Aspartate/aspartic acid synthesis

S. Roweton, S. Huang, G. Swift, Poly (aspartic acid) synthesis, biodegradation, and current applications, J. Environ. Polym. Degradation 5 (1997) 175-181. 

Polaczek J, Pielichowski J, Pielichowski K et al (2005) A new method of poly(aspartic acid) synthesis under microwave radiation. Polimery 50 812-820... 

Aspartame (L-aspartyl-L-phenylalanine methyl ester [22839-47-0]) is about 200 times sweeter than sucrose. The Acceptable Daily Intake (ADI) has been estabUshed by JECFA as 40 mg/kg/day. Stmcture-taste relationship of peptides has been reviewed (223). Demand for L-phenylalanine and L-aspartic acid as the raw materials for the synthesis of aspartame has been increasing, d-Alanine is one component of a sweetener "Ahtame" (224). 

The carboxamidomethyl ester was prepared for use in peptide synthesis. It is formed from the cesium salt of an A-protected amino acid and a-chloroacetamide (60-85% yield). It is cleaved with 0.5 M NaOH or NaHCOa in DMF/H2O. It is stable to the conditions required to remove BOC, Cbz, Fmoc, and r-butyl esters. It cannot be selectively cleaved in the presence of a benzyl ester of aspartic acid. ... 

Dimethyl-3-pentanoL DCC, DMAP, CH2CI2, 4 h. This group was developed as an improvement over the use of cylcohexanol for aspartic acid protection during peptide synthesis. ... 

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

Arrhenius, Svante, 86,353 Arsenic, 573-574 Asparagine, 622t Aspartic acid, 622t Aspirin. See Acetylsalicylic acid Astaxanthin, 157 Asymmetric synthesis, 601 Atherosclerosis, 604... 

Merck s thienamycin synthesis commences with mono (V-silylation of dibenzyl aspartate (13, Scheme 2), the bis(benzyl) ester of aspartic acid (12). Thus, treatment of a cooled (0°C) solution of 13 in ether with trimethylsilyl chloride and triethylamine, followed by filtration to remove the triethylamine hydrochloride by-product, provides 11. When 11 is exposed to the action of one equivalent of tm-butylmagnesium chloride, the active hydrogen attached to nitrogen is removed, and the resultant anion spontaneously condenses with the electrophilic ester carbonyl four atoms away. After hydrolysis of the reaction mixture with 2 n HC1 saturated with ammonium chloride, enantiomerically pure azetidinone ester 10 is formed in 65-70% yield from 13. Although it is conceivable that... 

The noteworthy successes of a relevant model study12 provided the foundation for Merck s thienamycin syntheses. In the first approach (see Schemes 2 and 3), the journey to the natural product commences from a readily available derivative of aspartic acid this route furnishes thienamycin in its naturally occurring enantiomeric form, and is noted for its convergency. During the course of this elegant synthesis, an equally impressive path to thienamycin was under parallel development (see Schemes 4 and 5). This operationally simple route is very efficient (>10% overall yield), and is well suited for the production of racemic thienamycin on a commercial scale.. x... 

Alpert has shown [47] that poly(succinimide)-silica can be further hydrolyzed to poly (aspartic acid)-silica or condensed with [3-alanine in aqueous solution to form a covalently bonded copolymer of 2-carboxyethyl aspartamide and aspartic acid. The content of carboxyl groups generated by this way has not been quantified directly, but the cation-exchange hemoglobin capacity has been measured for a series of the packings. Thus, the optimal concentration of poly(succinimide) used in the synthesis was found to be 2 5%. 

THE USE OF POLYSTYRYLSULFONYL CHLORIDE RESIN AS A SOLID SUPPORTED CONDENSATION REAGENT FOR THE FORMATION OF ESTERS SYNTHESIS OF N-[(9-FLUORENYLMETHOXY)CARBONYL]-L-ASPARTIC ACID a tert-BUTYL ESTER, P (2-ETHYL[(lE)-(4-NITROPHENYL)AZO] PHENYL]AMINO]ETHYL ESTER... 

A synthesis of aspartic acid is based on this strategy. Disconnection (a) is attractive since acyl-amino malonate (7) is a reagent for synthon (6). Synthon (8) can be represented by allyl bromide. 

In the published synthesis the ozonolysis is performed on the protected product (9) and aldehyde (10) isolated before oxidation, hydrolysis and decarboxylation give aspartic acid. 

Another competing cyclisation during peptide synthesis is the formation of aspartimides from aspartic acid residues [15]. This problem is common with the aspartic acid-glycine sequence in the peptide backbone and can take place under both acidic and basic conditions (Fig. 9). In the acid-catalysed aspartimide formation, subsequent hydrolysis of the imide-containing peptide leads to a mixture of the desired peptide and a (3-peptide. The side-chain carboxyl group of this (3-peptide will become a part of the new peptide backbone. In the base-catalysed aspartimide formation, the presence of piperidine used during Fmoc group deprotection results in the formation of peptide piperidines. 

Reider, P.J. Sc Grabowski, E.J.J. (1982) Total Synthesis of Thienamycin A New Approach from Aspartic Acid. Tetrahedron Letters, 23, 2293-2296. 

L-Asparaginase is an enzyme that may be produced by Escherichia coli. Asparaginase hydrolyzes the reaction of asparagines to aspartic acid and ammonia to deplete lymphoid cells of asparagine, which inhibits protein synthesis. The... 

The molar ellipticity of these dendrimers was found to increase proportional to the number of chiral end groups. This is to be expected, in the absence of interactions between the terminal tryptophane moieties. No higher-generation dendrimers of this type have been reported. Other amino-acid-containing chiral dendrimers have been described by Meijer et al. who attached various amino acid derivatives to the periphery of poly(propylene imine) dendrimers (see Sect. 3) and more recently by Liskamp et al. (modification of polyamide dendra) [22] and Ritter et al. (synthesis of grafted polymerizable dendrimers containing L-aspartic acid components) [23]. 

Figure 4.16 Pressurized fixed-bed reactor synthesis of L-aspartic acid from fumarate applying a plug flow reactor followed by a crystallization step for downstream processing...

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