Tamoxifen, synthesis

Table sugar, sec Sucrose Tagatose, structure of, 975 Talose. configuration of, 982 Tamiflu, molecular model of, 130 Tamoxifen, synthesis of, 744 Till] DNA polymerase, PCR and, 1117 Tartaric acid, stereoisomers of, 305-306... 

A. Martinez, R. Olmo, I. Iglesias, J.M. Teijon, M.D. Blanco, Folate-targeted nanoparticles based on albumin and albumin/alginate mixtiu-es as controlled release systems of tamoxifen Synthesis and in vitro characterization, Pfiarmacewt. Res., 31,182-193,2014. 

Another example is tamoxifen (89). Its synthesis begins with Grignard addition of reagent to aryl ketone giving carbinol Dehydration leads to the readily separable and... 

The utility of the stepwise, double-coupling procedure is demonstrated in the parallel synthesis of Tamoxifen derivatives on solid support [127] (Scheme 1-29). 1-Alkenylboronates thus obtained by a diboration-cross coupling sequence are further coupled with p-silyUodobenzene supported on polymer resin. Using this strategy, each position about the ethylene core is modified by the appropriate choice of alkyne, aryl halide, and cleavage conditions for the synthesis of a library of Tamoxifen derivatives. 

Several Grignard reactions are used on an industrial scale in drug synthesis.95 The syntheses of both tamoxifen and droloxifene, which are estrogen antagonists used in treatment of breast cancer and osteoporosis, respectively, involve Grignard addition... 

Mixed anhydrides with trifluoroacetic acid are particularly reactive acylating agents.48 For example, Entry 5 in Scheme 11.4 shows the use of a mixed anhydride in the course of synthesis of the anticancer agent tamoxifen. 

Scheme 11.4 shows some other representative Friedel-Crafts acylation reactions. Entries 1 and 2 show typical Friedel-Crafts acylation reactions using A1C13. Entries 3 and 4 are similar, but include some functionality in the acylating reagents. Entry 5 involves formation of a mixed trifluoroacetic anhydride, followed by acylation in 85% H3PO4. The reaction was conducted on a kilogram scale and provides a starting material for the synthesis of tamoxifen. Entry 6 illustrates the use of bismuth triflate as... 

Entry 5 in Scheme 11.4 is a step in the synthesis of the anticancer drug tamoxifen. Explain why the 2-phenylbutanoyl group is introduced in preference to a trifluoroacetyl group. 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Holleran AL, Lindenthal B, Aldaghlas TA, Kelleher JK (1998) Effect of tamoxifen on cholesterol synthesis in HepG2 cells and cultured rat hepatocytes. Metabolism 47( 12) 1504—1513... 

Tamoxifen (Nolvadex) Antiestrogen agent Inhibits DNA synthesis by binding to estrogen receptors on tumor cells... 

Another application of this chemistry is the asymmetric synthesis of the cyclopropane analog 25 of the breast cancer treatment agent tamoxifen 26 (Scheme 14.2) [53]. The Rh2(S-DOSP)4-catalyzed reaction of phenyldiazoacetate 3 with diarylethylene 23 at... 

Taclamine, 224 Talampicillin, 438 Talopram, 357 Tamoxifen, 127 Tandamine, 347, 460 Tazolol, 110, 268 Teclozan, 28 Temazepam, 402 Terodiline, 56 Tesicam, 379 Tesimide, 296 Testolactone, 160 Tetrahydropyrimidine synthesis, 303 Tetrahydroquinoline synthesis, 371 Tetrazole synthesis, 301,... 

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