Total Synthesis of - -Chlorothricolide

Abstracted with permission from J. Ant. Chem. See., 1 4,116, 6457 1994 American Chemical Society 

Carruthers, Cycloaddition Reactions in Organic Synthesis, Pergamon Press, Oxford, 1990. 

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For clarification, individual transformations of independent functionalities in one molecule - also forming several bonds under the same reaction conditions -are not classified as domino reactions. The enantioselective total synthesis of (-)-chlorothricolide 0-4, as performed by Roush and coworkers [8], is a good example of tandem and domino processes (Scheme 0.1). I n the reaction of the acyclic substrate 0-1 in the presence of the chiral dienophile 0-2, intra- and intermolecular Diels-Alder reactions take place to give 0-3 as the main product. Unfortunately, the two reaction sites are independent from each other and the transformation cannot therefore be classified as a domino process. Nonetheless, it is a beautiful tandem reaction that allows the establishment of seven asymmetric centers in a single operation. 

Roush, W.R., and Sciotti. R.J., Enantioselective total synthesis of (-)-chlorothricolide via the tandem inter- and intramolecular Diels-Alder reaction of a hexaenoate intermediate, 7. Am. Chem. Soc., 120, 7411, 1998. 

An impressive sequence involving concomitant inter- and intramolecular Diels-Alder reactions was reported by Roush during the total synthesis of chlorothricolide (63, Scheme 17.11) [48]. When polyunsaturated substrate 58 was allowed to react with chiral enone 59 in the presence of BHT (60)... 

Chlorothricolide, the aglycon of the chlorothricin antibiotic, is a complex molecule containing an octahydronaphthalene unit. Roush and Sciotti [121] recently reported the total enantioselective synthesis of chlorothricolide. The multiple Diels-Alder reaction between poliene 130 and chiral dienophile (R)-131 was the key step in the synthetic process (Scheme 2.50). The interaction... 

In addition, soon after Ireland s synthesis of chlorothricolide analog 228, Yoshii and coworkers [117] made one step further by presenting the synthesis of ( )-chlorothricobde as its 24-O-methyl derivative 251 (Scheme 1.37). Yoshii succeeded in utilizing the same strategy as in the total synthesis of irdnianin for the key... 

Kijanolide 117,76 tetronolide 118,76 and chlorothricolide 119,77 the agly-cones of the structurally novel antitumor antibiotics kijimicin, tetrocaricin A, and chlorothrimicin, are highly valued targets for total synthesis. All three structures share a similar octahydronaphthalene fragment 121, which can be obtained by cyclization of 120. Compound 120, appropriately functionalized 2,8,10,12-tetradecatetraene acid, can be constructed via aldol reactions. Two... 

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