Phenyl-propionic Acids

To a solution of (R/ ,SS)-2-methyl-3-phenyldimethylsilyl-3-phenyl-propionic acid (50 mmol) (see Chapter 8) in dichloromethane (50 ml),... 

Fig. 7. Effect of modifying pH on EDA of MRNi (O) (S)-manderic acid MRNi (33) ( ) (S)-2-hydroxy-3-phenyl-propionic acid-MRNi (33) ( ) (S)-aspartic acid-MRNi (19) (A) (R.R),tartaric acid-MRNi (25). Modifying conditions 0°C. Reaction conditions MAA (neat), 60 C, 80-100 kg/cm2.

Bromination of cinnamic acid with NBS in aq. MeOH gives 2-bromo-3-methoxy-3-phenyl propionic acid, PhCH(0Me)CHBrC02H. At moderately high [H+] the reaction is second-order and independent of [H+], whereas at low [H+] the rate increases with decrease in [H+], Succinimide inhibits the reaction182. 

FIGURE 4.5 Chromatograms of (a-e) tetralone derivatives on ristocetin A CSP using hexane-ethanol-TEA (12 8 02, v/v/v), (f) 3-amino-3-phenyl propionic acid [methanol-water (60 40, v/v)], (g) midodrine [methanol-1% triethyl ammonium acetate buffer, pH 7 (20 80, v/v)], (h) A-FMOC-glycy 1-arginine [methanol-water (60 40, v/v)], (i) thyroxine [methanol-1% triethyl ammonium acetate buffer, pH 7 (20 80, v/v)], (j) trihexyphenidyl [methanol-1% triethyl ammonium acetate buffer, pH 7 (20 80, v/v)] and (k) verapamil [methanol-1% triethyl ammonium acetate buffer, pH 7 (20 80, v/v)] on avoparcin CSP (From Refs. 8 and 14.)... 

Finally, stereochemical or simply chemical considerations have led several authors to postulate the formation of a p-lactone whenever they have had to deal with a reaction involving ammonia or an amine in aqueous or alooholic solution and a P-halo aoid. Some of the older literature on this subject has been discussed by Darapsky and others, > notably the formation of 3-phenylhydracrylamidu by t-hc reaction of ammoDium hydxosidc with 3-bromo-3-phenyl-propionic acid ... 

Low-temperature reaction of diethyl 1-oxopropylphosphonate with LiHMDS affords exclusively the (Z)-enolate, which, on condensation with benzaldehyde in excess (2.2 eq), gives a highly diastereoselective reaction leading to the formation of syn- and anZz-3-hydroxy-2-methyl-3-phenyl-propionic acids in a 97% yield, together with diethyl 1-hydroxy benzyl phosphonate. 

Scheme 66 Synthesis of 2-hetero-(benzisothiazol-3-yl)(3-phenyl)propionic acids...

Starting from 2-oxo acids, various optically pure (S)-amino acids can be quantitatively synthesized by using PheDII and formate dehydrogenase. Tabic 8 shows the yields of the (S)-amino acids thus synthesized. The reductive amination products derived from (3/ /,S )-3-methy 1-2-ox ovaierate and (37 /5)-3-methyl-2-oxo-3-phenylpyruvate have been identified as diastereomeric mixtures of (S)-isoleucine and (S)-alloisoleucine, and (2S,3f / S)-2-amino-3-methyl-3-phenyl-propionic acid, respectively. The product from 2-oxo-5-phcnylvalerate solidified as the reaction proceeded. 

The A log Ka for similar substitutions in saturated acids are hardly significant, being +.01 and +.06 respectively. The slopes of the cinnamic and /3-phenyl propionic acid lines in Figure 36 also illustrate this point. 

FIGURE 16.10 Preparation of the chiral C-13 paclitaxel side-chain synthon. (A) Enantio-selective microbial reduction of 2-keto-3-(Al-benzoylamino)-3-phenyl propionic acid ethyl ester 36. (B) Enantioselective enzymatic hydrolysis of cw-3-(acetyloxy)-4-phenyl-2-azetid-inone 38. 

Patel RN, Banerjee A, Howell JM, McNamee CG, Brzozowski D, Nanduri V, Thottathil JK, Szarka LJ (1995) Stereoselective Microbial Reduction of 2-Keto-3-(N-benzoylamino)-3-phenyl Propionic Acid Ethyl Ester Synthesis of Taxol Side-Chain Synthon. Ann NY Acad Sci 750 166... 

Eligh yields of esters are obtained from both acid-sensitive (cyanoacetic acid) and base-sensitive carboxylic acids (3-phenyl-propionic acid and trichloroacetic acid) and, in these latter cases, use of 4-(dimethylamino)pyridinium chlorosulfite chloride is much more effective than use of thionyl chloride alone. The esterification process has been claimed to be independent of the steric environment of the carboxyl function, though this reagent may be of more limited value with heavily substituted benzoic acids. Carboxyl activation, in the presence of a primary amine, leads to the corresponding amide in excellent yield (eq 2). In both the esterification and amidation processes and the oxime dehydration reaction discussed below, recovery of DMAP is straightforward. 

C11H14O2 3-phenyl-propionic acid ethyl ester 2021-28-5... 

C18H28O2 3-phenyl-propionic acid 3,5,5-trimethyl-hexyl ester ... 

C21H34O2 3-phenyl-propionic acid dodecyl ester 112715-88-5... 

Thus, compounds 5 and 6, two lead molecules within the class of hPPAR 2-aryloxy-3-phenyl propionic acid agonists, exhibit opposite enantiopreference for compound 1, the main object of our consideration in this chapter, which is also an 2-aryloxy-propionic acid derivative. Since, no details of the structure of the complex of 1 and the LBD of hPPARs were reported, it can be assumed that the absence of a phenyl group at position C(3) in 1 somehow results in inverse steric requirements for this agonist at LBD, when compared with its 3-phenyl congeners, 5 and 6. Since, the route to enantiomerically pure (R)-l includes a number of original synthetic solutions, a detailed discussion of these is presented in later sections. 

I, (25,35) ( )3-omino-2-hydroxy - 3-phenyl propionic acid (phenyhBo serine)... 

A good yield (70%) of /3-phenylethylamine is obtained from /3-phenyl-propionic acid, but the introduction of methoxyl groups in the benzene ring causes a sharp drop in the yields of the amines. ... 

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