Coronamic acid

Figure 3 Nonprotein amino acids (a) 5,5,5-trichioroieucine, (b) coronamic acid, and (c) 4-OH-phenylglycine.

During the biosynthesis of nonribosomal peptides, there are two ways to incorporate the nonprotein amino acids. They can be incorporated either as a single unit or as an L-a-amino acid, which then undergoes structural modifications, while attached to the carrier protein. In the case of coronamic acid, L-rr//o-isoleucine is loaded onto the carrier protein and a unique biosynthetic pathway produces a cyclopropyl group containing a nonprotein amino acid. Specific examples of the biosynthesis of nonprotein amino acids will be discussed in the following sections. 

This section focuses on the nonprotein amino acids containing alkyl or haloalkyl groups as side chains. There are number of examples containing linear and branched alkyl chains, such as ethyl, propyl, and t-butyl. Some amino acids contain the cyclopropyl group as side chains (coronamic acid derivatives and BZR-cotoxin 11). Furthermore, dysamides, a class of diketopiperazines, contain nonprotein amino acids with chlorinated alkyl side chains. ... 

With the use of gene clusters of the natural products coronatine and kutznerides, the biosynthetic pathway of coronamic acid has also been elucidated by Walsh and coworkers. From the biosynthetic analyses, a nonheme Fe -dependent halogenase was identified as the chlorinating enzyme that converts L- //a-isoleucine to 7-chloroisoleucine. A second enzyme carries out a dehydrochlorination reaction to yield coronamic acid. The general biosynthetic pathway is shown below (Scheme 7). 

Scheme 7 The biosynthetic pathway for coronamic acid attached to the carrier protein. ...

The total asymmetric syntheses of natural (lS,2S)-norcoronamic 72a and of (lS,2S)-coronamic acid 73 have been obtained from the diastereoselective cyclization of chiral non-racemic 2-(Ar-benzylideneamino)-4-chlorobutyronitriles [98] but one of the shortest syntheses of these attractive amino acids was based on the diastereoselective palladium(0)-catalyzed alkylation and S cyclization of l,4-dichlorobut-2-ene by the anion of 2-aminoacetonitrile derivatives [99]. On the other hand, diastereoselective palladium(0)-catalyzed azidation of chiral non-racemic 1-alkenylcyclopropyl esters provide non-natural (lk,2S)-norcoro-namic acid, enantiomerically pure [100]. 

Thus hydrogenolysis of coronamic acid (505) led to a mixture of isoleucine, allo-isoleucine, norleucine and 2-amino-2-methylvaleric acid this demonstrates, that all... 

IR-Coronamic acid (505) and U -allocoronamic acid (649) were more effectively converted to the 1-malonyl derivative than the two IS-stereoisomers From this stereoselectivity it was deduced that aminocyclopropanecarboxylic acid (6) is recognized as a D-amino acid by malonyl transferase. For resolution of racemic 2-alkyl-1-aminocyclopropane-1-carboxylic acids see Refs 27, 33, 752. 

This method was utilized for the synthesis of the four stereoisomers of coronamic acid [17]. The ( )-allylic (3-D-glucopyranoside 3 was cyclopropanated under Simmons-Smith conditions at — 30°C with high diastereoselectivity (>100 1). The reaction of the corresponding (Z)-allylic... 

SCHEME 10.2 Application of glucose-directed cyclopropanations to the preparation of coronamic acid and aHo-coronamic acid. 

Charette, A B, Cote, B, Stereoselective s3mthesis of all four isomers of coronamic acid a general approach to 3-methanoamino acids, J. Am. Chem. Soc., 117, 12721-12732, 1995. 

Further recent MS applications to investigate substrate specificity were the characterization of aminoacyl-transferase CmaE in coronamic acid biosynthesis pathway106 (Figure 21(a)). Purified CmaE transferred various chemically differing aminoacyl groups between various T domains, which were detected by MALDI-TOF MS, and therefore CmaE promiscuity was identified (Figure 21(b)). 

Figure 21 Characterization of aminoacyl transferase CmaE in coronamic acid biosynthesis pathway, (a) Within the biosynthetic pathway, CmaE carries out substrate shuttling from theCmaAT domain to the CmaDT domain, (b) CmaE substrate tolerance was characterized by MALDI-TOF MS (observed and calculated mass shift of CmaD in the table). In addition, evidence of reversible aminoacyl transfer by CmaE was detected.

Figure 26 Cyclopropane ring formation by CmaC in coronamic acid biosynthesis, (a) Characterization of 7-CI loss by ESI-FTMS. (b) Characterization of a-H exchange by deuterium solvent exchange and PEA. CmaC promotes deuterium incorporation at a-C position, (c) Proposed cyclopropane ring formation mechanism.55...

In related syntheses of aminocyclopropylcarboxylic acids and acid derivatives, different combinations of protecting groups have been employed and among the compounds made were carnosadine (8), ( + )-2,3-methano-5-oxoproline (9), ( + )-2,3-methanoproline (10), /rani-l-benzoylamino-2-phenylcyclopropane-l-carboxylic acid (11) (and variants with substituted phenyl and thiophene) tra i-l-amino-2-isopropylcyclopropane-l-carboxylic acid (12) and coronamic acid (13). ... 

The Jorgensen sector rule was successfully applied to the determination of the absolute configuration of d- and L-coronamic acid (5) (Ichiara et a/.. 

Coronamic acid, Coronafacic acid see coronatine. Coronarldine see iboga alkaloids. 

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