1-Aminocyclopropane carboxylic acid derivatives

In this last section the preparation of aminocyclopropane carboxylic acid derivatives by nitrogen extrusion from cyclic azoalkanes will be discussed. These amino... 

Photochemical Fe(CO)5-induced rearrangement of silylated allyl amine 9 gave N-silylated enamine 1015, which on subsequent Cu-catalyzed cyclopropanation by methyl diazoacetate afforded cyclopropane derivative 11. The use of an optically active catalyst gave an asymmetric induction of 56% ee for the cis isomer and 20% ee for the trans isomer. Further acid-induced ring cleavage afforded the -formyl ester 12, whereas reduction and desilylation produced aminocyclopropane carboxylic acid 13 (equation 2). 

The acyl azide - isocyanate rearrangement is known to proceed stereospecifically with retention of both optical and geometrical (cis-tranSy endo-exo) configuration. Thus, optically active aminocyclopropanes were obtained from optically active cyclopropane carboxylic acid derivatives A lot of exo-amiobicyclo[n.l.O]alkanes or... 

It is not intended to list here all aminocyclopropane compounds with pharmacological or biochemical effects nor to mention the numerous papers dealing with investigations of the most outstanding aminocyclopropane derivatives such as tranylcypromine (see Section III.B.2) or aminocyclopropane carboxylic acid (see Section III.B.3). Biochemical aspects of aminocyclopropane derivatives are part of Chapter 16, which gives more comprehensive information. 

Aminocyclopropane- -carboxylic Acid. The acetyl derivative (170 mg) in H2O (2mL) and coned HCl (1 mL) was heated under reflux for 4 h. The mixture was evaporated to dryness under vacuum, the crystalline residue dissolved in H2O, and passed down an anion exchange column (IR-4B, 10 g, 20-50 mesh). Evaporation of the eluate in vacuo gave 1-aminocyclopropane-l-carboxylic acid as colorless crystals yield 87 mg (73%) mp 299-231 °C (HjO/EtOH). 

The second chirality source used in the synthesis of aminocyclopropane carboxylic acids was D-glyceraldehyde acetonide, which after Wittig-Homer-Emmons reaction provided the alkenes 61. Treatment with diazomethane and subsequent irradiation at low temperatures alforded the cyclopropanes 62, which were converted into several other derivatives by modification of the side chain (Scheme 11). Notably, the best results were obtained by irradiating in the presence of benzophenone as triplet sensitizer [33, 34]. Following a similar synthetic procedure allocoronamic acid 65 was prepared, which is one of the amino acids that can be processed by plant tissues and promises the possibility to control the enzymatic processes underlying plant growth and fruit ripening [35]. 

Furthermore, selective monoarylation of 1-aminocyclopropane-l-carboxylic acid derivative 83 was achieved in the presence of alkoxy-substituted quinoline 85 in good yield (Scheme 23) [45]. Only one diastereomer of the unnatural amino acid derivative 84 was produced. 

L-Methionine, (S)- -amino-y-methylthiobutyric acid, is one of the most important sulfur-containing primary amino acids. Secondary products derived from L-methionine either contain still the more or less complete methionine skeleton [cf. the formulas of S-adenosyl-L-methionine, azetidine-2-carboxylic acid, 1-aminocyclopropane carboxylic acid (Fig. 192), spermidine and spermine (Fig. 193)], or only the methyl group of L-methionine (most 0-, iV-, S- and C-methylated secondary products). The sulfur-containing derivatives possess either a sulfide (—S—) or a sulfonium (—S+—) group. 

Interestingly, cyclopropanone hemiacetals provide a rapid way to prepare a-aminocyclopropane-carboxylic acids (ACCs) and phosphonic acids analogues (ACPs). Thus, asymmetric Strecker reaction of hemiacetal with an amine in acidic sodium cyanide selectively affords ci5 -a-aminocyclopropane-carbonitriles, precursors of ACC amino acid derivatives (eq 24). ... 

The possibility that many organic compounds could potentially be precursors of ethylene was raised, but direct evidence that in apple fruit tissue ethylene derives only from carbons of methionine was provided by Lieberman and was confirmed for other plant species. The pathway of ethylene biosynthesis has been well characterized during the last three decades. The major breakthrough came from the work of Yang and Hoffman, who established 5-adenosyl-L-methionine (SAM) as the precursor of ethylene in higher plants. The key enzyme in ethylene biosynthesis 1-aminocyclopropane-l-carboxylate synthase (S-adenosyl-L-methionine methylthioadenosine lyase, EC 4.4.1.14 ACS) catalyzes the conversion of SAM to 1-aminocyclopropane-l-carboxylic acid (ACC) and then ACC is converted to ethylene by 1-aminocyclopropane-l-carboxylate oxidase (ACO) (Scheme 1). 

A similar 3-(2-bromoethyl) derivative has been utilized to synthesize 1-aminocyclopropane-1 -carboxylic acid by an intramolecular base-catalyzed cyclization. This was possible when position 6 was blocked by the presence of two substituents. Some unexpected stereochemical results also came up in this study (85MI2). The starting material was the piperazine-2,5-dione derived from (/ )-(+ )-2-methyl-3-phenylalanine and glycine. The bislactim ether derived from this, on treatment with butyl lithium in THF at -78°C, gave the lithio derivative. Alkylation of this with 2-haloethyl... 

A few natural products which contain the cyclopropyl ring have been synthesized through metal catalysed cyclopropanation using dicarbonyl diazomethanes. ( )-Cycloeudesmol 63, isolated from marine alga Chondria oppositiclada, was synthesized via a sequence involving a copper catalysed cyclopropanation of a-diazo-/8-ketoester 61 to give the key intermediate 62 (equation 73)1 7,108. Similarly, the bicyclo[3.1.0]hexane derivative 65 was synthesized from the corresponding a-diazo-/8-ketoester 64 via the catalytic method and was converted into ( )-trinoranastreptene 66 (equation 74)109. Intramolecular cyclopropanation of -diazo-/i-ketoesters 67 results in lactones 68 which are precursors to 1-aminocyclopropane-l-carboxylic acids 69 (equation 75)110. 

In this section we analyze information about metabolic cleavage or breakdown of cyclopropane rings in three instances the biosynthesis of irregular monoterpenes, the ringopening of cycloartenol (20) derivatives, and the metabolic opening of 1-aminocyclopropane-1-carboxylic acid (ACPC) (9) by two quite distinct fragmentation routes. We will not explicitly discuss the processing of presqualene pyrophosphate (77) and prephytoene pyrophosphate (89) to squalene (76) and phytoene (88) respectively, since those transformations have already been dealt with in Section II. 

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. 

Aminocyclopropane-1-carboxylic acids. These cyclopropyl amino acids can be obtained in high chemical and optical yield by reaction of this ylide with the a, /3-dehydro lactones (3) prepared from (5S,6R)-4-/-butoxycarbonyl-5,6-diphenyl-2,3,5,6-tctrahydro-4W-l,4-oxazin-2-one (2, 14,58-59). The reaction of 3 with the ylide derived from... 

Even more convoluted are the structures of the indolic spiroindimicins, e.g., A (49) and D (50) from a deep-sea-derived Streptomyces sp. though the two tryptophan residues (one colored red (gray in print versions)) can be clearly discerned (2012OL3364). A tryptophan unit is also visible in the structure of cottoquinazoline D (51), isolated from a coral-associated fungus Aspergillus versicolor (20110L1130). This structure also includes a 1-aminocyclopropane-l-carboxylic acid residue. 

Microorganisms and plants can synthesize many uncommon amino acids. For example, some microbes make 2-aminoisobutyric acid and lanthionine, which is a sulfide-bridged derivative of alanine. Both of these amino acids are found in peptidic lantibiotics such as alamethicin. While in plants, 1-aminocyclopropane-l-carboxylic acid is a small disubstituted cyclic amino acid that is a key intermediate in the production of the plant hormone ethylene. 

A common neutral amino acid derived from cyclopropane is 1-aminocyclopropane-l-carboxylic acid. The precursor of this carboxylic acid is methionine, or strictly S-adenosyl-L-methionine which is derived from methionine (Figure 2.1). 1-Aminocyclopropane-l-carboxylic acid is also present in apples, pears and other fruits. 1-Aminocyclopropane-l-carboxylic acid serves as a precursor of ethylene (ethene) in essentially all tissues of... 

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