Wieland-Miescher ketone
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The Wieland-Miescher ketone is a bicyclic di-ketone (enedione) and is a versatile synthon which has so far been employed in the total synthesis of more than 50 natural products, predominantly sequiterpenoids, diterpenes and steroids possessing exceptionally promising biological properties including anticancer, antimicrobial, antiviral, antineurodegenerative and immunomodulatory activities. Examples of syntheses performed using this ketone as a starting material are that of ancistrofuran and in the Danishefsky Taxol total synthesis.
The most advances in the total syntheses methods starting from Wieland-Miescher ketone were fueled by the search of alternative methods for the industrial syntheses of contraceptive and other medicinally relevant steroids, an area of research that flourished in 1960s and 1970s. Wieland-Miescher ketone contains the AB-ring structure of steroids and is for this reason an attractive starting material toward the steroid skeleton, an approach used in one succesful synthesis of Adrenosterone.
The original Wieland-Miescher ketone is racemic and prepared in a Robinson annulation of 2-methyl-1,3-cyclohexanedione and methyl vinyl ketone. The intermediate alcohol is not isolated.
The required 2-methyl-1,3-cyclohexanedione can be prepared from resorcinol by hydrogenation over Raney nickel to dihydroresorcinol as the enolate followed by alkylation with methyl iodide.
An enantioselective synthesis employs L-proline as a chiral auxiliary in catalytic amounts . This modification is called the Hajos-Parrish-Eder-Sauer-Wiechert reaction .
[edit] References
- ^ Wieland, P.; Miescher, K. Helv. Chim. Acta 1950, 33, 2215.
- ^ Ciceri, Paola, Demnitz, F.W. Joachim, Souza, Márcia C.F. de, Lehmanna, Maik. A Common Approach to the Synthesis of Monocyclofarnesyl Sesquiterpenes. J. Braz. Chem. Soc. 1998, 9, 409-414. ISSN 0103-5053. (Article)
- ^ Wiechert, R. The Role of Birth Control in the Survival of the Human Race. Angew. Chem. Int. Ed. 1977, 16, 506-513.
- ^ Dzierba, C. D.; Zandi, K. S.; Moellers, T.; Shea, K. J. An Ascending Synthesis of Adrenalcorticosteroids. The Total Synthesis of (+)-Adrenosterone. J. Am. Chem. Soc. 1996, 118, 4711-4712.
- ^ 1,6(2H, 7H)-Naphthalenedione, 3,4,8,8a-tetrahydro-8a-methyl-, (S)- Paul Buchschacher, A. Fürst, and J. Gutzwiller Organic Syntheses, Coll. Vol. 7, p.368 (1990); Vol. 63, p.37 (1985). (Article)
- ^ A. B. Mekler, S. Ramachandran, S. Swaminathan, and Melvin S. Newman Organic Syntheses, Coll. Vol. 5, p.743 (1973); Vol. 41, p.56 (1961). (Article)
- ^ 1 H-Indene-1,5(6 H)-dione, 2,3,7,7a-tetrahydro-7a-methyl-, (S)- Zoltan G. Hajos and David R. Parrish Organic Syntheses, Coll. Vol. 7, p.363 (1990); Vol. 63, p.26 (1985) Article Identical reaction with 2-methyl-1,3-cyclopentanedione (5 membered ring instead of a 6 membered ring)
