Cyclic amino acids synthesis

Osipov, S. N., Artyushin, O. I., Kolomiets, A. F., et al. (2001) Synthesis of racemic cyclic amino acids Synthesis of fluorine-containing cyclic a-amino acid and a-amino phosphonate derivatives by alkene metathesis. Fur. J. Org. Chem., 3891-3897. 

Jager and coworkers have used the TBAF catalyzed-stereoselective niho-aldol reaction for the synthesis of cyclic amino alcohols such as iminopolyols, imino sugars, and cyclic amino acids. They are important classes of compounds and have the potential utility as anh-diabetic. 

The application of olefin metathesis to the synthesis of piperidines continues to be widely employed. The use of ring closing metathesis (RCM) in the synthesis of fluorovinyl-containing a,P-unsaturated lactams 148 and cyclic amino acid derivatives 149 is shown below. A key improvement in these reactions is the addition of the Grubbs 2nd generation catalyst (G2) in small portions during the reaction to compensate for catalyst decomposition that occurs at elevated reaction temperatures <06EJOl 166>. 

One of the interesting application of 12 (R= allyl, X=Br) will be the synthesis of cyclic amino acid, (S)-pipecolic acid, as its tert-butyl ester 271251 Monoalkylation of the O Donnell imine 23 with l-chloro-4-iodobutane afforded the alkylated product 26 with 99 % ee. The conversion of 26 to the tert-butyl ester of pipecolic acid 27 was achieved in high yield by the sequence imine reduction, cyclization, and hydrogenolytic removal, as shown in Scheme 8. 

The synthesis of the rare amino acid 3-hydroxy-4-methylproline (8)3 involves an aldol reaction of the oxazoiidinone 5 with methacrolein to provide the a-bromo-0-hydroxy adduct 6. Azide displacement and removal of the chiral auxiliary gives 7. On treatment with dicyclohexylborane, 7 undergoes hydroboration-cycloalkyl-ation to provide, after hydrolysis, the methyl ester hydrochloride (8) of (2S,3S,4S)-3-hydroxy-4-methylproline in >97% de. This cycloalkylation should be a useful route to cyclic amino acids as well as pyrrolidines. 

The procedure can provide a higher amount of L-pipecolic acid in a shorter reaction time than the previously reported system, indicating that it is applicable in industrial production of L-pipecolic acid. A similar system was successfully employed in the enzymatic synthesis of several cyclic amino acids by our group. ... 

Yasuda, M., Ueda, M., Muramatsu, H., Mihara, H. and Esaki, N., Enzymatic synthesis of cyclic amino acids by A-methyl-L-amino acid dehydrogenase from Pseudomonas putida. Tetrahedron Asymmetry. 2006, 17, 1775. 

The same group has exploited this interesting dehydrogenase for the synthesis of cyclic amino acids from linear precursors by developing a one-pot, two-enzyme system (Scheme 2.16). t-Lysine oxidase or L- or d-AAO were initially used to... 

Scheme 2.16 Synthesis of cyclic amino acid (R)-40 by combined use of L-lysine oxidase and NMAADH.

Intramolecular Alkylations. Intramolecular spiroalkylation of the suitably functionalized 5(477)-oxazolone 188 produced 189 in good to excellent yield. Acid hydrolysis of 189 then gave the cyclic amino acid 190 required in the synthesis of the aldose reductase inhibitor sorbinil (Scheme 7.57). ... 

These results prompted them to attempt the stereoselective synthesis of the IV-phenylsulfonyl substituted spiro- (3-lactams 150, 151 (Scheme 36) from the N-(phenylmethyIe ne )be n ze nesulfonamide and the ketene valence tautomer of the bicyclic mesoionic compounds such as (2 S,4/ )-4-acetyloxy or benzoyloxy-IV-acyl-prolines 149 in the presence of acetic anhydride [109]. The presence of the stereocenter in position 4 of the cyclic amino acid 149 was found to be sufficient to ensure complete stereoselectivity on the spiranic C-4. 

Further studies concerning aza Diels-Alder reactions of N-sulfonyl imines have been carried out by Holmes et al. [200] and Whiting et al. [201,202], and the utility of glyoxylato imines for the synthesis of cyclic amino acids has been investigated by Stella s group [203, 204]. An extensive study concerning intramole-... 

Synthesis of N-heterocycies via lactam-derived ketene aminai phosphates. Asymmetric synthesis of cyclic amino acids... 

A remarkable method for the enantioselective synthesis of cyclic a,a-disubstituted amino acids (218 and 220) from natural (5 )-a-amino acids (215) was developed by Kawabata and coworkers (equation 57) . It provides a concise and simple entry to both enantiomers of cyclic amino acids, since the absolute configuration of the newly... 

Iyer, M. S., Gigstad, K. M., Namdev, N. D., Lipton, M. Asymmetric catalysis of the Strecker amino acid synthesis by a cyclic dipeptide. Amino Acids 1996, 11, 259-268. 

The commercially available lactam 76 is usable for amino acid synthesis as a chiral cyclic building block. 4-Fluoro- and 4,4-difluoro-3-aminocyclopentane carboxylic acids 79 and 81, potential inhibitors of y-aminobutanoic acid (GABA) aminotransferase, were synthesized as shown in Scheme 9.19 [39]. In this process, replacement of hydroxyl or carbonyl groups with fluorine was achieved by the use of DAST. Interestingly, the stereochemistry in substitution with DAST is retained [40], although it is by inversion in most cases [26]. Hydrolysis of 78 gave 80. 

Between 1899 and 1908, Fischer turned his attention to proteins. He developed methods to separate and identify individual amino acids and discovered an entirely new class, the cyclic amino acids (those with ring structures). Fischer also worked on protein synthesis from the amino acids. He demonstrated the nature of the peptide bond and discovered how to make small peptides in the laboratory. 

The reaction of carboxylic acids with the PhI(OAc)2-iodine system may result in a decarboxylation ieading to the intermediate formation of a carbon-centered radical, which can be further oxidized to a carbocation and trapped by a nucleophile. This process has been utilized in several syntheses [97, 615,616, 617]. In a typical example, the oxidative decarboxylation of uronic acid derivatives 568 in acetonitrile under mild conditions affords acetates 569 in good yields (Scheme 3.225) [615]. A similar oxidative decarboxylation has been be used for the synthesis of 2-substituted pyrrolidines 571 from the cyclic amino acid derivatives 570 [616,617]. 

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