Ornithine esters

Houtsmuller, U. M. T., and L. L. M. van Deenen Identification of a bacterial phospholipid as an 0-ornithine ester of phosphatidyl glycerol. Biochim. biophys. Acta (Amst.) 70, 211 (1963). 

Houtsmuller and van Deenen (1963) reported that both phospholipase A and phospholipase C show activity towards the 0-ornithine ester of phosphatidyl glycerol. 

As this review is devoted to derivatives of amino acids and peptides linked to fatty acids by amide bonds, lipids containing ester-bound amino acids such as ornithine esters of phosphatidylglycerol (i) or lysine esters of diglycerides (2) will not be considered. 

S.P. solid-phase technique L.P. liquid-phase technique OPTcp pentachlorophenyl ester TEEP tetraethyl pyrophosphit OTCp trichlorophenyl ester ONp p-nitrophenyl ester ONSu N-hydroxysuccinimido ester OPFp pentafluorophenyl ester OQu 8-hydroxyquinyl ester OPy 3-hydroxy-pyridyl ester ODnp 2,4-dinitrophenyl ester DCC dicyclohexylcarbodiimide HOBn 3-hydroxy-4-oxo-3,4-dihydro-l,2,3-benzotriazin Opi JV-hy-droxypiperidine EEDQ 2-ethoxy-l-ethoxycarbonyl-l,2-dihydroquinoline Tos p-toluenesulfonyl PTC propanetricarboxylic acid OBu tm-butyl ester Nva norvaline Aha aminohexanoic acid Om ornithine... 

In view of this finding, it was proposed (135-138) (Scheme 22) that in the case of cocaine (98) the ornithine (201) is incorporated through free putrescine (202), which is a symmetrical intermediate and therefore would afford the pyrrolinium salt 206 equally labeled at C-2 and C-5. As above, condensation of the (V-methyl-A1 -pyrrolinium salt (206) with acetyl coenzyme A leads to the coenzyme A ester of hygrine-1 -carboxylic acid (207), which by transester-... 

The interaction with both synthetic and naturally occurring amino acids has been studied extensively glycine (138, 173, 219-221), a-(173, 219) and /3-alanine (138, 220), sarcosine (219), serine (222), aspartic acid (138, 173, 222-226), asparagine (222), threonine (222), proline (219), hydroxyproline (219), glutamic acid (138, 222-225), glutamine (222), valine (219, 227), norvaline (219), methionine (222, 226), histidine (228, 229), isoleucine (219), leucine (219, 230), norleu-cine (219), lysine (222), arginine (222), histidine methyl ester (228), phenylalanine (138, 222), tyrosine (222), 2-amino-3-(3,4-dihydroxy-phenyl jpropanoic acid (DOPA) (222), tryptophan (222), aminoiso-butyric acid (219), 2-aminobutyric acid (219,231), citrulline (222), and ornithine (222). 

A series of 1-aminoalkanediphosphonic acids has been reported by the treatment of the N-phenylthiourea derivatives of a>-diethoxyphos-phinoylaldehydes with triphenyl phosphite.343 This constitutes an approach toward the analogues of aspartic and glutamic acid in which both carboxylate sites have been replaced by phosphonic acid functions. A similar approach has also been reported to be of use for the preparation of (diphenyl ester) phosphonate analogues of ornithine, lysine, and homolysine.344345... 

Hamilton, R., Walker, B., and Walker, B.J., A convenient synthesis of N-pro-tected diphenyl phosphonate ester analogues of ornithine, lysine and homolysine, Tetrahedron Lett., 34, 2847, 1993. 

In animal studies, mirex (a nonmutagenic hepatocarcinogen) promoted mouse skin squamous carcinomas and papillomas after initiation with 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. Mirex, also, potentiated the promotional potency of the phorbol ester tumor promoter, 12-0 -tetradecanoylphorbol-13-acetate (TPA). There was a 90% incidence (activation) of the c-Ha-ras tumor gene in these co-promoted tumors. When both mirex and TPA gave a similar tumor yield, only the TPA response was associated with biochemical markers of enhanced cell proliferation, induction of epidermal ornithine decarboxylase activity and increased DNA synthesis, and hyperplasia. Thus, there is evidence for a dual effect of mirex during co-promotion first, as an independent tumor promoter with a mechanism different than that of phorbol esters and second, as a compound that also potentiates skin tumor promotion by TPA (Meyer et al. 1993, 1994 Moser et al. 1992, 1993). 

Fig. 10. The mechanism of site-selective amidation of lysine residues in folded hehcal structures with His (i) Lys (i -t 4 or i-3) sites. The ester is typically p-nitrophenyl but can also be e.g. JV-hydroxysuccinimidyl. Ornithine and diaminobutyric acid residues will also be amidat-ed in the described positions...

It was also synthesised by E. Fischer in 1901 from 7-phthalimido-propylmalonic ester which he employed in the preparation of ornithine. The bromine derivative of this compound when treated with ammonia gave a complex mixture of products which after hydrolysis by hydrochloric acid at 100° C. gave phthalimide and a-pyrrolidine carboxylic acid —... 

ZO024 Park, K. K., K. S. Chum, ]. M. Lee, S. S. Lee, and Y. ]. Surh. Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett 1998 129(2) 139-144. 

Luyengi, L. et al., Rotenoids and chalcones from Mundulea sericea that inhibit phorbol ester-induced ornithine decarboxylase activity. Phytochemistry, 36, 1523, 1994. 

Several 0-aminoacyl sugars were prepared to study a relationship between taste and chemical structure. Methyl a-D-glucopyranoside, methyl a-D-galactopyranoside and methyl a-D-mannopyranoside were selected as sugar skeletons. As basic amino acids, esters of lysine, ornithine, a,Y-diaminobutyric acid, and a,p-diaminopropionic acid were introduced into 2-0-, 3-0-, and 4-0- positions of sugars leaving only 6-hydroxyl group free. The results of sensory analysis are list in Table VI. O-... 

Some species of cellular slime molds use other chemical attractants (acrasins). For example, D. minutum secretes an analog of folic acid1 and cells of Polysphondylium violaceum are attracted by the ethyl ester of N-propionyl-y-L-glutamyl-L-ornithine-8-lactam.s... 

Ornithine decarboxylase 342, 342s Ornithine mutases 871, 874 Oscillatoria 22 Osmate ester 393s Osmotic shock 417 Osteoarthritis 438 Osteoblasts 26, 441... 

The mechanisms by which antitumor-promoters suppress the tumor promotion are not known, but may be due to the following effects (i) inhibition of polyamine metabolism (ii) inhibition of arachidonic acid metabolism (iii) protease inhibition (iv) induction of differentiation (v) inhibition of oncogene expression (vi) inhibition of PKC and (vii) inhibition of oxidative DNA damage [3,6,91]. The polyamine content of cells is correlated to their proliferative, and often, their neoplastic capabilities. A key enzyme in the polyamine biosynthetic pathway, ornithine decarboxylase (ODC), catalyzes the convertion of ornithine to putrescine. Phorbol ester promoters such as TPA cause increased ODC activity and accumulation of polyamines in affected tissues. Diacylglycerol activated PKC, and the potent tumor promoter, TPA, binds to, and activates PKC, in competition with diacylglycerol. PKC stimulation results in phosphorylation of regulatory proteins that affect cell proliferation. Some chemopreventive agents have inhibitory activity towards PKC. Refer to recent review articles for further discussion [3,6,91]. 

Scheme 13 Synthesis of Diphenyl Esters of Phosphonic Analogues of Ornithine, Lysine, and Homolysinel371...

Use of the preformed Z-silyl enol ether 18 results in quite substantial anti/syn selectivity (19 20 up to 20 1), with enantiomeric purity of the anti adducts reaching 99%. The chiral PT-catalyst 12 (Schemes 4.6 and 4.7) proved just as efficient in the conjugate addition of the N-benzhydrylidene glycine tert-butyl ester (22, Scheme 4.8) to acrylonitrile, affording the Michael adduct 23 in 85% yield and 91% ee [10]. This primary product was converted in three steps to L-ornithine [10]. The O-allylated cinchonidine derivative 21 was used in the conjugate addition of 22 to methyl acrylate, ethyl vinyl ketone, and cydohexenone (Scheme 4.8) [12]. The Michael-adducts 24-26 were obtained with high enantiomeric excess and, for cydohexenone as acceptor, with a remarkable (25 1) ratio of diastereomers (26, Scheme 4.8). In the last examples solid (base)-liquid (reactants) phase-transfer was applied. 

N-a-Carbobenzoxy-N-8-toluenesulfonyl-L-ornithine Glycine ethyl ester... 

Michael addition of glycinate Schiff base 28 to a,/ -unsaturated carbonyl substrates with high enantioselectivity (Scheme 4.19) [53, 54]. With methyl acrylate as an acceptor, a-tert-butyl y-methyl ester of (S)-glutamic acid can be formed this functionalized glutamic acid derivative is very useful for synthetic applications because the two carboxyl groups are differentiated. Moreover, naturally occurring (S)-ornithine has been synthesized as its dihydrochloride in a concise manner by using acrylonitrile as an acceptor, as also included in Scheme 4.19... 

Gupta, A.K., Fisher, G.J., Elder, J.T., Nickoloff, B.J., and Voorhees, J.J., Sphingosine inhibits phorbol ester-induced inflammation, ornithine decarboxylase activity, and activation of protein kinase C in mouse skin, J. Invest. Dermatol., 91, 486-491, 1988. 

Zanetta and Vincendon [237] preferred N-HFB-isoamyl esters of amino acids, which reputedly can be concentrated without any loss of material. They obtained a very good separation of these derivatives of all protein amino acids, including kynurenine and ornithine, on a 3.5-m column packed with 3% of SE-30 on Gas-Chrom Q. The analysis took about 40 min with temperature programming. 

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