Aspartic acid derivative

In a comparable approach, Roques and coworkers [15] converted the aspartic acid derivative 7-23, which bears a protected thiol in the 3-position, into unsaturated compounds 7-27 and 7-28, respectively (Scheme 7.9). 

The phosphoramidite ligands that are the focus of the remainder of this chapter have prompted the investigation of ligands containing related structures. Iridium complexes of aspartic acid-derived P-chirogenic diaminophosphine oxides (DlAPHOXs) catalyze the amination [62] and alkylation [63] of aUyhc carbonates (Scheme 6). With BSA as base and catalytic amounts of NaPFs as additive, branched amination and alkylation products were obtained from cinnamyl carbonates in excellent yields and enantioselectivities. However, the yields and enantios-electivities were lower for the reactions of alkyl-substituted aUyhc carbonates. Added LiOAc increased the enantioselectivities of aUyhc alkylation products. 

Scheme 2.63 The conversion of a-tert-butyl aspartic acid derivatives to the corresponding acyloxyketone.

The double bond of 2,2-bis(trifluoromethyl)-5(2f/)-oxazolone 71 reacts with ynamines and the resulting cycloadduct 81 is converted into the corresponding amino acid after hydrolysis. The procedure constitutes a new route to 3-alkyl-substituted aspartic acid derivatives 83 (Scheme 7.20 Table 7.14, Fig. 7.15). 

TABLE 7.14. 3-ALKYL ASPARTIC ACID DERIVATIVES EROM REACTION OF 5(277)-OXAZOLONES WITH YNAMINES"... 

TABLE 7.14 3-ALKYL ASPARTIC ACID DERIVATIVES FROM REACTION OF 5(2//)-OXAZOLONES WITH YNAME/ES, 149... 

Table 5. Enantioselective Alkylation of (S)-Aspartic Acid Derivatives (181a, b)...

To a solution of 86 (1.25 g, 1.65 mmol) in dry acetonitrile (30 mL) were added the aspartic acid derivative 87 (652 mg, 1.83 mmol) and AF-bromosuccinimide (444 mg, 2.50 mmol). The mixture was stirred in the dark at room temperature under argon. After 1 h, aqueous NajSjOj (10 mL) was added, the bulk of organic solvent was evaporated under reduced pressure, and the residue was partitioned between water (100 mL) and chloroform (100 mL). The aqueous layer was extracted with chloroform (3 x 100 mL). The combined organic layers were washed with water (2 x 75 mL) and dried, and the solvent was removed under reduced pressure. Flash column chromatography (light petroleum-ethyl acetate, 4 1)... 

In this section we provide experimental procedures for the synthesis of various 2-nitrophenyl-containing amino acid derivatives glutamic acid derivative 109 230 (Scheme 28), glycine derivative 112 230 and aspartic acid derivative 114 230 (Scheme 29), Fmoc-protected tyrosine derivative 119 234 (Scheme 30), and glycine derivatives 120 235 and 122 232 (Scheme 31). 

Most traditional methods use hydrochloric acid solutions as the acid reagent for the hydrolysis or alcoholysis of fi-lactams. Methanolic solutions of trimethylchloro-silane are able to generate HCI in situ, and the trick has been employed successfully for the methanolysis of fi-lactams in a route to aspartic acid derivatives [60, 61] and 2-oxazolidinones[62], respectively. Recently the use of silica-supported acid reagent has been reported as a convenient alternative. The reagent (Si02-Cl) prepared from admixing silica gel and SOCl2 in dichloromethane and subjected to dryness, is able to run the methanolysis of (1-lactams at room temperature in 20 min [63]. 

From the ring opening of p-lactams by amines and a-amino acids, p-amino amides and fi-amino acid derived peptides are generated. These structures are of interest because of their presence in several naturally occurring macrocyclic compounds [82, 83]. One example of the latter is the p-hydroxy aspartic acid derived tripeptide 45 found in the macrocyclic peptide lactone antibiotic lysobactin 40 [84], Fig. 4. 

Synthesis of Conformationally Constrained a-Substituted Serine and Aspartic Acid Derivatives... 

Samarium iodobinaphtholate (222) has been reported to act as an efficient enantioselective catalyst for the Michael addition of aromatic amines to fumaryl oxazolidinone (220), affording the aspartic acid derivatives (221) in good yields. Elucidation of the influence of temperature on the addition of p-anisidine revealed an isoinversion effect with a maximum ee of 88% at —40 °C.257 A non-enantioselective version of this reaction has also been reported.258... 

Scheme 1. Synthesis of aspartame using an activated TV-protected aspartic acid derivative.

Fig. 13. Synthesis of (3-linked asparagines glycosides (a) dicyclohexylcarbodiimide (DCC) and l-hydroxybenzotriazole(HOBt) coupling (98), (b) pentafluorophenyl (OPfp) ester of aspartic acid derivative coupling (97).

Formation of an amide bond between a glycosyl amine and aspartic acid derivative or an aspartic acid-containing peptide can be than achieved by methods used for the formation of a peptide bond (Fig. 13) (40,97-99). 

Preparation of an aspartic acid-derived organozinc iodide in DMF, and its coupling with iodobenzene... 

Preparation of cyclic compounds via 5-exo-trig or 6-exo-trig manner with O-acyl esters (2) proceeds effectively [36-40]. Eq. 8.13 shows the preparation of biologically active perhydroindole-2-carboxylic acids (22a) and (22b) from an aspartic acid derivative via 5-exo-trig manner. 

The last of these special examples of SN reactions of heteroatom nucleophiles at the carboxyl carbon of a carboxylic acid derivative is given in Figure 6.21. There, the free carboxyl group of the aspartic acid derivative A is activated according to the in situ procedure of Figure 6.14 as a mixed carbonic acid/carboxylic acid anhydride B that is then treated with N,0-dimethylhydroxyl amine. This reagent is an N nucleophile, which is thus acylated to give the... 

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