Cyclic P-amino acid

Asymmetric allylic amination of allylic carbonates, prepared from racemic MBH adducts, proceeds in the presence of the Pd catalyst chiral diamino-phosphine oxide (DIAPHOX) (292) and BSA to afford the corresponding chiral aza-MBH adduct derivatives 293 in excellent yield with up to 99% ee. The cyclic reaction products could be converted into various synthetically useful compounds, such as chiral cyclic p-amino acids (Scheme 3.119). ... 

R. erythropolis A4, Rhodococcus sp. R312, and R. erythropolis NCIMB 11540 were used in the hydrolysis of five- and six-membered ahcyclic trans-aminonitriles (Figure 11.6), which are the precursors of cyclic p-amino acids. The enzymes discriminated between the trans- and cis-isomers, the transformation of the former proceeding slowly or stopping at the amide stage. Moreover, hydrolysis of the latter resulted in excellent enantiopurity of the trans-amino acids or amides [38]. 

Of interest is the fact that p-lactamases from Rhodococcus globerulus could be used by Uoyd [66] to hydrolyze enantiomers of P-lactams to yield cyclic P-amino acids with greater than 90% ee. p-Lactamases belong to the P-lactam-recognizing enzymes (BLREs) superfamily. Their active site is characterized by a Ser-Ser-Lys catalytic triad and an oxyanion hole [67], similar to amidase signature enzymes. 

Scheme 19.13 Dynamic kinetic resolution of cyclic P-amino acid derivatives based on amine-catalyzed racemization and enzymatic oxazinone hydrolysis.

Chisholm CD, Fulop F, Forro E, Wenzel TJ. Enantiomeric discrimination of cyclic p-amino acids using (18-crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent. Tetrahedron Asymm. 2010 21 2289-2294. 

Cyclic p-amino acids rearrange to a-methylene lactams upon treatment with acetic anhydride, as shown in eq 11. ... 

Garbay reported the chemoselective reduction of a a-dehydrophenylala-nine substrate bearing a p-acrylate moiety [105]. Robinson et al. have also used a tandem, one-pot asymmetric hydrogenation-hydroformylation-cyclization approach to generate six- to eight-membered cyclic a-amino acids [136]. 

Going back to Miller s synthesis in the flask, one question is why a-amino acids have been obtained and not, for example, p-amino acids, cyclic diketopiperazines, or some other isomers. The answer is important a-amino acids form because they are the most stable products under the selected initial conditions. In other words the formation of those a-amino acids is under thermodynamic control. The same can be said for Oro s synthesis of adenine and other prebiotically low-molecular-weight substances formed in hypothermal vents, or found in space certain molecules and not others form because they are thermodynamically more stable. 

The chiral ligand (44) was prepared starting from the cyclic a-amino acid (S)-proline80). Recently, similar chiral catalysts and related molybdenum complexes involving optically active N-alkyl-P-aminoalcohols as stable chiral ligands and acetylacetone as a replaceable bidentate ligand, were designed for the epoxidation of allylic alcohols with alkyl hydroperoxides which could be catalyzed by such metal complexes 8,). 

Therefore we were interested in the development of a method for the asymmetric synthesis of cyclic and acyclic 5-hydroxy-P-amino acids 83-85 (Fig. 1.3.8). 

O Asymmetric synthesis of protected cyclic 5-hydroxy-P-amino acids. 

The asymmetric aziridination of a, P-unsaturated carboxylic acid derivatives is a direct route to optically active aza-cyclic a-amino acids, and this class of chiral aziridines can also be used as chiral building blocks for the preparation of other amino acids, P-lactams, and alkaloids. Prabhakar and coworkers carried out an asymmetric aziridination reaction of tert-butyl acrylate with O-pivaloyl-N-arylhydroxylamine 25 in the presence of cinchonine-derived chiral ammonium salt 2e under phase-transfer conditions, which furnished the corresponding chiral N-arylaziridine 26 with moderate enantioselectivity (Scheme 2.24) [46],... 

Group VI Donors. The synthesis of complexes of some cyclic tertiary amino-acids with Pd or Pt has been reported (equation ll).36 The complexes are chelated via N and O and have high stability constants, K = 108—1011. Complexes of Pt (Pd, Cu) with 3,3 -diamino-4,4 -dihydroxydiphenylsulphone have been obtained (see p. 387).38... 

List ° and Barbas investigated the effect of different potential catalysts on the reaction of acetone with p-nitrobenzaldehyde (Table 6.11). The important conclusions drawn from this work are that primary and acyclic secondary amino acids do not catalyze the reaction. Cyclic secondary amino acids do catalyze the aldol reaction, the best being proline. Converting proline into either a tertiary amine (A -methylproline) or an amide destroys its catalytic behavior. It is clear that the catalyst must provide both basic and acidic sites. 

One of the invariant amino acids is a unique P-amino acid called Adda (2S,3S,8S,9S)-3 amino-9 methoxy-2,6,8-trimethyl-10-phei5fldeca-4,6-dienoic acid is the most unusual structure in this group of cyanobacterial cyclic peptide toxins). A two-letter suffix (XY) is ascribed to each individual toxin to denote the two variant amino acids (Carmichael 1988). X is commonly leucine, arginine, or tyrosine. Y is arginine, alanine, or methionine. Variants of all the invarianf amino acids have now been reported, e.g., desmethyl amino acids and/or replacement of the 9-methoxy group of Adda by an acetyl moiety. Currently there are in excess of 60 variants of microcystin that have been characterized (Rinehart 1994 Sivonen and Jones 1999). Of these 60 compounds, microcystin-LR would appear to be the microcystin most commonly found in cyanobacteria. It is also common for more than one microcystin to be found in a particular strain of cyanobacterium (Namikoshi 1992 Lawton 1995). The microcystin variants may also differ in toxicity (Carmichael 1993). The literature indicates that hepatotoxic blooms ofM aeruginosa containing microcystins occur commonly worldwide. 

A novel reaction of A-acyl thiazolidinethione enolates with enolizable aldoxime ethers produced thiazolidinethione azetines 1 with excellent diastereoselectivity <03JA3690>. Subsequent addition of an acyl chloride to these azacyclobutene derivatives leads to the formation of the corresponding A -acyl-a,p-disubstituted p-amino acid derivatives, via selective generation of a cyclic four-membered iminium salt. Azetine derivatives were obtained as minor products on irradiating aryl-substituted A-acyl-a-dehydroalanines <03H637>. 

Microcystins are cyclic heptapeptides that share a general structure, as shown in Fig. 1 and Table 1, containing g-hnked D-glutamicacid (d-G1u), D-alanine Co-Ala), p-linked O-erythro-b-methylaspartic acid (o-MeAsp), A-methyldehydroalanine (Mdha), and a unique C20 p-amino acid, (25, 35, 85, 95)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4( ), 6( )-dienoic acid... 

Thus, P-lactam derivatives 47 are formed by the U-4CR from P-amino acids 45 [8, 105-108] (Scheme 4.24). However, the anthranilic acid reacts with aldehydes and isocyanides so that two molecules of each educt are formed, forming eight-membered cyclic products [100b],... 

Scheme 5.4 shows a one-step three-component synthesis of the medicinally important P-lactam 1 by simply mixing a P-amino acid, an aldehyde, and an isonitrile. In this example, the amine and carboxylic acid were tethered together in the form of a P-amino acid. The reaction proceeded according to the Ugi mechanism leading to a cyclic imidate intermediate, which upon intramolecular transacylation afforded the observed cyclic product [14]. 

Microcystins constitute a large family of cyclic heptapeptides with a high degree of homology in the amino acid sequence. As shown in Fig. 4, they are composed of D-Ala in position 1, two variable L-amino acids at positions 2 and 4, the 3-linked D-e/yt/iro-P-methylaspartic acid (MeAsp) in position 3, the novel C20 P-amino acid (25,35,85,95) - 3 - amino - 9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid... 

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