FMOC-D-CIT-OH

White solid

100 g of Rink Amide AM Resin was Suspended to Swell in 1000 mL of Dimethylformamide at 25-30 C. for 3-4 Hrs Under Slow Stirring (0058) The solvent was then removed under vacuum. The dried resin was then treated with 500 mL of 20% piperidine in dimethyl formamide for 10-15 min at 25-30 C. and dried under vacuum. Further, the resin so obtained was treated alternatively with 500 mL of dimethyl formamide and 500 mL of dichloromethane several times and dried under vacuum. (0059) In another clean and dry round bottom flask, 70 g of Fmoc-D-Ala-OH was dissolved in 400 mL of dimethylformamide at 25-30 C. and 30 g of HOBt was added. The reaction mixture was cooled to 0-5 C. and stirred for 10-15 mins. 55 mL of N, N?-diisopropylcarbodiimide (DIC) was then added to the reaction mixture at 0-5 C. (0060) The activated amino acid (Fmoc-D-Ala-OH) solution was then added to the dried Rink amide AM resin and stirred for 2-3 hrs at 25-30 C. On completion of reaction, 600 mL of dimethyl formamide was added to the reaction mass and stirred for 5-10 min at 25-30 C. The total reaction mass was dried under vacuum and the residue was treated with 600 mL of dichloromethane and dried under vacuum at 25-30 C. The same process was followed with 600 mL of dimethyl formamide and the solvent removed under vacuum. (0061) The residue so obtained was then treated with 500 mL of dimethylformamide, acetic anhydride and pyridine mixture and dried under vacuum. The dried resin was then treated with 600 mL of dimethyl formamide, stirred for 10-15 mins and dried under vacuum. Further, the same process was repeated with 600 mL of dichloromethane followed by 600 mL of dimethyl formamide to obtain the dried resin of Fmoc-D-Ala-NH-Rink amide resin (12). Example-2: Preparation of Protected Peptide-Rink Amide Resin (3) (0062) The Fmoc-D-Ala-NH-Rink amide resin (12) was treated with 600 mL of 20% in piperidine in dimethyl formamide at 25-30 C. temperature. The reaction mass was stirred for 10-15 min and solvent was removed under vacuum. The residue was treated again with 600 mL of 20% in piperidine in dimethyl formamide at 25-30 C. To this amino acids were coupled in the said order, wherein the order of amino acids was Fmoc-D-alanine, Fmoc-L-proline, Fmoc-D-Arginine(Pbf), Fmoc-L-leucine, General procedure: Amino acids, building blocks, coupling reagents and Wang resins were purchased from Novabiochem AG. The glycosylated amino acids were prepared in our lab following procedures as reported in our previous work. 1 All reagents used for synthesis were from analytical grade. Peptides were synthesized manually following standard solid-phase methods and Fmoc protocols on Wang resin using amino acids with orthogonal protections on lateral chains. Amide couplings were performed manually ina peptide synthesis column using DIC/HOBt in DMF under reciprocal oscillating agitation. Coupling efficiencies were monitored by Kaiser ninhydrin test. Fmoc groups were removed with a 20% piperidine in DMF solution. Peptides and glycopeptides were cleaved from the resin by shaking with a cleavage cocktail consisting of TFA:H2O:TIS(95:2.5:2.5) for 2 h. The filtrate was evaporated, washed several times with ice-cold tert-butyl methyl ether and concentrated under reduced pressure. The crude glycopeptides were precipitated with ice-cold tert-butyl methyl ether, filtered, redissolved in water and lyophilized. In the case of glycopeptides, the acetyl protecting groups on the sugar moieties were next hydrolyzed carefully adding sodium methoxide/MeOH solutions to methanol solutions of the protected glycopeptides (monitored by analytical reverse-phase HPLC). The glycopeptides were neutralized by addition of AcOH and concentrated under reduced pressure. Crude peptides and glycopeptides were purified by C-18 RP-HPLC (VersaFlashTM Flash Chromatograph ysystem) using a water-acetonitrile gradient and followed by lyophilization. The final pure peptides were characterized by HRMS. Analytical RP-HPLC were performed using the following solvents A (0.1% TFA in H2O) and B (0.1% TFA in acetonitrile) and the Nucleosil 100 RP-18 (5mum) C18 column (4x 250 mm).General procedure: All peptides were synthesized manually by Fmoc-based solid phase peptide synthesis (SPPS) on 2-chlorotritylchloride resin (0.15 mmol scale). The first amino acid (Fmoc-Gly-OH or Fmoc-beta-Ala-OH) was loaded onto the resin by use of 2 eq. Fmoc-protected amino acid with 4 eq. DIPEA in CH2Cl2 for 2 h. The remaining chlorines were substituted by treatment of the resin with a mixture of MeOH/CH2Cl2/DIPEA (2:17:1) during 4 times 5 min. For normal couplings, a 3-fold excess of the Fmoc-protected amino acids (Fmoc-D-Arg(Pbf)-OH, Synthesis of the peptide is carried out by a regular stepwise Fmoc SPPS procedure starting from 2-Cl-Trt-chloride resin. The first amino acid (Fmoc-D-Ala) is loaded on the resin as described in previous examples to obtain a loading of about 0.7 mmol/g of amino acid/resin. After washing of the resin and removal of the Fmoc group by treatment with piperidine/DMF, the second amino acid (Fmoc-Pro) is introduced to continue sequence elongation. Fmoc protected amino acids are activated in situ using TBTU/HOBt and subsequently coupled to the resin over about 50 minutes. Diisopropylethylamine or collidine is used during coupling as an organic base. Completion of the coupling is indicated by ninhydrin test. After washing of the resin, the Fmoc protecting group on the alpha-amine is removed with 20% piperidine in DMF for 20 min. These steps are repeated each time with another amino acid according to the peptide sequence. All amino acids used are Fmoc-Nalpha protected. Trifunctional amino acids are side chain protected as follows: Tyr(tBu) and Ser(tBu). Three equivalents of the activated amino acids are used in the coupling reactions. At the end of the synthesis, the Fmoc group at the N-terminus is removed and the amino group is acetylated by acetic anhydride. The peptide-resin is washed with DMF, followed by DCM, and dried under vacuum to obtain dry peptide-resin.Synthesis of the peptide is carried out by a regular stepwise Fmoc SPPS procedure starting from 2-Cl-Trt-chloride resin. The first amino acid (Fmoc-D-Ala) is loaded on the resin as described in previous examples to obtain a loading of about 0.7 mmol/g of amino acid/resin. After washing of the resin and removal of the Fmoc group by treatment with piperidine/DMF, the second amino acid (Fmoc-Pro) is introduced to continue sequence elongation. Fmoc protected amino acids are activated in situ using TBTU/HOBt and subsequently coupled to the resin over about 50 minutes. Diisopropylethylamine or collidine is used during coupling as an organic base. Completion of the coupling is indicated by ninhydrin test. After washing of the resin, the Fmoc protecting group on the alpha-amine is removed with 20% piperidine in DMF for 20 min. These steps are repeated each time with another amino acid according to the peptide sequence. All amino acids used are Fmoc-Nalpha protected. Trifunctional amino acids are side chain protected as follows: Arg(Pbf), Tyr(tBu), and Ser(tBu). Three equivalents of the activated amino acids are used in the coupling reactions. After addition of the last amino acid (Fmoc-D-Nal), and removal of the Fmoc protecting group, the N-terminus is acetylated by acetic anhydride. At the end of the synthesis, the peptide-resin is washed with DMF, followed by DCM, and dried under vacuum to obtain dry peptide-resin.

Molecular Weight:397.4
XLogP3:2.1
Hydrogen Bond Donor Count:4
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:9
Exact Mass:397.16377084
Monoisotopic Mass:397.16377084
Topological Polar Surface Area:131
Heavy Atom Count:29
Complexity:577
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes