-butenyl)naphthalene (27) in 21% yield.…”

Section: Introductionmentioning

confidence: 99%

Six‐ and Eightfold Palladium‐Catalyzed Cross‐Coupling Reactions of Hexa‐ and Octabromoarenes

Stulgies

Prinz

Magull

et al. 2004

Chemistry A European J

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Palladium-catalyzed sixfold coupling of hexabromobenzene (20) with a variety of alkenylboronates and alkenylstannanes provided hexaalkenylbenzenes 1 in up to 73 % and 16 to 41 % yields, respectively. In some cases pentaalkenylbenzenes 21 were isolated as the main products (up to 75 %). Some functionally substituted hexaalkenylbenzene derivatives containing oxygen or sulfur atoms in each of their six arms have also been prepared (16 to 24 % yield). The sixfold coupling of the less sterically encumbered 2,3,6,7,10,11-hexabromotriphenylene (24) gave the desired hexakis(3,3-dimethyl-1-butenyl)triphenylene (25) in 93 % yield. The first successful cross-coupling reaction of octabromonaphthalene (26) gave octakis-(3,3-dimethyl-1-butenyl)naphthalene (27) in 21 % yield. Crystal structure analyses disclose that, depending on the nature of the substituents, the six arms are positioned either all on the same side of the central benzene ring as in 1 a and 1 i, making them nicely cup-shaped molecules, or alternatingly above and below the central plane as in 1 h and 23. In 27, the four arms at C-1,4,6,7 are down, while the others are up, or vice versa. Upon catalytic hydrogenation, 1 a yielded 89 % of hexakis(tert-butylethyl)benzene (23). Some efficient accesses to alkynes with sterically demanding substituents are also described. Elimination of phosphoric acid from the enol phosphate derived from the corresponding methyl ketones gave 1-ethynyladamantane (3 b, 62 % yield), 1-ethynyl-1-methylcyclohexane (3 c, 85 %) and 3,3-dimethylpentyne (3 e, 65 %). 1-(Trimethylsilyl)ethynylcyclopropane (7) was used to prepare 1-ethynyl-1-methylcyclopropane (3 d) (two steps, 64 % overall yield). The functionally substituted alkynes 3 f-h were synthesized in multistep sequences starting from the propargyl chloride 11, which was prepared in high yields from the dimethylpropargyl alcohol 10 (94 %). The alkenylstannanes 19 were prepared by hydrostannation of the corresponding alkynes in moderate to high yields (42-97 %), and the alkenylboronates 2 and 4 by hydroboration with catecholborane (27-96 % yield) or pinacolborane (26-69 % yield).

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Preparation of t-Acetylenic Chlorides¹

Cited by 64 publications

References 0 publications

Synthesis and Cytotoxic Activity of Benzo[a]pyrano[3,2-h] and [2,3-i]xanthone Analogues of Psorospermine, Acronycine, and Benzo[a]acronycine

Synthesis and Cytotoxic Activity of Benzo[a]pyrano[3,2-h] and [2,3-i]xanthone Analogues of Psorospermine, Acronycine, and Benzo[a]acronycine

Synthesis and Cytotoxic Activity of Pyranocarbazole Analogues of Ellipticine and Acronycine

Six‐ and Eightfold Palladium‐Catalyzed Cross‐Coupling Reactions of Hexa‐ and Octabromoarenes

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Preparation of t-Acetylenic Chlorides1

Cited by 64 publications

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Synthesis and Cytotoxic Activity of Benzo[a]pyrano[3,2-h] and [2,3-i]xanthone Analogues of Psorospermine, Acronycine, and Benzo[a]acronycine

Synthesis and Cytotoxic Activity of Benzo[a]pyrano[3,2-h] and [2,3-i]xanthone Analogues of Psorospermine, Acronycine, and Benzo[a]acronycine

Synthesis and Cytotoxic Activity of Pyranocarbazole Analogues of Ellipticine and Acronycine

Six‐ and Eightfold Palladium‐Catalyzed Cross‐Coupling Reactions of Hexa‐ and Octabromoarenes

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Preparation of t-Acetylenic Chlorides¹