Proline, 3,4-dehydro

In contrast to proline, 3,4-dehydro-DL-proline (167) does not give a color with isatin.469 The reaction proceeds to give 168 and the mechanism of formation has been discussed.469 Both cis- and react with isatin to give 168. A... 

However, excellent optical yields have been obtained for the hydrogenation of cyclodipeptides. As early as 1944, M. Bergmann and J. E. Tietzmann 84m) obtained the diketopiperazine of (S)-phenylalanyl-(S)-proline (49), while hydrogenating dehydro-phenylalanyl-(S)-proline diketopiperazine (48). 

Isolation of alkaline phosphatase from Escherichia coli in which 85% of the proline residues were replaced by 3,4-dehydro-proline affected the heat lability and ultraviolet spectrum of the protein but the important criteria of catalytic function such as the and were unaltered (12). Massive replacement of methionine by selenomethionine in the 0-galactosidase of E. coli also failed to influence the catalytic activity. Canavanine facilely replaced arginine in the alkaline phosphatase of this bacterium at least 13 and perhaps 20 to 22 arginyl residues were substituted. This replacement by canavanine caused subunit accumulation since the altered subunits did not dimerize to yield the active enzyme (21). Nevertheless, these workers stated "There was also formed, however, a significant amount of enzymatically active protein in which most arginine residues had been replaced by canavanine." An earlier study in which either 7-azatryptophan or tryptazan replaced tryptophan resulted in active protein comparable to the native enzyme (14). 

A lipophilic tripeptide, janolusimide (342), was isolated from the Mediterranean nudibranch Janolus cristatus and was found to be toxic to mice (260). From the Swedish sponge Geodia baretti barettin, a cyclic polypeptide, was isolated and found to show inhibiting activity on electrically induced contractions of isolated guinea pig ileum (261). Barettin is composed of dehydro-6-bromotryptophan and proline. The initial proposed... 

Prior to the work of Holladay and co-workers,38 there was good literature precedent for 4-keto-L-proline derivatives 39 giving the required 3,4-dehydro isomer of the enamine rather than the 4,5-dehydro isomer in a report by Friary and co-workers.46 It was found that the protected 4-keto-L-proline derivative 49 gave enamine 50 on treatment with morpholine in the presence of molecular sieves (Scheme 17). 

Table 1 Selected adamantanyl derivatives and their corresponding mass spectral data. HPLC data supplied by the author. Cyclopropyl-fused dehydro pyrrolidines were prepared using (C2H5)2Zn, C1CH2I, and A-Boc-4,5-L-proline ester derivatives in CH2C12 according to the method of co-author Robl (1)...

Amino Acid Oxidase and Chemical In Situ Reduction of the Initially Formed Imino Compound A simple and interesting procedure for the deracemization of a-amino acids was introduced by Soda [48], who combined the oxidation of the D-enantiomer of D,L-proline to dehydro-prohne with a chemical reduction of the imine 21 in on -pot, thereby restoring the racemic mixture. If the reaction in the first step is completely enantioselective, the e.e. of the amino acid after one cycle is 50%. Repeating the reaction in successive cycles raises the e.e. close to 100% (Scheme 13.19). 

Assignment of configuration to the individual isomeric alcohols (60) and (61) has now been possible by high-field NMR, and confirmed by X-ray analysis [114]. In addition minor products from the borohydride reduction of pristinamycin 11 have been identified as the corresponding (R)- and (5)-proline derivatives of (60) and (61) which are produced as a result of reduction of the double bond of the dehydro-proline residue (see Sect. 5.4.5). 

In oxidized pristinamycin (80) the activated double bond of the dehydro-proline residue displayed the same reactivity towards thiols. Some water soluble derivatives of (80) were prepared by this route, but they were devoid of antibacterial activity. 

Iqbal and co-workers have described an interesting solvent and substituent dependent regioselective (5 n2 or Pd(0)-catalyzed synthesis of ot-dehydro-p-amino esters via treatment of the acetates of MBH adducts with amines (Scheme 3.118). For proline-based cyclic secondary amine and serine methyl ester, the corresponding ( )-allylamines 291 S-tfl ) were obtained exclusively in the presence of Pd(0) (catalyst) (Scheme 3.118). 

The stability of poly-L-proline form II helix can be enhanced by decreasing the rotational degree of freedom of the pyrrolidine ring, e.g., poly-3,4-dehydro-L-proline. 

Abbreviations used in this chapter AChR, acetylcholine receptor ANP, atrial natriuretic peptide ARIA, acetylcholine receptor-inducing activity AzC, L-azetidine CGRP, calcitonin gene related peptide 3,4 DHP, 3,4-dehydro-1-proline EDHB, ethyl-3,4-dihydroxybenzoate PCB, polychlorinated biphenyl. 

Other dehydro amino acids conveniently used in the same way include A " -proline and 2,6-diaminohex-3-ynoic acid (for [ H]lysine) °. These residues usually give more nearly stoichiometric tritium incorporation upon reduction than does A" -leucine. The tritiation of A -amino acids (or peptides containing them) would require stereoselective reductions in order to obtain the desired (R)- or (5)-forms (as discussed later in this section). 

The tunichrome Sp-1 is a pentapeptide that indudes two DOPAs, a glycine, a proline and a decarboxy-a,P-( )-dehydro-DOPA (dcADOPA). This derivative was extracted from the hemocytes of the stolidobranch ascidian Styela plicata, which is not known to accumulate vanadium, but the analogy with tunichromes seems obvious (Tincu and Taylor, 2002). 

K) A final route which cannot a priori be excluded as a possible biosynthetic pathway is the direct a-oxidation of amino acid derivatives to a-hydroxy-a-amino acid derivatives followed by elimination of water. In vitro oxidation of piperazinediones to a-hydroperoxides occurs very readily (cf. Section V.). The isolation of numerous dehydropiperazine-diones and corresponding mercaptopiperazinediones containing proline (or benzoproline , i. e. dihydroindole) units 341) necessitates the consideration of this route as a possible biosynthetic pathway. The hydroperoxypiperazinediones can readily be converted into dehydro-and mercaptopiperazinediones. 

Amides can be added to acylaminoacrylic ester even without acid catalysis to form the a,a-diacylaminopropionic acid ester 150, 364). An analogous addition has been described in the reaction of N-acyl-dehydro-proline with acetamide 136) (see Section IV. A. 6). Analogous intramolecular additions, leading to the formation of five- and six-membered rings, proceed even under basic catalysis (see Section VI. A. 2.4). 

Metabolite analogues. Azetidine-2-carboxylic acid (12.42) and 3,4-dehydro-DL-proline inhibit the growth of bacteria (and also of the seedlings of higher plants) by becoming incorporated into the protein in the place of proline (12.43) (Fowden, Neale, and Tristram, 1963). 

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