Fmoc-Cys(Trt)-OH

Fmoc-Cys(Trt)-OH

Liquid and subcritical fluid chromatographic enantioseparation of N(alpha) -Fmoc proteinogenic amino acids on Quinidine-based zwitterionic and anion-exchanger type chiral stationary phases. A comparative study.[Pubmed:28422383]

Chirality. 2017 Jun;29(6):225-238.

Stereoselective high-performance liquid chromatographic and subcritical fluid chromatographic separations of 19 N(alpha) -Fmoc proteinogenic amino acid enantiomers were carried out by using Quinidine-based zwitterionic and anion-exchanger-type chiral stationary phases Chiralpak ZWIX(-) and QD-AX. For optimization of retention and enantioselectivity, the ratio of bulk solvent components (MeOH/MeCN, H2 O/MeOH, or CO2 /MeOH) and the nature and concentration of the acid and base additives (counter- and co-ions) were systematically varied. The effect of column temperature on the enantioseparation was investigated and thermodynamic parameters were calculated from the van't Hoff plots ln alpha vs. 1/T. The thermodynamic parameters revealed that the enantioseparations were enthalpy-driven. The elution sequence was determined in all cases and with the exception of Fmoc-Cys(Trt)-OH, it was identical on both chiral stationary phases whereby the L-enantiomers eluted before the D-enantiomers.

Acid-labile Cys-protecting groups for the Fmoc/tBu strategy: filling the gap.[Pubmed:23075170]

Org Lett. 2012 Nov 2;14(21):5472-5.

To address the existing gap in the current set of acid-labile Cys-protecting groups for the Fmoc/tBu strategy, diverse Fmoc-Cys(PG)-OH derivatives were prepared and incorporated into a model tripeptide to study their stability against TFA. S-Dpm proved to be compatible with the commonly used S-Trt group and was applied for the regioselecive construction of disulfide bonds.

A 'conovenomic' analysis of the milked venom from the mollusk-hunting cone snail Conus textile--the pharmacological importance of post-translational modifications.[Pubmed:24055806]

Peptides. 2013 Nov;49:145-58.

Cone snail venoms provide a largely untapped source of novel peptide drug leads. To enhance the discovery phase, a detailed comparative proteomic analysis was undertaken on milked venom from the mollusk-hunting cone snail, Conus textile, from three different geographic locations (Hawai'i, American Samoa and Australia's Great Barrier Reef). A novel milked venom conopeptide rich in post-translational modifications was discovered, characterized and named alpha-conotoxin TxIC. We assign this conopeptide to the 4/7 alpha-conotoxin family based on the peptide's sequence homology and cDNA pre-propeptide alignment. Pharmacologically, alpha-conotoxin TxIC demonstrates minimal activity on human acetylcholine receptor models (100 muM, <5% inhibition), compared to its high paralytic potency in invertebrates, PD50 = 34.2 nMol kg(-1). The non-post-translationally modified form, [Pro](2,8)[Glu](16)alpha-conotoxin TxIC, demonstrates differential selectivity for the alpha3beta2 isoform of the nicotinic acetylcholine receptor with maximal inhibition of 96% and an observed IC50 of 5.4 +/- 0.5 muM. Interestingly its comparative PD50 (3.6 muMol kg(-1)) in invertebrates was ~100 fold more than that of the native peptide. Differentiating alpha-conotoxin TxIC from other alpha-conotoxins is the high degree of post-translational modification (44% of residues). This includes the incorporation of gamma-carboxyglutamic acid, two moieties of 4-trans hydroxyproline, two disulfide bond linkages, and C-terminal amidation. These findings expand upon the known chemical diversity of alpha-conotoxins and illustrate a potential driver of toxin phyla-selectivity within Conus.

Stereoselective Polymer-Supported Synthesis of Morpholine- and Thiomorpholine-3-carboxylic Acid Derivatives.[Pubmed:28085245]

ACS Comb Sci. 2017 Mar 13;19(3):173-180.

Herein we report the polymer-supported synthesis of 3,4-dihydro-2H-1,4-oxazine-3-carboxylic acid derivatives using immobilized Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH as the starting materials. After the solid-phase-synthesis of N-alkyl-N-sulfonyl/acyl intermediates, the target dihydrooxazines were obtained using trifluoroacetic acid-mediated cleavage from the resin. This approach was also studied for the preparation of dihydrothiazines from immobilized Fmoc-Cys(Trt)-OH. Inclusion of triethylsilane in the cleavage cocktail resulted in the stereoselective formation of the corresponding morpholine/thiomorpholine-3-carboxylic acids. Stereochemical studies revealed the specific configuration of the newly formed stereocenter and also the formation of stable N-acylmorpholine rotamers.

Parallel Synthesis of Structurally Diverse Aminobenzimidazole Tethered Sultams and Benzothiazepinones.[Pubmed:23209332]

Tetrahedron Lett. 2012 Dec 19;53(51):6897-6900.

A solid-phase methodology to construct aminobenzimidazole tethered sultams and benzothiazepinones from commercial amino acids, amines, carboxylic acids and sulfonyl chlorides is described. Coupling of Fmoc-Cys(Trt)-OH to resin-bound aminobenzimidazole scaffold provided an essential precursor for the construction of a variety of seven membered benzofused cyclic sulfonamides and thiazepinones via palladium catalyzed Buchwald-Hartwig type intramolecular cyclization.