Cancer natural products

K, Watanabe, H., Nishikawa, K, Kitahara, T., and Osada, H. (2004). The anti-cancer natural product pironetin selectively targets Lys352 of a-tubulin. Chem. Biol. 11, 799-806. 

Kuwajima employed the fragmentation of cyclopropyl ketone 21 to introduce the Cl 9-methyl group in an approach to the anti-cancer natural product paclitaxel (Taxol) treatment of 21 with Sml2 gave enol 22 in quantitative yield (Scheme 4.12).22... 

Mukaiyama s 1999 approach to the anti-cancer natural product paclitaxel (Taxol) involved construction of the B ring using a Sml2-mediated Refor-matsky reaction.68 Treatment of 69 with Sml2 at -78 °C gave the product 70 in high yield and with good diastereoselectivity (Scheme 7.29). 

Fig. 1.5 Marine anti-cancer natural product halichondrin B and eribulin analogue...

Figure 11 Antiinflammatory or anti-cancer marine natural products and synthetic analogs that are in commercial use or in clinical and preclinical evaluation...

The majority of promising drug candidates emerging from marine natural products research to date are potential cancer treatments. Six anti-cancer compounds that are either marine natural products or synthetic analogs of marine natural products have made it to clinical trials. The first of these compounds to enter clinical trials was didemnin B (43), one of a family of cyclic depsipetides isolated from the Caribbean tunicate Trididemnum solidum Didemnin B was advanced to Phase II clinical trials for treatment of small cell lung cancer, myeloma, prostate cancer, and melanoma. Unfortunately, no favorable responses were found so the compound has been withdrawn. Crude extracts of another Caribbean tunicate, Ecteinascidia turbinata, showed extremely... 

Camptothecin was discovered as an active anticancer drug isolated from the bark of Camptotheca acuminata. The anticancer activity of camptothecin was discovered in the 1960s by the National Cancer Institute (NCI) as part of a systematic effort to screen for novel anticancer agents derived from natural products. Monroe Wall and Mansuhk Wani identified the chemical structure of camptothecin. They also identified the chemical structure of taxol, again under the auspices of the NCI. Susan Hoiwitz was contracted by the NCI to elucidate the anticancer mechanisms of camptothecin. She found in the early 1970s that camptothecin induced DNA breaks and attested DNA and RNA synthesis. However, it is approximately 12 years later, only after DNA topo-isomerase I (Topi) had been identified in human cells, that Leroy Liu and his coworkers found that Topi was the cellular target of camptothecin [reviewed in [1]. 

In nearly every pharmacy, supermarket, and health food store, you can find bottles of antioxidants and antioxidant-rich natural products, such as fish oils, Gingko biloba leaves, and wheat grass. These dietary supplements are intended to help the body control its population of radicals and, as a result, slow aging and degenerative diseases such as heart failure and cancer. 

Figure 3.3. Bryostatin 2. Bryostatin 2 (C HggOjg) is a biologically active marine natural product which may have useful anti-cancer properties. It was recently synthesised at Harvard by Professor David Evans and his research group. In this illustration, all of the hydrogen atoms are omitted in order to simplify the structure. The lower diagram shows a low energy conformation of bryostatin 2, but it may only be a local minimum and not a global minimum. Many other conformations are accessible at room temperature.

Mickel, S.J., Sedelmeier, G.H., Niederer, D. etal. (2004) Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (-P)-Disco derm olide. Part 1 Synthetic Strategy and Preparation of a Common Precursor. Organic Process Research Development, 8, 92-100. 

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