Phaseolinic acid

Renaud and co-workers used 78 for the synthesis of (-)-phaseolinic acid (6) and (-)-pertusarinic acid (8) (Scheme 12) [32, 33]. Radical addition of dimethyl phenylselenomalonate to 78 proceeded with rearrangement of the bicyclics to yield the seleno-acetal 79 [34]. After reductive deselenylation and Baeyer-Villiger oxidation treatment of 80 with BU4NI and BBr3 led to a simultaneous cleavage of the ether, the lactone, and the methyl ester func-... 

The required side-chain for (-)-pertusarinic acid (8) was introduced by a mixed Kolbe electrolysis with 85 [36], elegantly demonstrating the value of this process for natural product synthesis in the presence of various functional groups. In an analogous way (-)-phaseolinic acid (6) was synthesized by reacting pentanoic acid in a mixed Kolbe electrolysis with 84 to 88. 

Strategy should also be applicable to paraconic acids, and indeed, the synthesis of (+)-phaseolinic acid (6) as well as (-)-methylenolactocin (11) has successfully been achieved this way (Scheme 24) [61]. This approach is especially advantageous if the precursors are readily available on large scale to compensate for the principle loss of at least 50% caused by the presence of the undesired enantiomer. Thus, a mixture of the lactones ( )-151 and ( )-152 is available in a single step from the ketodiester 150 [5c, 62] via a reduc-tion-lactonization sequence. After separation, ( )-151 was transformed into racemic ( )-153, which was hydrolyzed by pig liver esterase (PLE) to yield (+)-phaseolinic acid ((+)-6) in up to 94% ee. Alternatively, the remaining (-)-153 could be obtained in up to 96% ee, which could be hydrolyzed to (-)-phaseolinic acid ((-)-6). 

The utility and efficiency of this methodology is demonstrated by the first catalytic asymmetric synthesis of (—)-phaseolinic acid , a natural product displaying useful antifungal, antitumor and antibacterial properties, as illustrated in equation 110. 

Grignard reagents such as 66a have been successfully added to a,p-iuisaturated thioesters 67 in the presence of the Cu/JOSIPHOS catalyst (Scheme 11.26) with high enantioselectivity. The diastereoselectivity for the second aldol process was controlled by the bulkiness of the substituent of the enolate at the y-position. This methodology has served for the synthesis of phaseolinic acid, a paraconic acid derivative with... 

Alkene and Alkyne Metathesis Phaseolinic Acid (Selvakumar), Methyl 7-Dihydro-trioxacarcinoside B (Koert), Arglabin (Reiser) and Amphidinolide V (Fiirstner)... 

AsN. Selvakumar of Dr. Reddy s Laboratories, Ltd., Hyderabad approached (reira/iedron Lett. 2007,48, 2021) the synthesis of phaseolinic acid 6, there was some concern about the projected cyclization of 2 to 3, as this would involve the coupling of two electron-deficient alkenes. In fact, the Ru-mediated ring-closing metathesis proceeded efficiently. The product unsaturated lactone 3 could be reduced selectively to either the trans product 4 or the cis product 5. 

Ariza et al. utilized the TST-RCM in conjunction with the Ireland-Claisen rearrangement to facilitate the total synthesis of (—)-phaseolinic acid (Scheme 8.3) [14]. The C2-symmetrical silaketal 6 was prepared in 58% overall yield using an adaptation of the protocol described by Evans and Murthy [13], which employed enantiomerically enriched propargylic alcohols to form the symmetrical bis-alkoxysilane rather than allylic alcohols. Selective reduction of the his-alkyne with Lindlar catalyst, followed by RCM with catalyst [Ru]-I, afforded the silaketal... 

Phaseolinio acid (10) Scheme 8.3 Asymmetric synthesis of (—)-phaseolinic acid. 

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