Penicillamine cyclic

A successful synthesis (Scheme 19) of the phosphonic acid analogues of D-and L-penicillamine commences with the cyclic phosphorochloridite (132). Other attempts using (132 ... 

Wangfuengkanagul and Chailapakul [9] described the electroanalysis of ( -penicillamine at a boron-doped diamond thin film (BDD) electrode using cyclic voltammetry. The BDD electrode exhibited a well-resolved and irreversible oxidation voltammogram, and provided a linear dynamic range from 0.5 to 10 mM with a detection limit of 25 pM in voltammetric measurement. In addition, penicillamine has been studied by hydrodynamic voltammetry and flow injection analysis with amperometric detection using the BDD electrode. 

Hoppe, I., Schollkopf, U., Nieger, M., and Egert, E., Asymmetric addition of a chiral cyclic phosphite to a cyclic imine — synthesis of phosphonic acid analogues of d- and L-penicillamine, Angew. Chem., Int. Ed. Engl., 24, 1067, 1985. 

Mosberg, H.I., Hurst, R., Hruby, V.J., Gee, K., Akiyama. K., Yamamura, H.I., Galligan, J.J., Burks, T.F. Cyclic penicillamine containing enkephalin analogs display profound delta receptor selectivities, Life Sci 1983, 33 Suppl. 1, 447-50. 

A woman with Wilson s disease treated with penicillamine developed severe hirsutism (257). After treatment with oral contraceptives, her breasts enlarged rapidly, and she had cyclic mastodynia. Around the same time she also developed gingival hyperplasia. 

Similarly, 2,3-dihydro-5-oxo-thiazolo[3,2-a]pyridine-3,7-dicarboxylic acids are formed in the reaction between a-amino-/3-mercaptocarboxylic acids with citric acid. In the reaction of (S)-penicillamine the cyclic product (501) was reported to be racemized (71T3447). 

The two most common reactions for the generation of cyclic peptides are (i) disulfide formation between cysteine or penicillamine residues through oxidation, and (ii) lactam formation between the amino and carboxy terminal ends (head-to-taU cyclization), the annino terminus and the side chain of an aspartic or glutanoic add residue, or between the side chains of a lysine (or another diamino acid) and aspartic or glutanoic acid residues. A special mode of the second type is backbone cyclization between an amino group (N-terminal or side chain) and a carboxyalkylated backbone nitrogen. Both reactions have been used to generate cyclic peptide libraries. 

In a 25-year-old woman with Wilson s disease, treatment with penicillamine (1.5 g/day) was first followed by the development of hirsutism, mainly of the face (255). After she started to use an oral contraceptive, her breasts enlarged rapidly and she experienced cyclic mastodynia in addition, gingival hyperplasia developed. All symptoms improved on withdrawal of penicillamine, but additional mammoplasty was needed. 

Tetramethyl-3-thiazoline was used as a model compound to study the hydrophosphonylation of cyclic imines for the production of pharmaceutically interesting a-amino phosphonates (eq. (19)) [172]. The resulting thiazolidinyl-phosphonate can be regarded as an lV,S-protected phosphonic acid analogue of the a-amino acid D-penicillamine which functions, e. g., as an HIV-protease inhibitor. 

Various peptides from the enkephalin family, or analogs of these molecules, permeate through the blood-brain barrier at different rates, often by different mechanisms [49]. For example, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (a cyclic peptide that binds to jU.-opioid receptors, in which Pen is penicillamine) permeates by diffusion only Tyr-D-Pen-Gly-Phe-D-Pen ([d-Penj -enkephalin, a cyclic Met-enkephalin analog that binds to 5-opioid receptors) permeates by diffusion and a saturable transport mechanism (Tyr-D-Ala-Gly-Phe-NH)2 (biphalin, a dimeric analog that is active at fx-... 

The description of diorganotin complexes with penicillamine enantiomers and 3-thiopropanoic add in the solid state was undertaken. The 3-thiopropanoic acid complexes derivatives contain both trigonal bipyramidal and tetrahedral structures about the tin. These structures are maintained initially after solution. Again, cyclic formation with chelation occurring with the carbonyl oxygen of the carboxylic group occurs [66]. 

Other catalysts besides proline have also been investigated. A particularly large amount of data has been collected for the aldol reaction of acetone tvith p-nitrobenzaldehyde (Scheme 4.32). Simple primary a-amino acids and acyclic N-methylated a-amino acids are not catalytically active under standard reaction conditions. Of the simple cyclic amino acids studied, azeti-dine, pyrrolidine, and piperidine 2-carboxylate, proline is clearly the best catalyst, a-, a -, and, in particular, N-methylation reduce the efficiency and vhereas substitution of the 3- and 4-positions are tolerated vithout dramatic effects. Proline amide is essentially catalytically inactive under the standard reaction conditions (DMSO, room temperature, 2 h) but after three days, the aldol could be isolated in good yields, albeit vith very low enantiose-lectivity. Clearly, the carboxylic acid plays an important role in the catalysis and in determining enantioselectivity. That the enantioselectivity can be improved vas sho vn vith penicillamine derivative 168, proline derived diamine salt 169, and amide 170 [129-132]. 

Schlauch M, Frahm AW. A thermodynamic study of the temperature-dependent elution order of cyclic a-amino acids on a copper (II)-D-penicillamine chiral stationary phase. Anal. Chem. 2001 73 262-266. 

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