Transform Robinson annelation

The Robinson Annelation transform has received detailed examination by the LHASA group. One subroutine in the table specifically checks to see if there is any functionality alpha to the ketone in the cyclohexane and if there is, remove it by exchanging it for something non-offensive. This subroutine is reproduced below as an example of the CHMTRN language. 

The utilization of the Robinson annellation method for the synthesis of cory-nanthe-type alkaloids has been thoroughly investigated by Kametani and coworkers (149-152). The tetracyclic ring system was efficiently formed via the Michael addition of dimethyl 3-methoxyallylidenemalonate (247) to the enamine derived from 3,4-dihydro-1 -methyl-(3-carboline (150). Alkylation of 248, followed by hydrolysis and decarboxylation, resulted in a mixture of stereosiomeric enamides 250 and 251. Hydrogenation of 250 afforded two lactams in a ratio of 2 1 in favor of the pseudo stereoisomer 253 over the normal isomer 252. On the other hand, catalytic reduction of 251 gave 254 as the sole product in nearly quantitative yield. Deprotection of 254, followed by lithium aluminum hydride reduction, yielded ( )-corynantheidol (255) with alio relative configuration of stereo centers at C-3, C-15 and C-20. Similar transformations of 252 and 253 lead to ( )-dihydrocorynantheol and ( )-hirsutinol (238), respectively, from which the latter is identical with ( )-3-epidihydrocorynantheol (149-151.). 

An alternate route to 90 commenced with the Robinson annelation of the aryl pyruvic acid 97 with methylvinyl ketone followed by dehydration and dissolving metal reduction of the resulting mixture of unsaturated acids to provide the cis-keto acid 98 (Scheme 7) (112b). Transformation of 98 to the rrans-ketal ester 99... 

One of the earliest industrial applications of monoterpenes is in the steroid synthesis. Robinson annelation is used frequently in these transformations as a key step. The first example of this reaction was by Robinson himself to synthesize a-cyperone from dihydrocarvone.56 This synthesis has been shown to follow a stereospecific course to give (+)-a-cyperone (37) from (+)-dihydrocar-vone (38) (Scheme 5.14).57-59 Since then, numerous modifications and improvements have been made to apply this type of reaction for syntheses of a variety of natural and unnatural products.60... 

One of the earliest industrial applications of monoterpenes is in the steroid synthesis. Robinson annelation is used frequently in these transformations as a key step. 

Four ring forming transforms have been considered at length by the LHASA development group - the Diels Alder addition, the Robinson Annelation, the Simmons-Smith reaction, and iodo-lactonization. The first three of these have been fully implemented in LHASA and the fourth is completely flow charted and awaits only coding into the chemistry data base language. 

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