Monatin

Synthesis of (—)-monatin (524), a high-intensity sweetening agent, was achieved by chelation-controlled cycloaddition of chiral oxazinone-derived nitrone (16 ) to allyl alcohol (520) in the presence of MgBr2 OEt2 (Scheme 2.248) (746). 

Y. Amino K. Yuzawa K. Mori T. Takemoto, Crystals of Non-Natural Stereoisomer Salt of Monatin as Sweeteners. PCT Int. Appl. WO 2003045914, 5 June 2003. 

Several examples have been reported also this year, and among them there are the total syntheses of the natural products (-i-)-hyacinthacine A2 (73) <03TL2315> (for an analogous approach to 73 see <03SL35>), (-)-monatin 77 <03CC2678>, and (-i-)-heliotridine 81 <03EJO4373>. In all these cases, the reductive opening of the N-0 bond of cycloadducts 75, 79, and 83 was followed by a spontaneous cyclization to afford y-lactam 74, y-lactone 78, and pyrrolizidine 82, respectively. 

A highly sweet amino acid, monatin (83), was isolated from an African plant, Schlerochiton ilicifolius A. Meeuse (Acanthaceae) [101]. Monatin (83) was rated as being comparable to the synthetic amino acid, 6-chloro-D-tr3T>tophan, which showed a sweetness intensity of 1,300 times that of sucrose. Monatin (83) appears to be the only native plant amino acid with a highly sweet taste to have been discovered. 

FIGURE 1 Molecular formulas of some sweet molecules, representative of the major natural classes carbohydrates (sucrose), polyols (glycerol, sorbitol), amino acids (glycine, tryptophan), peptides (aspartame, monatin). 

Bassoli, A., Borgonovo, G., Busnelli, G., Morini, G., and Merlini, L. (2005). Monatin, its stereoisomers and derivatives, modeling the sweet taste chemoreception mechanism. Eur. J. Org. Chem. 2005, 2518-2525. 

The sensory data for the sweet plant-derived compounds in Table I refer to sweetness intensity comparisons with sucrose on a weight basis. However, comparison of these data is most reliable for compounds in the same structural class that have been evaluated for sweetness intensity in the same laboratory. Also, sweetness intensity values tend to vary depending upon concentration of the tastant compound. For example, the sodium salt of the newly discovered amino acid, monatin (69) exhibited relative sweetness intensities to 5% and 10% w/v sucrose of 1,400 and 1,200, respectively (73). Therefore, for this compound, and for several others listed in Table I, sweetness intensity values are expressed as ranges. 

Monatin, 4-hydroxy-4-(indoT3-ylmethyl) glutamic acid, a high-intensity sweet, natural compound. Monatin was isolated from the roots of Schlerochiton ilicifolius, a spinyleaved hardwood shrub growing in South Africa. The synthesis of the four... 

Monatin [(25,45)-4-hydroxy-4-(indol-3-ylmethyl)-L-glutamic acid],... 

Fry JC, Yurttas N, Biermann KL, Lindley MG and Goulson MJ. (2012) The sweetness concentration-response of r,r-monatin, a naturally occurring high-potency sweetener. 

A pyruvate aldolase from Pseudomonas taetrolens catalyzes the aldol addition of pyru-vafe to indole-pyruvic acid (34), a ketone [85]. This is an interesting example of an aldolase fhaf cafalyzes an aldol addition to a ketone acceptor. A variant of this aldolase was used in fhe stereoselective synfhesis of a precursor (35) of monatin (36), whose 2R,4R stereoisomer is 2700-fold sweeter fhan sucrose (Scheme 10.3) [86]. 

Enzymatic synthesis of a precursor of monatin (36) using pyruvate-dependent aidoiases from Pseudomonas taetrolens (PyAp... 

The 4-hydroxy-4-substituted glutamic acid moiety is the common substructure (stmcture 60) of several unusual, naturally occurring, biologically important amino acids such as monatin (61) [31] (high intensity sweetener), lyco-perdic acid (62) [32], and dysiherbaine (63) [33] (agonist of... 

In 1992, monatin [(25,45)-61], a 4-hydroxy,4-substituted glutamic acid, was isolated from the bark of the roots of Schlerochiton ilicifolius and reported to be 1000 to 1400 times sweeter than sucrose [31]. However, the natural supply of (25, 45)-61 from dried bark was insufficient for further... 

To demonstrate the synthetic utility of the cycloaddition of nitrone (S)-29 with alkene 78, synthesis of the (25,4/ )-monatin (80) from cycloadduct 79e was examined (Scheme 6.22). Thus, hydrogenolysis of 79e by using Perlman s catalyst gave a lactone, which, on treatment with LiOH in MeOH-H20 at room temperature, underwent hydrolysis to give 80 without isomerization in 33% yield. 

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