Total organic synthesis

It should be noted that partial or total organic synthesis was used to produce carotenoid oxygenated cleavage products such as, for example, apo-8 -lycopenal (Surmatis et al. 1966). 

It is striking that Diels and Alder finally received the Nobel Prize in chemistry in 1950, more than two decades after their initial publication. The science of total synthesis of natural products was slow to advance and was hindered by World War II. These factors perhaps explain the delay in fuUy appreciating the impact of the Diels-Alder reaction. The modem era of total organic synthesis is generally considered to have started during the 1940s. In 1952, Robert Bums ( R. B. ) Woodward (1917-79) at Harvard would employ the Diels-Alder reaction to brilliant effect en route to total syntheses of the steroids cortisone and cholesterol. 

As mentioned in the previous chapters, the PUFAs and their metabolites have shown a plethora of interesting biological effects. Very often, the PUFA metabolites are available only in minute quantities from their natural sources. Hence, total organic synthesis is necessary not only to provide enough material for biological investigations but also to confirm the... 

Dichloroacetic acid [79-43-6] (CI2CHCOOH), mol wt 128.94, C2H2CI2O2, is a reactive intermediate in organic synthesis. Physical properties are mp 13.9°C, bp 194°C, density 1.5634 g/mL, and refractive index 1.4658, both at 20°C. The Hquid is totally miscible in water, ethyl alcohol, and ether. Dichloroacetic acid K = 5.14 X 10 ) is a stronger acid than chloroacetic acid. Most chemical reactions are similar to those of chloroacetic acid, although both chlorine... 

A detailed procedure for the use of MCPBA recently appeared in Reagents for Organic Synthesis by Fieser and Fieser. The commercially available MCPBA (Aldrich) is 85% pure the contaminant, m-chlorobenzoic acid, can be removed by washing with a phosphate buffer of pH 7.5. The epoxidation is usually performed as follows a solution of 3 -acetoxy-5a-androst-16-ene (2.06 g, 6.53 mmoles) in 25 ml of chloroform (or methylene dichloride) is chilled to 0° in a flask fitted with a condenser and drierite tube and treated with a solution of commercial MCPBA (1.74 g, 20% excess) in 25 ml chloroform precooled to the same temperature. The mixture is stirred and allowed to warm to room temperature. After 23 hr (or until TLC shows reaction is complete) the solution is diluted with 100 ml chloroform and washed in sequence with 100 ml of 10% sodium sulfite or sodium iodide followed by sodium thiosulfate, 200 ml of 1 M sodium bicarbonate and 200 ml water. The chloroform extract is dried (MgS04) and evaporated in vacuo to a volume of ca. 10 ml. Addition of methanol (10 ml) followed by cooling of the mixture to —10° yields 0.8 gof 16a,17a-epoxide mp 109.5-110°. Additional product can be obtained by concentration of the mother liquor (total yield 80-90%). 

Thus, radical denitradon has developed as a reliable tool in organic synthesis and has been mainly carried out using dn hydnde in total syntheses of natural products. There is one report in which NaTeH was used for removing the nitro group. Norslanadione, a biologically acdve... 

On the basis of the examples addressed thus far, it is clear that radical reactions can accomplish manifold transformations in organic synthesis. One of the outstanding achievements of synthetic radical chemistry is the development of synthetic strategies based on controlled, tandem radical cyclizations. The efficiency of such strategies is exemplified in the substantial and elegant synthetic work of D. P. Curran and his group.54 The remainder of this chapter will address the concise total syntheses of ( )-hirsutene [( )-1]55 and ( )-A9(12)-capnellene [( )-2]56 by the Curran group. 

Corey s solution to the intimidating structural and stereochemical complexities of ginkgolide B features an impressive collection of powerful bond-forming strategies. The first total synthesis of ginkgolide B by the Corey group is a major achievement of contemporary organic synthesis. 

Our general survey of palladium in organic synthesis must now come to an end. At the very least, we hope that our brief foray into this fascinating area conveys some of the vitality that characterizes research in this area. The remainder of this chapter will address the first total synthesis of rapamycin by the Nicolaou group. This work is predicated on a novel variant of the Stille reaction. 

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