1.Radiosynthesis of 1-[18F]fluoroethyl-L-tryptophan as a novel potential amino acid PET tracer.
Sun T1, Tang G, Tian H, Wang X, Chen X, Chen Z, Wang S. Appl Radiat Isot. 2012 Apr;70(4):676-80. doi: 10.1016/j.apradiso.2011.11.062. Epub 2011 Dec 7.
(18)F labeled natural amino acids have been introduced as promising tumor imaging agents. A novel [(18)F]fluoro amino acid analog 1-[(18)F]fluoroethyl-L-tryptophan (1-[(18)F]FETrp) was designed and synthesized by a two-pot three-step procedure, including the synthesis of 1-[(18)F]fluoro-2- (tosyloxy)ethane, the [(18)F]fluoroethylation of the precursor N-Boc-L-tryptophan ethyl ester and following the deprotection of the tert-butoxycarbonyl and ethyl ester protecting groups. 1-[(18)F]FETrp was resulted in 0.9 ± 0.2% (n=5) radiochemical yields (no decay corrected) by HPLC purification, within a total synthesis time of 65 min. The radiochemical purity of 1-[(18)F]FETrp was 95-97%. The radiosynthetic method needs to be further optimized to get a satisfying radiochemical yield.
2.Synthesis of D-abrines by palladium-catalyzed reaction of ortho-iodoanilines with N-Boc-N-methylalanyl-substituted acetaldehyde and acetylene.
Danner P1, Morkunas M, Maier ME. Org Lett. 2013 May 17;15(10):2474-7. doi: 10.1021/ol4009409. Epub 2013 Apr 30.
A novel strategy to N-Boc-N-methyl--tryptophans (abrine derivatives) was developed that relies on the palladium-catalyzed annulation of ortho-iodoanilines 12 with either N-Boc-N-methyl-propargylglycine 16 or aldehyde 11. Both 11 and 16 can be prepared from d-serine. An alternative route to propargylglycine 16 utilizes an enantioselective propargylation reaction of glycine imine 17.
3.Thiol-targeted introduction of selenocysteine to polypeptides for synthesis of glutathione peroxidase mimics.
Haratake M1, Sakano T, Fuchigami T, Nakayama M. Metallomics. 2011 Jul;3(7):702-9. doi: 10.1039/c1mt00001b. Epub 2011 Mar 1.
Because the seleno-l-cysteine (SeCys or Sec) insertion into selenoproteins occurs by a specific translational control process, it is quite difficult to express the SeCys-containing polypeptides even by the state-of-the-art genetic engineering techniques. In this paper, we describe a convenient synthetic method for the selective introduction of a SeCys derivative to polypeptides under physiological conditions. One SeCys residue in the seleno-l-cystine (SeCys-Se-Se-SeCys) methyl ester was first substituted with the Boc-protected penicillamine (Pen) methyl ester to form selenenylsulfide (SeCys-Se-S-Pen), an intermediate in the cellular glutathione peroxidase (GPx) catalytic cycle. Subsequently, the SeCys-Pen was coupled with the thiol-specific N-carboxymethylmaleimide through the α-amino group of the SeCys {[2-(N-maleimidyl)-1-oxo-ethyl-SeCys-methyl-Se-yl]-S-Pen methyl ester, MOE-SeCys-Pen}. The use of the MOE-SeCys-Pen allowed the selective introduction of the SeCys moiety to human serum albumin by alkylation of the thiol at its cysteine34, which generated the GPx-like activity responsible for the selenium atom in the MOE-SeCys-Pen.
4.Selective C-2 alkylation of tryptophan by a Pd(II)/norbornene-promoted C-H activation reaction.
Potukuchi HK1, Bach T. J Org Chem. 2013 Dec 6;78(23):12263-7. doi: 10.1021/jo402107m. Epub 2013 Nov 15.
A palladium(II)-catalyzed norbornene-mediated regioselective alkylation at the C-2 indole position of N-tert-butyloxycarbonyl (Boc)-protected (S)-tryptophan ethyl ester is reported. The protocol employs mild reaction conditions and is tolerant of a range of functional groups. The reaction proceeds without racemization at the stereogenic center of the amino acid.
