A rapid, mild procedure for the preparation of alkyl chlorides and bromides

The development of resistance to endocrine therapy as well as chemotherapy is presently a major problem in the treatment of breast cancer. To minimize this obstacle, new, more selective and potent, chemotherapeutic agents should be designed. One way to improve selectivity is to link a cytotoxic moiety to a molecule possessing an affinity to the estrogen receptor (ER). The latter would be used to direct the cytotoxic portion of the molecule towards the target cells. Our initial approach led us to the synthesis of new triphenylethylene–platinum(II) complexes 1a–c. The commercially available desoxyanisoin (10) was efficiently transformed in seven steps into the platinum(II) complexes 1a–c with an overall yield exceeding 30%. The biological activity of compounds 1a–c was evaluated in vitro on ER+ and ER− human breast tumor cell lines: MCF-7 and MDA-MD-231.

Section: Introductionmentioning

confidence: 99%

Synthesis and preliminary in vitro biological activity of non-steroidal cytotoxic estrogens designed for the treatment of breast cancer

Bérubé¹,

Wheeler²,

Ford³

et al. 1993

“…22 3-Heptyn-1-01 was isomerized to the terminal alkyne in 90% yield as described for 9, which was then protected as the (2-methoxyethoxy)methyl ether in 81% yield (15). Compound 21 gave 'H nmr and mass spectra identical to that prepared previously (9).…”

Section: Preparation Of 10-undecyn-1-01 16mentioning

confidence: 91%

Improved syntheses of hydroxy acid precursors of macrolide pheromones of cucujid grain beetles

Oehlschlager¹,

Czyzewska²,

Aksela³

et al. 1986

Can. J. Chem. 64,1407 (1986. Syntheses of 11-and 12-hydroxy-(2)-3-dodecenic, 11-and 12-hydroxy-(Z,Z)-3,6-dodecadienic, and 13-hydroxy-(Z,Z)-5,8-tetradecadienic acids are reported. These unsaturated hydroxy acids are precursors of male-produced macrolide aggregation pheromones of grain beetles of the genera Cryptolestes and Oryzaephilus. The sequence of reactions for synthesis of the hydroxy-(Z)-3 acids was carboxylation of the dilithium salt of 10-or 11-hydroxy undecyne, deconjugation of the resulting carboxylic acids with NaNHz in THFIliquid ammonia to a mixture of 2,3-allenic and 3-alkynoic acids, and hydrogenation of the mixture with P-2 nickel catalyst. This latter reaction gave only the desired hydroxy-(Z)-3-alkenoic acids. The convergent point in the syntheses of the diunsaturated hydroxy-(Z,Z) acids was the coupling of the dimagnesium salt of 3-butyn-1-01 or 5-hexyn-1-01 to the appropriate functionalized propargylic bromide. The resulting 1 ,Cdiacetylenic alcohols were oxidized with Jones reagent to the corresponding carboxylic acids, which were hydrogenated over P-2 nickel catalyst and deprotected. convergence des synthbses des hydroxy-acides di'insaturks-(Z,Z) est le couplage du sel de dimagnksium du butyne-3 01 ou de I'hexyne-5 01 avec le bromure propargylique fonctionnalisk d'une f a~o n appropriie. On a oxydt les alcools di-acktylkniques-l,4 qui en rksultent avec le rtactif de Jones; on a hydrogknt les acides carboxyliques correspondants sur un catalyseur P-2 de nickel et on les a ensuite dkprotkgt.[Traduit par la revue] Introduction During the past several years, we have reported (1-6) the discovery of seven macrolide aggregation pheromones for five species of grain beetles (Table 1). These well-known cucujids are economically-important pests during grain storage, food processing and distribution, and in households. The beetles infest a wide variety of stored-product commodities such as grain, cereal-based foods, nuts, chocolate, oil seeds and cake, raisins and other dried fruits, and spices.Our initial syntheses (7-9) of these macrolides were long and, in cases, inefficient, but furnished sufficient amounts of the pheromones for laboratory bioassays. In order to supply selected macrolides for laboratory trap tests and limited field trials, we have devised more efficient syntheses of the o and o -1 hydroxy acid precursors of macrolides 1-4 and 6. As in previous approaches, we have utilized functionalized alkynes for carbon-carbon bond formation by coupling with appropriate electrophiles and for conversion into the required Z-olefinic bonds. In this paper, we report new syntheses for the hydroxy acid precursors of macrolides 1 and 6 and improved routes to those of macrolides 2-4.

“…The cleavage of the silyl ether protecting group of trienes 236 and 23c was effected with n-Bu,NF in good yields (18). The resulting allylic alcohol 24b was then transformed into the corresponding allylic chloride 250 by Meyers' procedure (14), while the allylic alcohol 24c was converted to the allylic bromide 25c using carbon tetrabromide and triphenylphosphine in dichloromethane (20). A slight decomposition was observed when allylic halides 256 and 25c were submitted to purification by flash chromatography.…”

Section: Preparations Of Macroc~~clesmentioning

confidence: 99%

Stereocontrolled construction of 1,7-dimethyl A.B.C.[6.6.6] tricycles. Part I. Transannular Diels–Alder reactions of 14-membered macrocycles containing trans-dienophiles

Xu¹,

Roughton²,

Plante³

et al. 1993

. Transannular Diels-Alder reactions of 14-membered macrocyclic trienes possessing a methyl substituent on both the diene and dienophile moiety have been investigated. Macrocyclic structures l a , l b , and l c having cis-trans-trans (CTT), trans-cis-trans (TCT), and trans-trans-trans (TTT) geometries could be stereoselectively constructed by coupling appropriately functionalized dienes 5 and dienophile 4 following an intramolecular displacement of an allylic halide by the anion of an appropriately located dimethyl malonate unit. The transannular Diels-Alder reaction performed on l a led to a mixture of four major tricyclic products, including 34 possessing the unexpected trans-anti-cis (TAC) stereochemistry. When heated at 300°C, macrocycle 10 underwent an unique conversion via an ene-retroene, Diels-Alder process, producing the unexpected tricycle 41 (racemic form) containing five contiguous chiral centers. A rationale for the above experimental facts is presented. In contrast to the previous results, the transannular Diels-Alder reaction of macrocycle l c was straightforward, producing a 95% isolated yield of trans-anti-cis (TAC) tricycle 34. This investigation demonstrates a general methodology for the stereocontrolled synthesis of 1,2-dimethyl A.B.C[6.6.6] tricyclic compounds, which are potential precursors to polycyclic natural products such as steroids and terpenes. YAO-CHANG XU, ANDREW L. ROUGHTON, RAYMOND PLANTE, SOLO GOLDSTEIN et PIERRE DESLONGCHAMPS. Can. J. Chem. 7 1 , 1152 (1993). La reaction de Diels-Alder transannulaire macrocycles a 14 chainons contenant un dikne et un diknophile substitues par un radical methyl est dCcrite. Les macrocycles l a , l b et l c de gComCtrie cis-trans-trans (CTT), trans-cis-trans (TCT), et trans-trans-trans (TTT)ont Ct C prepares de manikre stCreoselective par le couplage des dienes 5 et du diknophile 4 suivi par un deplacement intramolCculaire d'un halogenure allylique par l'anion d'une unite malonate. Le macrocycle l a fournit par une reaction de Diels-Alder transannulaire un melange de quatre produits tricycliques dont 34, produit inattendu, de stkreochimie trans-anti-cis (TAC). Par chauffage a 300°C le macrocycle l b subit une transformation unique par une suite de reactions kne-retrobne, Diels-Alder conduisant au tricycle inattendu 41 (forme rackmique) qui posskde cinq centres chiraux contigus. Une rationalisation de ces iaits experimentaux est proposke. Contrairement aux resultats precedents, la reaction Diels-Alder transannulaire effectuee sur le macrocycle l c donna comme attendu le tricycle transanti-cis (TAC) 34 avec un rendement de 95% en produit isole. Dks lors cette etude demontre une mtthodologie gCnCrale permettant de synthetiser de manikre stCreocontr6lCe des structures tricycliques 1.2-dimethyl A.B.C.[6.6.6], prkcurseurs potentiels de produits naturels tels les steroi'des et les terpknes.