L-Pyroglutamic acid

Enantiospecific syntheses of amino derivatives of benzo[ ]quinolizidine and indolo[2,3- ]quinolizidine compounds have also been achieved via A-acyliminium ion cyclization reactions, as an alternative to the more traditional Bischler-Napieralski chemistry (see Section 12.01.9.2.2). One interesting example involves the use of L-pyroglutamic acid as a chiral starting material to construct intermediates 240 via reaction with arylethylamine derivatives. Diisobutylaluminium hydride (DIBAL-H) reduction of the amide function in 240 and subsequent cyclization and further reduction afforded piperidine derivatives 241, which stereoselectively cyclized to benzo[ ]quinolizidine 242 upon treatment with boron trifluoride (Scheme 47) <1999JOC9729>. 

HE Klieger. On peptide synthesis I. Synthesis of glutamic acid peptides using car-bobenzoxy-L-pyroglutamic acid. Justus Liebig s Ann Chem 640, 145, 1961. 

An angiotensin-converting enzyme inhibitor 64 was prepared in several steps from L-pyroglutamic acid. The formation of the bicyclic system was achieved with methylene glutaric anhydride (89TL3621). 

In connection with the enantioselective alkylation of Pro or 4-hydroxy-proline, the azabicyclo[3.3.0]octane system 81 was obtained after reaction with pivaldehyde (81HCA2704 85HCA155). In a more complex transformation A-protected L-Pro was transformed into the same bicyclic system (Scheme 49) (81JA1851 84JA4192). The product was prepared as a model substance in the total synthesis of pumiliotoxin. A related compound 82 was prepared from 5-(hydroxymethyl)-2-pyrrolidinone (prepared from L-pyroglutamic acid) by an acid-catalyzed condensation with benzaldehyde (86JOC3140). 

In the synthesis of the alkaloid gephyrotoxin, L-pyroglutamic acid was used as a starting material for the preparation of intermediate 85 (81TL4197). A related pyrrolooxazine 86 was also obtained from pyroglu-tamic acid after A-substitution and ring closure in the presence of silica... 

For the synthesis of (+)-preussin, commercially available L-pyroglutamic acid (154) could serve as an enantiomerically pure starting material. Given the key reaction we had in mind, the bond set for the synthesis of preussin was straightforward (Scheme 40). Attachment of the alkyl chain to the core... 

Two conceptually different approaches to the tra 5-4-cyclohexylproline fragment have been disclosed by the Squibb process group. The first route relies on a stereoselective alkylation for installation of the cyclohexyl substituent (Thottathil et al., 1986). L-Pyroglutamic acid (62) was reduced using literature methods to give the hydroxymethyl... 

The step 4 product was also amidized with L-pyroglutamic acid and naphthylen-2-yl... 

Precatalyst 19 was built up from cheap L-pyroglutamic acid (21) in a short and easy synthesis sequence involving a one-pot variant developed by Rovis et al. to form the triazolium core (Scheme 9.4) [36]. The synthesis of 20 started from a-tetralone (22), which was stereo selectively converted to the polycyclic y-lactam 23 with inexpensive (R)-phenylglycinol as chiral source. After cleavage of the auxiliary, the one-pot-procedure that had already been used before yielded the triazolium salt 20 (Scheme 9.5). 

Somfai et al. demonstrated that it is also possible to use A-sulphonyl groups (Somfai and Ahman 1992 Ahman and Somfai 1992 Weinreb 1997) using the same concept for the cyclization step developed by Speckamp with the allylsilanes (Esch et al. 1987). In this case, the starting product was the L-pyroglutamic acid, inside the succinimide (Esch et al. 1987), allowing the enantioselective synthesis of the (+)-anatoxin-a. The key step consisted of an intramolecular cyclization of an 7V-tosyl iminium ion, catalysed by a Lewis acid, TiCl, to set up the desired bicyclic ring system (Somfai and Ahman 1992). 

Recently, a new attempt to synthesise (+)-anatoxin-a was published by Tanner and co-workers (Hjelmgaard et al. 2005). They transformed the L-pyroglutamic acid into the intermediate 61 (Scheme 7.14), performing some improvements for achieving the lateral chain with the a,p-unsaturated ketone compared with the Speckamp (Melching et al. 1986) and Somfai (Somfai and Ahman 1992) approaches. They carried out the cyclization of 61 under Speckamp and Hiemstra conditions, also used by Somfai. 

The (+) form of the alkaloid gephyrotoxin (198) was synthesized through a series of reactions starting with L-pyroglutamic acid (192), which was converted to the nitrile (193). Treatment of this with P2S5,... 

C5H7N03 L-pyroglutamic acid 98-79-3 25.00 1.2175 2 4932 C5H803 3-methyl-2-oxobutanoic acid 759-05-7 20.00 0.9968 1... 

Somfai and Ahman have applied an intramolecular allyl silane addition to an AT-sulfonyl iminium ion as a key step in an alternative synthesis of (+)-anatoxin A [43]. Thus, L-pyroglutamic acid-derived compound 55 was homologated to aldehyde 126 and then to allyl silane 127 (Scheme 24). Using titanium tetrachloride, 127 could be cyclized in good yield to bicyclic olefin 128, which was converted to the alkaloid. 

L-Pyroglutamic acid Ethylamine FIGURE 16.5 Reaction of L-pyroglutamic acid with ethylamine to form L-theanine. 

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