Abstract
Natural l-homocysteine and l,l-cystathionine, along with a series of unnatural analogues, have been prepared from l-aspartic and l-glutamic acid. Manipulation of the protected derivatives provided ω-iodoamino acids, which were used in thioalkylation reactions of sulfur nucleophiles, such as the ester of l-cysteine and potassium thioacetate.
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Abbreviations
- All:
-
Allyl
- Bn:
-
Benzyl
- Boc:
-
tert-Butoxycarbonyl
- Cth:
-
Cystathionine
- Hcy:
-
Homocysteine
- DCC:
-
N,N′-Dicyclohexylcarbodiimide
- Fm:
-
9-Fluorenylmethyl
- Fmoc:
-
9-Fluorenylmethoxycarbonyl
- HOBt:
-
1-Hydroxybenzotriazole
- ImH:
-
Imidazole
- NMM:
-
N-Methylmorpholine
- Nva:
-
Norvaline
- Pg:
-
Protecting group
- SPPS:
-
Solid-phase peptide synthesis
- THF:
-
Tetrahydrofurane
- TPP:
-
Triphenylphosphine
References
Bolognese A, Fierro O, Guarino D, Longobardo L, Caputo R (2006) One-pot synthesis of orthogonally protected enantiopure S-(aminoalkyl)-cysteine derivatives. Eur J Org Chem 1:169–173
Caputo R, Longobardo L (2007) Enantiopure β3-amino acids-2,2–d2 via homologation of proteinogenic α-amino acids. Amino Acids 32:401–404
Caputo R, Cassano E, Longobardo L, Palumbo G (1995a) Chiral N-protected β-iodoamines from α-amino acids: a general synthesis. Tetrahedron Lett 36:167–168
Caputo R, Cassano E, Longobardo L, Palumbo G (1995b) Synthesis of enantiopure N-and C-protected homo-β-amino acids by direct homologation of α-amino acids. Tetrahedron 51:12337–12350
Caputo R, Capone S, DellaGreca M, Longobardo L, Pinto G (2007) Novel selenium-containing non-natural diamino acids. Tetrahedron Lett 48:1425–1427
Caputo R, DellaGreca M, de Paola I, Mastroianni D, Longobardo L (2010) Novel sulfur and selenium containing bis-α-amino acids from 4-hydroxyproline. Amino Acids 38:305–310
Dekan Z, Vetter I, Daly NL, Craik DJ, Lewis RJ, Alewood PF (2011) α-Conotoxin ImI incorporating stable cystathionine bridges maintains full potency and identical three-dimensional structure. J Am Chem Soc 133:15866–15869
Finkelstein JD, Martin JJ (1984) Methionine metabolism in mammals. J Biol Chem 259:9508–9513
Frimpter GW (1965) Cystathioninuria: nature of the defect. Science 149:1095–1096
Galande AK, Trent JO, Spatola AF (2003) Understanding base-assisted desulfurization using a variety of disulfide-bridged peptides. Biopolymers (Peptide Sci) 71:534–551
Jones DS, Gamino CA, Randow ME, Victoria EJ, Yu L, Coutts SM (1998) Synthesis of a cyclic-thioether peptide which binds anti-cardiolipin antibodies. Tetrahedron Lett 39:6107–6110
Kanzaki H, Kobayashi M, Nagasawa T, Yamada H (1987) Production of l-cystathionine using bacterial cystathionine γ-synthase. Appl Microbiol Biotechnol 25:322–326
Khalaf JK, VanderVelde DG, Datta A (2008) Synthetic studies on ezomycins: stereoselective route to a thymine octosyl nucleoside derivative. J Org Chem 73:5977–5984
Knapp S, Gore VK (2000) Synthesis of the ezomycin nucleoside disaccharide. Org Lett 2:1391–1393
Knerr PJ, Tzekou A, Ricklin D, Qu H, Chen H, van der Donk WA, Lambris JD (2011) Synthesis and activity of thioether-containing analogues of the complement inhibitor Compstatin. ACS Chem Biol 6:753–760
Kokotos G (1990) A convenient one-pot conversion of N-protected amino acids and peptides into alcohols. Synthesis 299–301
Kondo Y (1962) The cystathionine pathway in the silkworm larva, Bombyx mori. J Biochem 51:188–192
Koseki Y, Yamada H, Usuki T (2011) Efficient synthesis of benzyl 2-(S)-[(tert-butoxycarbonyl) amino]-ω-iodoalkanoates. Tetrahedron Asymmetry 22:580–586
Mason JB (2003) Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism. J Nutr 133:941S–9417S
Mayer JP, Heil JR, Zhang J, Munson MC (1995) An alternative solid-phase approach to C1-oxytocin. Tetrahedron Lett 36:7387–7390
Nigam SN, McConnell WB (1972) Isolation and identification of l-cystathionine and l-selenocystathionine from the foliage of Astragalus pectinatus. Phytochemistry 11:377–380
Perrey DA, Uckun FM (2001) An improved method for cysteine alkylation. Tetrahedron Lett 42:1859–1861
Rajagopal D, Eckhardt M, Furlong M, Knoess HP, Berger S, Knochel P (1994) Preparation and reactivity of chiral related configurationally stable zinc organometallics. Tetrahedron 50:2415–2432
Salvatore RN, Smith RA, Nischwitza AK, Terrence GT (2005) A mild and highly convenient chemoselective alkylation of thiols using Cs2CO3–TBAI. Tetrahedron Lett 46:8931–8935
Shiraiwa T, Nakagawa K, Kanemoto N, Kinda T, Yamamoto H (2002) Synthesis of optically active homocysteine from methionine and its use in preparing four stereoisomers of cystathionine. Chem Pharm Bull 50:1081–1085
Tabor AB (2011) The challenge of the lantibiotics: synthetic approaches to thioether-bridged peptides. Org Biomol Chem 9:7606–7628
Townsend DM, Tew KD, Tapiero H (2004) Sulfur containing amino acids and human disease. Biomed Pharmacother 58:47–55
Włostowski M, Czarnocka S, Maciejewski P (2010) Efficient S-alkylation of cysteine in the presence of 1,1,3,3-tetramethylguanidine. Tetrahedron Lett 51:5977–5979
Yamagata S, Akamatsu T, Iwama T (2004) Immobilization of Saccharomyces cerevisiae cystathionine γ-lyase and application of the product to cystathionine synthesis. Appl Environ Microbiol 70:3766–3768
Zhu X, Schmidt RR (2003) Efficient synthesis of differently protected lanthionines via β-bromoalanine derivatives. Eur J Org Chem 4069–4072
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Longobardo, L., Cecere, N., DellaGreca, M. et al. Novel thiol- and thioether-containing amino acids: cystathionine and homocysteine families. Amino Acids 44, 443–448 (2013). https://doi.org/10.1007/s00726-012-1352-5
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DOI: https://doi.org/10.1007/s00726-012-1352-5