Quinic acid synthesis

Pollini and colleagues converted D(—)-quinic acid in five steps into a chiral oxime 395, R = H in an enantiomeric pure form and subjected this oxime to a Beckmann rearrangement (equation 161). Even though the reaction lacked selectivity, 395 was useful in the synthesis of the chiral epoxide 396, a key intermediate in the synthesis of (—)-Balanol 397. The same authors also prepared the isomeric epoxide 398. 

During the total synthesis of Dragmacidin F (537) from quinic acid, Stoltz and col-leagues applied a high-yield late-stage Neber rearrangement to introduce in a completely enantioselective manner an amino group into a complex framework (equation 238). 

Scheme 7.2. Synthesis of epoxide 9 from (—)-quinic acid (15).

Inhibition of Chorismate Synthase Shikimic and quinic acids are used by microorganisms, fungi, and superior plants for the synthesis of essential aromatic amino acids from acyclic sugars. Fluorinated analogues of substrates and reaction intermediates have been synthesized in order to inhibit enzymes involved in... 

The availability of ctetq) advanced synthons that carry the required chirality is an advantage, particularly in projects aimed at industrial total synthesis. Natural products are often used as synthons, ideally fi om a renewable source, such as microbial fermentations. In a few cases, biotechnology has become an ahemative source. The total theses of the antitumor agent esperamicin A and the immunosuppressant FK-506 are exanq>les. In both cases, the synthon was quinic acid (Barco 1997), cheaply obtained by biotechnology (Chapter 14.1.e) rather than fi om the environmentally noxious extraction fi om the bark of Cinchona spp. Used to build up combinatorial libraries, quinic acid has gained further inq)ortance in organic thesis (Phoon 1999). 

Barco, A. (1997) D-(-)-Quinic acid a chiron store for natural product synthesis. Tetrahedron Asymm., 8, 3515-45. 

Phoon, C. W. Abell, C. (1999) Use of quinic acid as template in solid-phase combinatorial synthesis. J. Comb. Chem., 1,485-92. 

Geometrical (cis-trans) isomers of benz-omorphans result from the cyclization step in their synthesis when the bond to C-6 is formed (Scheme 2). When this is considered a transaddition to the double bond the preponderance of the cis or form is easily explained (10). Resolution of optical isomers from both cis and trans forms has been reported (7,19.20). The norpentazocine precursor in the cis form crystallized first as the (-) base with (+) tartaric acid which would give the twenty-fold more active (-) pentazocine. The (+) base (-) tartarate was recovered from resolution liquors. Quinic acid salts were formed for resolution of the trans isomers. 

Several other important compounds found in the common aromatic amino acid pathway whose overproduction has been studied are shikimic acid (61) and, to a lesser extent, quinic acid (62) (Scheme 19.41).323 Both 61 and 62 are naturally occurring, highly functionalized carbocyclic rings with asymmetric centers, which can be used as starting material for the synthesis of GS4104 (63), a neuraminidase inhibitor discovered by Gilead Sciences and developed by Roche Pharmaceuticals under the trade name of Tamiflu .324 325 Manipulation of the aromatic amino acid pathway in E. coli has allowed for numerous strains to be assembled that produce both 61 and 62 as well as other intermediates.326 327 As reported by Chandran and co-workers, an E. coli strain has been constructed that synthesized 87 g/L (0.5m) of 61 in 36% (mol/mol) yield with a maximum productivity of 5.2 gL- lr1.328... 

The synthesis of 6a-carba-p-D-ffuctopyranose (165) (Scheme 26) comprised four key steps, namely the inversion of C4 configuration in quinic ester 160 to obtain 161, the shift of the ketal protection from C5-C6 to C4-C5 to provide 162, the stereocontrolled dihydroxylation of epi-shikimate 162, and the C6-deoxygenation reaction of advanced intermediate 164. Carbasugar 165 was obtained in an overall 12% yield from quinic acid 159 for a 13-step sequence. 

Barco, A. et al. D-(-)-Quinic Acid a Chiron Store for Natural Product Synthesis. 1997 [85]... 

Jiang, S. et al. Synthesis of 3-Deoxy-3,3-difiuoroshikimic Acid and Its 4-Epimer from Quinic Acid. 3.3 1999(131]... 

Maycock, C D. et al. An Application of Quinic Acid to the Synthesis of Cyclic Homochiral Molecules A Common Route to Some Interesting Carbocyclic Nucleoside Precursor. 2.4 1993 [151]... 

Shing, T.K.M. et al. (-)-Quinic Acid in Organic Synthesis. 3. Stereocontrolled Syntheses of Pseudo-a-D-glucopyranose and Pseudo-a-D-mannopyranose. 3.1 1992 [60]... 

Scheme 29. Synthesis of an enantiomerically pure diene building block 107 starting from (-)-quinic acid [87]...

The PLE-catalyzed asymmetric hydrolysis of /neso-l,3-cts-3,5-cij-l,3-diacetoxy-5-benzyloxycyclohexane afforded (lS,35,5/f)-l-acetoxy-5-benzyloxycyclohexan-3-ol, which could be used as chiral building block for the synthesis of the compactin lactone moiety and quinic acid (eq 4). ... 

Hanessian, S, Reddy, G V, Huynh, H K, Pan, J, Pedatella, S, Ernst, B, Kolb, H C, Design and synthesis of sialyl Le mimetics based on carbocyclic scaffolds derived from (-) quinic acid, Bioorg. Med. Chem. Lett, 1, 2729-2734, 1997. 

Molin, H., and Pring. B.G., Regio- and stereoselective synthesis of the carbocychc analogue of 3-deoxy-P-D-mann-2-octulopyranosonic acid (P-KDO) from (-)-quinic acid. Tetrahedron Lett., 26, 677, 1985. 

The quinic acid derived 2,5,6-trideoxystreptamine analogs 61 was used to prepare 5,6-dideoxyneamine (62) hiosynthetically from Streptomyces fradiae [49]. The crucial intermediate for synthesis of 61 was the hydroxyketone 55, which is readily available from quinic acid. Treatment of 55 with p-toluenesulfonyl chloride in pyridine gave enone 56, which after catalytic hydrogenation generated the saturated ketone 57. Stereoselective reduction of 57, followed by tosylation, furnished deriv-... 

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