Gibberellic acid synthesis

A 2-methoxyethoxymethyl ether was used to protect one phenol group during a total synthesis of gibberellic acid. 

A second route to the key tricyclic intermediate A for the synthesis of gibberellic acid was also developed (Ref. 8) ... 

Retrosynthetic analysis of antheridic acid produced a totally different plan of synthesis from that which had been employed for the structurally related target gibberellic acid. The synthesis of antheridic acid, which included a number of novel steps, allowed definitive assignment of structure and revised stereochemistry at C(3). 

Scheme 6. Corey s synthesis of gibberellic acid GA3 (22) employing the Upjohn catalytic dihydroxylation procedure.

In a synthesis of gibberellic acid, a diene and quinone, both with oxygen-substituted side chains, gave the initial intermediate. Later in the synthesis, an intramolecular D-A reaction was used to construct the A-ring. 

H NMR and infrared spectral data of ( )-B, ( )-B methyl ester, and ( )-B methyl ester 3-benzoate were identical with those of AAn and the corresponding derivatives. Mass spectra of the methyl esters of ( )-B and AAn were identical. Chromatographic mobility of ( )-B relative to gibberellic acid (GA3) (as standard) was identical with that reported for AAn. Therefore, this synthesis also proved that antheridium inducing factor, AAn, must be regarded as possessing stereostructure B rather than A as originally supposed. 

A number of papers on the biological activity of gibberellins and their derivatives have appeared. The stimulation of plant mRNA synthesis by gibberellic acid has been noted. 

Alkylation of the enolate of a carboxylic acid, formed as an intermediate in the Birch reduction of an aromatic acid, has been successfully exploited in synthesis, e.g., in the synthesis of gibberellic acid. A model compound 24 was reduced with sodium in diethyl ether-liquid ammonia and the resulting carbanion was alkylated with iodomethane to give 25 in ca. 80% yield87. 

It is surprising that so little basic work concerning the relationship of gibberellic acid to enzyme function and synthesis has been reported. The field of study is very fertile and should be extremely rewarding for an individual who wishes to investigate some of the basic plant growth-regulating processes. 

During studies directed towards a total synthesis of gibberellic acid, the lactone 1 was heated under reflux with potassium t-butoxide in t-butanol. Acidification of the reaction mixture and separation of the products gave compound 2 as the major product (30%). 

Diels-Alder reaction with cyclopentadienes. An improved synthesis of a key intermediate (6) to gibberellic acid (7) begins with the cycloaddition of 1 to a 2 1 mixture of 2- and l-(2-bromoallyl)cyclopentadiene (2) to give the adduct 3 in which the acetyl group has the enr/o-orientation. The silyl enol ether of 3 when heated undergoes a Cope rearrangement to give a eis-hydrindene (4), which was converted... 

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