Tyrosine derivatives, synthesis

Initially, the cytotoxicity against chick embryo fibroblasts of BPA, tyrosine, tyrosine dipeptide, and the dipeptide derivatives used in the synthesis of the polymers shown in Fig. 7 were evaluated in a comparative experiment (43). The surface of standard tissue culture wells was coated with 5 mg of each test substance. Then the adhesion and proliferation of the fibroblasts was followed over a 7-day period. Among all test substances, BPA was clearly the most cytotoxic material. Monomeric tyrosine derivatives containing the ben-zyloxycarbonyl group were also cytotoxic, while tyrosine itself, tyrosine dipeptide, and most of the protected dipeptide derivatives did not noticeably interfere with cell growth and adhesion and were therefore classified on a preliminary basis as possibly "nontoxic."... 

Synthesis of Tyrosine Derivatives. Tyrosine derived monomers were prepared by DCC mediated coupling reactions in THF following standard procedures of peptide chemistry (72). Dat-Tym, Z-Tyr-Tym, Z-Tyr-Tyr-Hex, and Dat-Tyr-Hex (DTH) were purified and characterized according to reference 10. For spectral data of Z-Tyr-Tyr-Hex, see Kohn and Langer (75). 

The author acknowledges the assistance of Mr. Israel Engelberg, who performed some of the mechanical tests. The X-ray diffraction data were collected in the laboratory of Professor M. Greenblatt (Department of Chemistry, Rutgers University) by Ms. Aruna Nathan. The author thanks Mr. Chun Li and Mr. Satish Pulapura for their part in the synthesis and characterization of tyrosine derived polymers. 

Fetterer, R.H., Rhoads, M.L. and Urban, J.F. (1993) Synthesis of tyrosine-derived cross-links in Ascaris suum cuticular proteins. Journal of Parasitology 79,160-166. 

Thioamides are reducing agents. They inhibit thyroid hormone synthesis by inhibiting the peroxidase enzymatic system, which catalyzes oxidation of iodide ions and iodine that are consumed in food, which is necessary for iodination of tyrosine derivatives. Thus they reduce the concentration of free iodine necessary to react with tyrosine derivatives, and they can also block oxidative addition reactions of mono- and diiodtyrosines, which form L-thyroxine and L-triiodothyronin. 

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). 

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

Boehlow TR, Harbum JJ, Spilling CD (2001) Approaches to the Synthesis of Some Tyrosine-Derived Marine Sponge Metabolites Synthesis of Verongamine and Purealidin N. J Org Chem 66 3111... 

Kotoku N, Tsujita H, Hiramatsu A, Mori C, Koizumi N, Kobayashi M (2005) Efficient Total Synthesis of Bastadin 6, an Anti-Angiogenic Brominated Tyrosine-Derived Metabolite from Marine Sponge. Tetrahedron 61 7211... 

In an analogous fashion, total synthesis of cytotoxic marine alkaloid, gym-nastatin A (24), which was isolated from the sponge Halicondria japonica, was accomplished via the spirolactol (143) derived from the tyrosinal derivative (142) with PIFA [101] (Scheme 15). 

Jensen KJ, Meldal M, Bock K, Glycosilation of phenols preparation of 1,2- cis and 1,2- trans glycosylated tyrosine derivatives to be used in solid-phase glycopeptide synthesis, J. Chem. Soc. Perkin. Trans., 1, 2119, 1993. 

An approach to the key precursor 38 in the synthesis of 9,10-disubstituted analogs 39 implemented the introduction of chirality with the L-tyrosine derivative 37 (Scheme 2) <1999JOC6366>. A similar synthesis was reported for 9-substituted analogs of BL-V8 16 <1998TL7369>. 

Resin bound carbodiimides are used in the formation of diphenol monomers used in the synthesis of tyrosine derived pseudo polypeptides. ... 

Tyrosine spirolactones are not only promising synthetic intermediates for bioactive natural products such as alkaloids and antibiotics but also synthons useful in peptide chemistry. For example, N-protected tyrosine derivatives 104 and 105, prepared from 2,6-di(ferf-butyl)-4-chloromethylphenol, were electrolyzed at a controlled potential (+1.3-1.4 V Vi. Ag/Ag+) in MeCN to give spirolactones 106 and 107 (64 and 85%, respectively). These spirolactones are used for peptide synthesis, as shown in Scheme 19. 

Fukuoka, T., Tachibana, Y., Tonami, H., Uyama, H., and Kobayashi, S. (2002) Enzymatic polymerization of tyrosine derivatives. Peroxidase- and protease-catalyzed synthesis of Poly(Tyrosine)s with different structures. Biomacromolecules, 3 (4), 768-774. 

The synthesis of the spirocyclic core [70-77] is obviously the most difficult task, the biomimetic approach being the most frequent way of preparing it. The strategy is based on the hipervalent iodine-mediated oxidative hydroxylation of a tyrosinal derivative followed by a cis-bisepoxidation. The shortest way [75] involved the introduction of the side chain as an amide of tyrosine ethyl ester. Aranorosin was obtained after DIBAL reduction to the aldehyde, oxidation to the dienone with phenyliodosyl bis(trifluoroacetate) (PIFA) and final epoxidation (Scheme 24). 

In 2001, Funk reported a synthesis of ( )-FR901483 using an approach very different from those described previously, taking advantage of his amidoacrolein cycloaddition methodology to prepare 1 -alkyl-1 -aminocyclohexane derivatives, starting the synthesis from acyclic compounds. Moreover, Funk neither uses tyrosine derivatives nor needs an inversion at C(9) to install the phosphate unit. In Funk s retro synthetic analysis, shown in Scheme 23, he envisaged that lactam 60 possessed the necessary functionality for the introduction of the C(6) p-methoxy benzyl and C(3) methylamino substituents via enolate alkylation and amination reactions, respectively. 

Phenoxides undergo substitution for chloride [58-60]. The first substitution in a dichlorobenzene complex occurs at -20 °C [61]. This allowed synthesis of tyrosine derivative 33 without the loss of optical purity [62a]. 

This methodology has been applied to the multistep synthesis of a sulfonylated tyrosine derivative, a highly potent analog of the antithrombic drug tirofiban according to Scheme 5.5-30. The target compound was obtained in 11% yield over 5 steps after purification by preparative HPLC (Scheme 5.5-35). 

Z. Dong, Synthesis of Four Structurally Related Tyrosine-Derived Polycarbonates and In Vitro Study of Dopamine Release from Poly(Desaminotyrosyl-Tyrosine Hexyl Ester Carbonate), Master s Thesis, Rutgers University, New Bnmswick, NJ, 1993. 

Figure 2 Synthesis of tyrosine-derived polyarylates. DIPC, 1,3-diisopropylcarbodiimide DMAP, dimethylaminopyridine PTSA, p-toluenesulfonic acid.

Magno, M.H.R., et al. 2010. Synthesis, degradation and biocompatibility of tyrosine-derived polycarbonate scaffolds. Journal of Materials Chemistry 20(40) 8885-8893. 

DESIGN AND SYNTHESIS OF TYROSINE DERIVED POLYMERS Monomer Design and Synthesis... 

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