Gascardic acid

The acetal is used as a protecting group during the reduction of the less reactive ester (guideline 3). The product (12) was used in a synthesis of gascardic acid,... 

Of particular note in comparison with the Wittig procedure is Boeckman s total synthesis of gascardic acid (equation 11). It was found that direct Wittig methylenation was low yielding in the reaction with (36). It was hypothesized that this was because of interference with the two-carbon side chain. The problem was solved by hydrolyzing the esters, followed by addition and elimination of the sulfoximine and reesterification to obtain the desired adduct (37) in 70% overall yield. The Johnson method was also utilized to selectively methylenate the less-hindered ketone (38) in the synthesis of (-)-picrotoxinin (equation 12). ... 

With both alkyl and ester 3-substituents, cyclization occurs on the least hindered side, steric effects or the stability of the product enolates being product determining. Steric effects also dominate the cyclization of the substituted cyclohexadienes (41) and (43) to the spiroketones (42) and (44),76 the cyclization of (45) to (46) en route to gascardic acid,77 and the cyclization of (47) to the norsteroid (48 Scheme 25).78... 

The annulated ring in the intramolecular Diels-Alder/oxy-Cope rearrangement reaction sequence for the preparation of precursor 52 of sesterpene gascardic acid is insufficient for complete stereocontrol in the addition of vinylmagnesium bromide to ketone 52 1 070. 

A third type, including gascardic acid (110), appears to only be known from the insect Gascardia madagascariensis (Hanson, 1972). 

Fig. 22.27. Proposed biosynthesis of ophiobolins and gascardic acid (Hanson, 1972 modified and used with permission of the copyright owner, Academic Press, London).

Boeckmann et al. have completed a synthesis of the sesterterpene gascardic acid (220), using a route in which a Dieckmann cyclization served to construct the seven-membered ring. ... 

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