Coronafacic acid, synthesis

This reaction has been applied to the elaboration of steroid skeletons and to sarkomycin (a natural product which shows inhibitory effect on Ehrlich ascites tumor) synthesis. Coronafacic acid synthesis is another interesting example of a palladium-catalyzed cyclization. 

Coronafacic acid, a bacterial toxin, was synthesized using a key step that involves three sequential pericyclic reactions. Identify them, and propose a mechanism for the overall transformation. How would you complete the synthesis ... 

Intramolecular 2 + 2 cycloaddition.b A recent synthesis of coronafacic acid (4) proceeds through a cyclobutene (2) to obtain a trienone (3), the immediate precursor ot 4 11 rider the most satisfactory conditions, A1C13 in CH2C12 at 25°, the yield of this Inlramolucular cycloaddition is only 16%. However, since the remaining steps to 4 call he conducted without purification of the intermediates, the overall yield for a rallier lengthy synthesis is reasonable. 

Recently, Charette and coworkers reported on a similar approach to -hydroxy esters (equation 46) in their synthesis of ( )-coronafacic acid, a natural component of the phytotoxin coronatin. They studied the effect of various aldehydes on the diastereoselectivity... 

The application of the Michael addition of phosphonate esters in the synthesis of coronafacic acid was reported by Shibasaki and coworkers and is outlined in Sch. 61 [89]. The Michael adduct ent-427 was prepared in 94 % ee in the same fashion as its enantiomer 427 (Sch. 59) by employing a catalyst prepared from (5)-BINOL. 

All the carbons of the target were introduced by a Horner-Wadsworth-Emmons reaction of ent-427 with a-ethylacrolein, which gave a mixture of ( ) and (Z) olefins 437. The synthesis of the E) isomer of 437 constitutes a formal synthesis of coronafacic acid because its conversion to the natural product has been reported by Nara, Toshima, and Ichihara [90]. They reported that 437-E could be cyclized with base to hydrindenones 438 and 439 in 71 % yield. After purification, the major diastereomer 438 could be hydrolyzed to coronafacic acid in 95 % yield. 

The a-silyl caibanions necessary to tqiply the Peterson reaction to higher substituted examples are limited by the ability to efficiently produce the anion. A clever example of an altenuitive to the Wittig reaction for ethylidene formation to give (285) with a-(trimethylsilyl)vinyllithium was utilized by Jung in the synthesis of coronafacic acid (Scheme 40). ... 

Fig. 8. Stereoselective synthesis of coronafacic acid (31) through retro Diels-Alder and electrocyclic reactions...

This astonishing behavior of ALB was also very useful for the efficient synthesis of the natural products coronafacic acid (Scheme 6.100) [123], tubifolidine (Scheme 6.101) [124], and ll-deoxy-PGFja (Scheme 6.102) [125]. 

As Cope substrates derived from 5 are highly reactive, aromatic double bonds can also be involved in the rearrangement. Thus, steroid analogs can be prepared from a-naphthyl derivatives 291060, and the benzofuran derivative 31 is used in the synthesis of coronafacic acid 638, 1066. 

There are several important applications of the Mo-carbene complex (1) in the synthesis of natural products, illustrating the power of the ring-closing olefin metathesis. Thus, elegant syntheses of coronafacic acid, dactylol, and fluvirucin have been reported. 

One of the first examples of the use of the aromatic-Cope rearrangement in synthesis was developed in the Jung laboratories toward the synthesis of ( )-coronafacic acid. Featuring the participation of a benzofuran as the aromatic partner in an anionic oxy-Cope rearrangement, the reaction of 249 proceeds to give the tetracyclic product 250 as a single diastereomer. 

Yates P, Bhamare NK, Granger T et al (1993) Tandem Wessely oxidation and intramolecular Diels-Alder reactions. IV. The synthesis of (it)-coronafacic acid. Can J Chem 71 995-1001... 

Synthesis of the naturally occurring unsaturated acids sarkomycin, ( ) methylenomycin A, and ( ) coronafacic acid have appeared. The metabolites of arachidonic acid provide an area of natural products chemistry in which total synthesis is playing a vital role. Corey and his co-workers report impressive advances involving synthesis as a means of structural proof, and of stereospecific synthesis to provide large quantities of natural products only available in trace amounts. The synthesis of some oxidation products of arachidonic acid has also appeared. ... 

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