Paraconic acid

The synthetic utihty of the above transformations stems from the fact that many monoesters obtained as a result of hydrolysis may be converted to pharmaceutically important intermediates. For example, the optically active glycerol derivative (27) is a key intermediate in the production of P-blockers. Akyl derivative (25) may be converted into (5)-paraconic acid [4694-66-0] ((5)-5-oxo-3-tetrahydrofurancarboxyhc acid) that is a starting material for the synthesis of (3R)-A-factor. The unsaturated chiral cycHc monoacetate (31) is an optically active synthon for prostaglandins, and the monoester (29) is used for the synthesis of platelet activating factor (PAF) antagonists. 

Para-chinon, n. paraquinone, p-quinone. -con-sdure, /. paraconic acid, -cyan, n. paracy-anogen. -cymol, n. paracymene, p-cymene. Paradies, n. paradise, -apfel, m. tomato, -feige, /. banana, -holz, n. agalloch, aloes wood, -koraer, n.pl. grains of paradise, paradox, a. paradoxical. 

Bandichhor R, Nosse B, Reiser O (2005) Paraconic Acids - The Natural Products from Lichen Symbiont. 243 43-72 Bannwarth W, see Horn J (2004) 242 43-75 Barre L, see Lasne M-C (2002) 222 201-258... 

Enantioselective, Chiral Pool-Based Syntheses of Paraconic Acids. 49... 

Lichens, the natural source of paraconic acids [1], are a successful alliance between fungi and algae. Each is doing what they do best, and thriving as a... 

Paraconic Acids - The Natural Products from Lichen Symbiont... 

Consequently, a number of stereoselective syntheses have been developed leading to a variety of paraconic acids either in racemic or in enantiopure form, using starting materials from the chiral pool, chiral auxiliaries or applying catalytic asymmetric methodology. Moreover, a number of strategies leading to paraconic acids in a non-stereoselective way have been reported, which will not be described in detail in this review [4, 5]. 

The norbornene derivative 16, obtained exclusively as the exo adduct via a Diels-Alder reaction of itaconic anhydride with cyclopentadiene followed by hydrolysis and esterification [7], was found to be a suitable precursor for an enolate of type 14 (Scheme 2). Due to the quaternary center at C-3 eno-lization with base proceeded unambiguously, giving rise to a diastereomeric mixture of lactones 17/18 after reaction with hexanal. Retro-Diels-Alder reaction led to the monocyclic lactones 19/20 (2 1), elegantly unmasking the cxo-methylene group found in so many paraconic acids [8]. Hydrolysis of this mixture in refluxing butanone with 6 N HCl [9] effected epimerization... 

Chiral butenolides are valuable synthons towards y-butyrolactone natural products [37] and have also been successfully applied to the synthesis of paraconic acids. The lactone 91, readily available from the hydroxyamide (rac)-90 by enzymatic resolution [38] followed by iodolactonization, proved to be an especially versatile key intermediate. Copper(I)-catalyzed cross coupling reactions with Grignard reagents allowed the direct introduction of alkyl side chains, as depicted in 92a and 92b (Scheme 13) [39, 40]. Further... 

Enantioselective, Chiral Auxiliary Based Syntheses of Paraconic Acids 2.3.1... 

Functionalized y-acyloxy-a,yS-unsaturated esters provided yet another versatile strategy towards paraconic acids as exemplified with the synthesis of protolichesterinic acid ((-i-)-lO) (Scheme 22) [60]. The prerequisite precur-... 

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). 

Based on this approach, several paraconic acids became available [65]. A formal synthesis of (-)-methylenolactocin (11) was accomplished by the addition of 1,3-pentadienyltrimethylsilane (161) to the aldehyde 156 (Scheme 26). 

For the synthesis of paraconic acids being substituted with alkyl chains of various lengths the lactones 163 were employed (Scheme 27). It was envi-... 

The application of tungsten-<7r-allyl complexes provided yet another elegant and efficient access to paraconic acids (Scheme 29) [68]. The propargylic al-... 

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