Name: 169555-95-7|Fmoc-4-Pal-OH|97%
Brand: Ambeed
SKU: A126551
Price: 6.0 USD
Availability: InStock
Rating: 95 (28 reviews)

1
[ 82911-69-1 ]
[ 37535-49-2 ]
[ 169555-95-7 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 1335 - 1340

2
[ 169555-95-7 ]
(S)-4-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-carboxyethyl)pyridine 1-oxide [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 4709 - 4712
[2]Journal of the Chemical Society. Perkin transactions I,1995,p. 1335 - 1340

3
[ 108-24-7 ]
[ 91000-69-0 ]
[ 109425-51-6 ]
[ 169555-95-7 ]
[ 143824-78-6 ]
Ac-His-4Pal-Arg-Trp-NH₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3073 - 3081

4
[ 108-24-7 ]
[ 86123-10-6 ]
[ 109425-51-6 ]
[ 169555-95-7 ]
Fmoc-Arg(Pbf)-OH [ No CAS ]
Ac-His-D-Phe-Arg-4Pal-NH₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5736 - 5744

5
[ 123-75-1 ]
[ 50-00-0 ]
[ 107-15-3 ]
[ 169555-95-7 ]
[1-(2,6-dichloro-benzyl)-1H-indol-6-yl]-carbamic acid 4-nitro-phenyl ester [ No CAS ]
(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(2-fluorophenyl)propanoic acid [ No CAS ]
N-[1-(2-amino-ethylcarbamoyl)-2-pyridin-4-yl-ethyl]-2-{3-[1-(2,6-dichloro-benzyl)-3-pyrrolidin-1-ylmethyl-1H-indol-6-yl]-ureido}-3-(2-fluoro-phenyl)-propionamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2199 - 2203

6
[ 23159-07-1 ]
[ 92-95-5 ]
[ 169555-95-7 ]
(S)-2-(3-biphenyl-4-yl-ureido)-3-pyridin-4-yl-N-(3-pyrrolidin-1-yl-propyl)-propionamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4477 - 4492

7
[ 23159-07-1 ]
[ 59377-19-4 ]
[ 169555-95-7 ]
2-[3-(4-phenoxy-phenyl)-ureido]-3-pyridin-4-yl-N-(3-pyrrolidin-1-yl-propyl)-propionamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4477 - 4492

8
[ 24455-93-4 ]
[ 169555-95-7 ]
[ 99-04-7 ]
(S)-N-{1-[2-(4-methoxyphenylamino)ethylcarbamoyl]-2-pyridin-4-ylethyl}-3-methylbenzamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4979 - 4984

9
[ 71989-31-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 169555-95-7 ]
(S)-2-({(S)-1-[(S)-2-((2S,3R)-2-Acetylamino-3-hydroxy-butyrylamino)-3-pyridin-4-yl-propionyl]-pyrrolidine-2-carbonyl}-amino)-succinamide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 2216 - 2217

10
PVC-EDA [ No CAS ]
[ 169555-95-7 ]
C₂₅H₂₅N₄O₃Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; diisopropyl-carbodiimide; In DMF (N,N-dimethyl-formamide); for 16h;	Solid-Phase Synthesis of Compound 135 (Scheme AC) L-Alaninamide, 4-chloro-N-[[[1-[(2,6-dichlorophenyl)methyl]-3-(1-pyrrolidinylmethyl)-1H-indol-6-yl]amino]carbonyl]-L-phenylalanyl-N-(2-aminoethyl)-3-(4-pyridinyl)-(Compound 135) [0150] 2-Chlorotrityl chloride resin (4.8 g, 8.65 mmol; Advanced ChemTech) was stirred in DMF (100 mL) as ethylene diamine AC1 (15.6 g, 260 mmol) was added, the reaction was stirred at about rt for about 16 h. The resin AC2 was filtered on a sintered glass funnel and washed with DMF (4), MeOH (3) and DCM (3), then dried in vacuo. A portion of resin AC2 (2.0 g, 3.5 mmol) was placed in a solid phase hour-glass reactor and agitated (nitrogen bubbling) in DMF (40 mL) with Fmoc-4-pyridyl alanine (3.9 g, 10 mmol), HOBT (1.53 g, 10 mmol) and DIC (1.26 g, 10 mmol) for about 16 h. The solution was drawn off and the resin was washed with DMF (4), DCM (4) and DMF (2) and then combined with 20% piperidine in DMF (25 mL) and agitated for about 1.5 h. The solution was drained and the resin AC3 was washed with DMF (5) then agitated in DMF (20 mL) with Fmoc-4-Chlorophenyl alanine (4.22 g, 10 mmol), HOBT (1.53 g, 10 mmol) and DIC (1.26 g, 10 mmol) at about rt for about 16 h. The solution was removed and the resin was washed with DMF (5), MeOH (3), DCM (3) and DMF (2), then combined with 20% piperidine in DMF (25 mL) and agitated for about 1 h. The solution was drained and the resin was washed with DMF (4), DCM (4) and dry DCM (3) and stored in vacuo to give AC4. To 4-Nitrophenyl chloroformate (2.02 g, 10 mmol) in dry DCM (200 mL) at about -20 C., a solution of AA2b (3.6 g, 12.5 mmol) and DIEA (2.58 g, 20 mmol) in DCM (50 mL) was added over about 10 min and stirred at about -20 C. for about 20 min. The dipeptidyl resin (1.5 g, 2.5 mmol) was added and stirred at about -20 C. for about 25 min. and then at about rt for about 16 h. The resin AC5 was filtered and washed with DMF (3), MeOH (3) and DCM (4), then dried in vacuo. Pyrrolidine (8.9 g, 125 mmol) was added to 1,4-dioxane:glacial acetic acid (4:1; 240 mL) and, at about rt, formaldehyde (37%, 8.11 g, 100 mmol) was added; the solution was then stirred under argon for about 15 min; the resin AC5 from above was added and stirred for about 16 h. The resin was filtered and washed with DMF (4), MeOH (4), DCM (2) and MeOH (3), then dried in vacuo at about rt for about 72 h. The dried resin was combined with TFA:DCM:anisole (30:70:0.50, 50 mL) and stirred at about rt for about 1 h. The resin was filtered and washed with fresh 30% TFA in DCM; the filtrates were combined and evaporated in vacuo to an oil, which was triturated with diethyl ether (3) to give the crude product Compound 135 as a white solid. Purification was accomplished via reverse-phase HPLC using 0.16% TFA in ACN:0.20% TFA in water (33:67) and upon lyophilization afforded a white floccular solid. The solid was dissolved in 1N HCl (25 mL) and evaporated in vacuo to a solid; this procedure was repeated twice. The solid was then dissolved in 1N HCl (25 mL), frozen and lyophilized to give Compound 135 as a white floccular solid. 1H NMR (CD3OD) delta 8.55 (d, J=8.0, 2H), 7.82-7.05 (m, 13H), 5.58 (s, 2H), 4.70 (m, 1H), 4.45 (m, 3H), 3.55-2.90 (m, 12H), 2.20-1.90 (m, 4H). ES-MS m/z 789 (MH+). Anal. calcd. for C40H43Cl3N8O3.3.0 HCl 4.75H2O (790.19/985.22): C, 48.76; H, 5.68; N, 11.37; Cl, 21.60; H2O, 8.68. Found: C, 48.41; H, 5.41; N, 11.37; Cl, 21.87; H2O, 7.52.

Reference： [1]Patent: US2003/224999,2003,A1 .Location in patent: Page 16; 24

11
C₉₂H₁₁₁ClN₉O₁₃PolS [ No CAS ]
[ 169555-95-7 ]
C₁₁₅H₁₂₉ClN₁₁O₁₆PolS [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 3302 - 3307

12
[ 103-72-0 ]
[ 96-32-2 ]
[ 169555-95-7 ]
[ 134-96-3 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
[ 1082954-00-4 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 7065 - 7074

13
Fmoc-Tyr(Clt)-OH [ No CAS ]
C₄₁H₄₉N₂O₇PolS [ No CAS ]
[ 169555-95-7 ]
C₆₂H₆₉ClN₅O₈PolS [ No CAS ]

Reference： [1]Molecules,2010,vol. 15,p. 1590 - 1631

14
C₄₁H₄₉N₂O₇PolS [ No CAS ]
[ 35661-39-3 ]
[ 169555-95-7 ]
C₃₇H₅₂N₅O₇PolS [ No CAS ]

Reference： [1]Molecules,2010,vol. 15,p. 1590 - 1631

15
C₄₁H₄₉N₂O₇PolS [ No CAS ]
[ 35661-40-6 ]
[ 169555-95-7 ]
C₄₃H₅₆N₅O₇PolS [ No CAS ]

Reference： [1]Molecules,2010,vol. 15,p. 1590 - 1631

16
[ 29022-11-5 ]
[ 108-24-7 ]
[ 101555-63-9 ]
[ 169555-95-7 ]
(2R)-2-[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-(4-nitrophenyl)propionic acid [ No CAS ]
[ 1233962-33-8 ]

Reference： [1]Angewandte Chemie - International Edition,2010,vol. 49,p. 3473 - 3476

17
[ 29022-11-5 ]
[ 108-24-7 ]
[ 169555-95-7 ]
(2R)-2-[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-(4-nitrophenyl)propionic acid [ No CAS ]
[ 136552-06-2 ]
[ 1233962-41-8 ]

Reference： [1]Angewandte Chemie - International Edition,2010,vol. 49,p. 3473 - 3476

18
C₄₀H₆₃N₂O₂PolSi [ No CAS ]
[ 169555-95-7 ]
C₆₃H₈₁N₄O₅PolSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To the resin 13 (560 mg) in DMF (2.5 mL) were added a solutionof the appropriate Fmoc-protected amino acid (see Tables 1-3)(0.3 M), PyBOP (0.3 M) and HOBt (0.3 M) in dry DMF (4.2 mL). Thesuspensions were stirred for 3 min and then DIPEA (0.6 M) wasadded. The suspensions were stirred for 3 h under an argon atmosphereat rt. The resins were washed successively with DCM(150 mL), MeOH (120 mL), DCM (75 mL) and dried overnight undervacuum to give resins 14, each bearing an appropriate Fmoc-protectedamino acid. To the resins 14 (161 mg, 0.13 mmol) wereadded a solution of piperidine (20%, v/v) in DCM (2.1 mL) and themixtures were stirred for 1 h at rt. After filtration, the resins werewashed successively with DCM (50 mL), MeOH (45 mL), DCM(25 mL) and dried under vacuum to give resins 15. Portions(65 mg) of resins 15 were placed in reactor wells (12 mL) of anautomated synthesizer reaction block (40-well format) (AdvancedChemTech). To each well was added a solution of appropriate carboxylicacid (see Tables 1-3) (0.3 M), PyBOP (0.3 M) and HOBt 6-Cl(0.3 M) and DIPEA (0.6 M) in dry DMF (2 mL). The suspensionswere vortexed at 300 rpm over a period of 5 h under an argonatmosphere. The wells were then filtered to remove the reactivesolution from the resins 16 and washed successively with THF,DCM, MeOH and DCM.

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 347 - 351
[2]Steroids,2016,vol. 107,p. 55 - 64

19
[ 102913-23-5 ]
[ 1397815-20-1 ]
[ 169555-95-7 ]

Reference： [1]Amino Acids,2012,vol. 42,p. 1339 - 1348

20
[ 872-85-5 ]
[ 1397815-20-1 ]
[ 169555-95-7 ]

Reference： [1]Amino Acids,2012,vol. 42,p. 1339 - 1348

21
[ 746672-87-7 ]
[ 1397815-20-1 ]
[ 169555-95-7 ]

Reference： [1]Amino Acids,2012,vol. 42,p. 1339 - 1348

22
[ 1397697-82-3 ]
[ 1397815-20-1 ]
[ 169555-95-7 ]

Reference： [1]Amino Acids,2012,vol. 42,p. 1339 - 1348

23
(Z)-2-acetamido-3-(pyridin-4-yl) acrylic acid [ No CAS ]
[ 1397815-20-1 ]
[ 169555-95-7 ]

Reference： [1]Amino Acids,2012,vol. 42,p. 1339 - 1348

24
[ 111759-54-7 ]
[ 1397815-20-1 ]
[ 169555-95-7 ]

Reference： [1]Amino Acids,2012,vol. 42,p. 1339 - 1348

25
[ 1956-21-4 ]
[ 1397815-20-1 ]
[ 169555-95-7 ]

Reference： [1]Amino Acids,2012,vol. 42,p. 1339 - 1348

26
[ 56-45-1 ]
[ 29022-11-5 ]
[ 35661-60-0 ]
C₂₂H₂₆N₂O₃ [ No CAS ]
[ 71989-31-6 ]
[ 91000-69-0 ]
[ 77284-32-3 ]
[ 109425-56-1 ]
[ 116611-64-4 ]
[ 169555-95-7 ]
PyrRPRLSHKGPNleP(4-pyridyl)Ala [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 2431 - 2440

27
2-chlorotrityl chloride polystyrene resin [ No CAS ]
[ 169555-95-7 ]
C₄₂H₃₂ClN₂O₄Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 25℃; for 1h;	General procedure: Each 2-chlorotrityl chloride resin (100 mg, 1.6 mmol/g) was placed in a 5 mL polypropylene syringe fitted with a polyethylene filter disc. Each resin was washed with CH2Cl2 (2 mL, 1 h), and a solution of the corresponding Fmoc-amino acid 3a-mm (0.16 mmol) and iPr2NEt (109 muL, 0.64 mmol) in CH2Cl2 (2 mL) were then added. Each mixture was agitated for 1 h at 25 C. Solvents and soluble reagents were removed by suction. All resins were subjected to the following washing treatments with CH2Cl2-MeOH-iPr2NEt (17:2:1, 2 mL × 3), DMF (2 mL × 3), and CH2Cl2 (2 mL × 3).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 4872 - 4877

28
[ 198544-94-4 ]
D-6-methyl-8β-ergolinylmethylthioacetyl acid [ No CAS ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 154524-72-8 ]
1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan [ No CAS ]
[ 169555-95-7 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
C₁₁₇H₁₅₈N₁₈O₁₈S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The peptide moiety of Compound 4 was automatically synthesized on an Applied Biosystems (Foster City, Calif., USA) model 433A peptide synthesizer based on Fmoc chemistry. Pre-loaded Fmoc-Phe-2ClTrt resin with substitution of 0.58 mmol/g was used and synthesis was carried out on a 0.2 mmol scale. The Fmoc amino acid cartridges were obtained from AnaSpec (San Jose, Calif., USA). The Fmoc amino acids with the side chain protections were as follows: Fmoc-Thr(tBu)-OH, Fmoc-Lys(Boc)-OH, Fmoc-DTrp(Boc)-OH, Fmoc-Arg(Pbf)-OH, <strong>[198544-94-4]Fmoc-DLys(Mtt)-OH</strong>, and Fmoc-4Pal (Chem-Impex Inc.; Wood Dale, Ill., USA). The synthesis was carried out on a 0.25 mmol scale. The ABI 433A peptide synthesizer was programmed to perform the following reaction cycle: washing with NMP; removing Fmoc protecting group with 20% piperidine in NMP for 10 minutes; washing with NMP; and coupling with pre-activated amino acid for 1 hour. The resin was double coupled successively according to the sequence until peptide chain assembly was finished. During washing and removing of Fmoc cycles, the Fmoc amino acid (4 eq., 1 mmol) was first pre-activated with 2 mL of a solution of 0.45M HBTU/HOBt in DMF. This activated amino acid ester, 1 mL of 2M DIEA and 2.5 mL of NMP were added to the resin. Before aminoalkylation, the resin was treated with 25% piperidine in DMF for 40 minutes and washed with DMF, MeOH and DCM. 5 mmol of Fmoc-Tyr(tBu)-OH in DCM was reacted with 5.1 mmol of N,O-dimethylhydroxylamine hydrochloride, PyBOP and DIEA to convert to a Weinreb amide. Then 1 mmol of it was dissolved in 10 mL of anhydrous THF and cooled down in a salt-ice bath (-5 C.) for 15 minutes, to which 1 mmol of LAH (1 mL) was slowly dropped in 20 minutes. The reaction was kept cold in an ice bath (0 C.) and stirred for additional 1 hour. The reaction was quenched by addition of 10 mL of 10% KHSO4 and diluted with 50 mL of DCM. The aqueous solution was further extracted with DCM (50 mL, 30 mL, and 20 mL). All organic layers were washed with 10% KHSO4 (20 mL×3) and brine (20 mL×3). After drying over Na2SO4, it was evaporated to dryness. HPLC showed a broad peak. This crude aldehyde (Fmoc-Tyr(tBu)-CHO) was dissolved in 2.5 mL of DMF and mixed with the N-terminal free resin in a solution of 10 mL of DMF and 125 muL of AcOH, to which 2.1 mmol (136.8 mg) of NaBH3CN was added in 5 portions in half hour increments. The reaction was shaken overnight. An aliquot of resin was cleaved, and the reaction was confirmed to be complete. After washing, the resin was treated with MeOH for 2 hours, and then mixed with 25% piperidine/DMF overnight and the resin was washed successively with DMF, MeOH and DCM, and then coupled with D-6-methyl-8beta-ergolinylmethylthioacetyl acid (3 eq.), PyAOP (5 eq.) and DIEA (10 eq.) overnight. The cleavage of an aliquot showed the coupling was complete. After washing with DCM, the resin was treated with 32 mL of a solution (for 0.159 mmol scale resin) containing TFA/DCM (1:99) for 30 minutes, then filtered into 0.583 mL of TEA and evaporated to dryness. This process was repeated three more times. The crude linear product was dissolved in 77.5 mL of DCM, to which 2 eq. of PyAOP, 2.5 eq. of HOBt and 16 eq. of DIEA were added. The lactam formation was monitored by HPLC.

Reference： [1]Patent: US2015/290330,2015,A1 .Location in patent: Paragraph 0324-0328

29
[ 13734-34-4 ]
[ 862847-44-7 ]
[ 71989-38-3 ]
[ 71989-35-0 ]
1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan [ No CAS ]
[ 169555-95-7 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
NH₂-cyclo[DLys-Arg-Phe-4Pal-DTrp-Lys(ivDde)-Thr-Tyr] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29.8%		Fmoc-Tyr(tBu)-OH (12 mmole, 5.51 g) was dissolved in solution of 40 mL of DCM and 20 mL of DMF. To this solution, 2-chlorotrityl resin with substitution of 1.5 mmol/g (12.135 mmole, 8.09 g) and diisopropylethylamine (36 mmol, 6.27 mL) were added. After 3 hours, the resin was filtered and washed 3 times with DMF and then DCM. The resin was then treated for 1.5 hours with 10% DIEA in MeOH. The resin was sequentially washed with DMF, DCM and MeOH and dried overnight. Substitution of the resin was determined as 0.58 mmoles/g according to 1,8-diazabicyclo[5.4.0]undec-7-ene procedure in M. Gude, et al., Lett. Pep. Sci. 9, 203. (2003). The titled peptide was prepared using Symphony synthesizer (Protein Technologies, Inc., Tucson, Ariz., USA) based on Fmoc chemistry. 0.345 g of pre-loaded Fmoc-Tyr(tBu)-2-ClTrt resin with substitution of 0.58 mmol/g was used and synthesis was carried out on a 0.2 mmol scale. The Fmoc amino acids utilized with side chain protecting groups were as follows: Fmoc-Thr(tBu)-OH, Fmoc-Lys(ivDde)-OH, Fmoc-DTrp(Boc)-OH, Fmoc-Phe-OH, <strong>[169555-95-7]Fmoc-4Pal-OH</strong>, and Fmoc-Arg(Pbf)-OH (CBL Biopharma, Boulder, Colo., USA) and Fmoc-DLys (Mtt)-OH (Chem-Impex Int'l Inc., Wood Dale, Ill., USA). The synthesizer was programmed to perform the following reaction cycles: washing with DMF; removing Fmoc protecting group with 20% piperidine in DMF for 15 minutes for the first 3 amino acids and 30 minutes for the Fmoc-DTrp(Boc)-OH through the end of the peptide; washing with DMF; and coupling with 0.9 eq. of HCTU. The resin was double coupled successively according to the sequence until peptide chain assembly was finished. The synthesis was programmed to carry out a final deprotection to remove Fmoc. The resin was mixed with 12 eq. excess of (Boc)2O and 6 eq. of DIEA in 4 mL of DMF for 2 hours, which was repeated once. An aliquot of global cleavage showed MS of 1383, which was in agreement with the calculated molecular weight of 1382.6. UPLC (5% to 80% B in 5 min, where A was 0.1% TFA in water and B was 0.1% TFA in acetonitrile) showed product of Rt=2.82. The above Boc-DLys(Mtt)-Arg(Pbf)-Phe-4Pal-DTrp(Boc)-Lys(ivDde)-Thr(tBu)-Tyr(tBu)-2-Cart resin was treated with 25 mL of cold TFA/TIS/DCM (1/5/94) for 30 minutes to afford selective cleavage. The filtrate DCM cleavage solution was neutralized by addition of 0.47 mL of TEA while in an ice bath. This was repeated twice, then three neutralized filtrates were combined and cyclization was immediately carried out using 5 eq. of PyBOP, 8 eq, of DIEA and a catalytic amount of DMF overnight. The UPLC analysis showed the retention time was shifted from 2.83 to 3.946 (gradient was 50% to 100% Buffer B in 5 minutes). MS showed 1929 (linear is 1947). The mixture was evaporated to dryness and taken into 20 mL of water and triturated to obtain an oily precipitate. The residue was mixed with 12 mL of TEA solution containing 0.8 mL of TIS, 0.8 mL of water and 0.65 g of DTT for 4 hr. The mixture was poured into 80 mL of ether and centrifuged to get precipitate. The crude cyclized peptide was dissolved in 5 mL of 50% AcOH in water and diluted 10 fold with 0.1% TFA in water. A small amount of ACN was added to make the solution clear if needed. It was loaded onto a reversed-phase preparative Luna C18 column from Phenomenex (100×21.2 mm, 100 , 5 mum). The peptide was eluted with a gradient from 20-50% B in 50 minutes, where A was 0.1% TFA in water and B was 0.1% TFA in acetonitrile. The fractions were checked on an Acquity UPLC (Waters) and fractions containing pure product were combined and lyophilized to dryness. ESI-MS analysis showed the correct product with 1365.2, in agreement with the calculated molecular weight of 1365. It generated 96 mg with 95% purity. The average yield was 29.8% based on the starting resin.

Reference： [1]Patent: US2015/290330,2015,A1 .Location in patent: Paragraph 0337-0339

30
H-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg-(Pbf)-Cha-Rink Amide resin [ No CAS ]
[ 108-24-7 ]
[ 132388-59-1 ]
[ 66-25-1 ]
Fmoc-Ser(OtBu)-OH [ No CAS ]
[ 94744-50-0 ]
[ 71989-31-6 ]
[ 135673-97-1 ]
[ 169555-95-7 ]
(S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
Ac-Ser-D-Pro-Arg-Pya⁽⁴⁾-Cha-Aib-Asn-Lys(Hexyl)-Aib-Thr-Arg-Gln-Arg-Cha-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.7 mg		[Example 25] (Synthesis method Y): Production of Ac-[D-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys (Hexyl)30]-PYY(23-36) (compound No. 279) Synthesis of Ac- [D-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys(Hexyl)30]-PYY(23-36) (0322) H-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Rink Amide resin (89.7 mg, 0.02 mmol) synthesized in Example 23 was weighed and placed in a reaction vessel, washed with DMF and, after swelling, treated with Fmoc-Lys(Mtt)-OH (125.0 mg, 0.2 mmol), 0.5 M HOAt/DMF solution (0.4 mL, 0.2 mmol), DIPCDI (31.8 muL, 0.2 mmol) for 15 hr to introduce Lys(Mtt) residue. The obtained resin was washed with toluene, treated with TFA-triisopropylsilane-trifluoroethanol-toluene (1:5:47:47) for 10 min, and an operation to remove the reaction solution was repeated until the solution was no longer colored. The resin was washed with toluene, neutralized by washing with 5% DIEA-toluene solution, and washed with DMF. The obtained resin was suspended in DMF, 1-hexanal (2.5 muL, 0.04 mmol) was added in the presence of acetic acid (50 muL) and the mixture was stirred for 15 min. NaBH3CN (6.2 mg, 0.1 mmol) was added, and the mixture was further stirred for 1.5 hr. The resin was washed with DMF, and treated with Boc2O (24.4 mg, 0.2 mmol), DIEA (34.8 muL, 0.2 mmol) in DMF at room temperature for 3 hr. The progress of the reaction was confirmed by Kaiser test, and Asn(Trt), Aib, Cha, Pya(4), Arg(Pbf), D-Pro, Ser(But) were successively introduced by manual solid phase synthesis process including repeats of removal of Fmoc by 20% piperidine/DMF treatment and condensation by a treatment with Fmoc-amino acid (0.1 mmol), 0.5 M HOAt/DMF (0.2 mL, 0.1 mmol), DIPCDI (16 muL, 0.1 mmol). Then, after removal of Fmoc, the resin was treated with Ac2O (9.4 muL), DIEA (17.4 muL) in DMF for 30 min for acetylation, and the obtained resin was washed with MeOH and dried. (0323) The obtained resin (103.9 mg) was treated with TFA: thioanisole: m-cresol: HO: EDT: TIS (80:5:5:5:2.5:2.5) (1 mL) for 90 min, an operation to add diethyl ether to the reaction solution, precipitate a white powder by centrifugation, and remove diethyl ether by decantation was repeated twice. The residue was dissolved in aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and purified by preparative HPLC using Daisopak-SP100-5-ODS-P 2×25 cm, and Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, flow rate 8 mL/min, A/B: 73/27-63/37 linear density gradient elution (60 min) was performed. The eluted object product was fractionated in test tubes, and each fraction was analyzed by HPLC to specify fractions containing only the object product. They were combined and freeze-dried to give 2.7 mg of a white powder. MALDI-TOF-MS analysis, (M+H)1891.9 (Calculated 1892.2) HPLC elution time: 9.6 min elution condition (HPLC mode d): column: Merck Chromolith Performance RP-18e(4.6×100 mm I.D.) eluent: using Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, A/B: 80/20 - 30/70 linear concentration gradient elution (25 min) flow rat: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0322-0323

31
H-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg-(Pbf)-Cha-Rink Amide resin [ No CAS ]
[ 108-24-7 ]
[ 132388-59-1 ]
Fmoc-Ser(OtBu)-OH [ No CAS ]
[ 94744-50-0 ]
[ 71989-31-6 ]
[ 152120-54-2 ]
[ 135673-97-1 ]
[ 169555-95-7 ]
(S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
Ac-Ser-D-Pro-Arg-Pya⁽⁴⁾-Cha-Aib-Asn-Har-Aib-Thr-Arg-Gln-Arg-Cha-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4.1 mg		The obtained resin (89.7 mg, 0.02 mmol) was weighed and placed in a reaction vessel, washed with DMF and, after swelling, treated with Fmoc-Lys(Mtt)-OH (125.0 mg, 0.2 mmol), 0.5 M HOAt/DMF solution (0.4 mL, 0.2 mmol), DIPCDI (31.8 muL, 0.2 mmol) for 15 hr to introduce Lys(Mtt) residue. The obtained resin was washed with toluene, treated with TFA-triisopropylsilane-trifluoroethanol-toluene (1:5:47:47) for 10 min, and an operation to remove the reaction solution was repeated until the solution was no longer colored. The resin was washed with toluene, neutralized by washing with 5% DIEA-toluene solution, washed again with toluene. To the obtained resin was added N,N-bis-Boc-1-guanylpyrazole (31.0 mg, 0.1 mmol), DIEA (17.4 muL, 0.1 mmol), in toluene:TFE (3:1), and treated at room temperature overnight. The progress of the reaction was confirmed by Kaiser test, and Asn(Trt), Aib, Cha, Pya(4), Arg(Pbf), D-Pro, Ser(Bu) were successively introduced by manual solid phase synthesis process including repeats of removal of Fmoc by 20% piperidine/DMF treatment and condensation by a treatment with Fmoc-amino acid (0.1 mmol), 0.5 M HOAt/DMF (0.2 mL, 0.1 mmol), DIPCDI (16 muL, 0.1 mmol). Then, after removal of Fmoc, the resin was treated with AcO (9.4 muL), DIEA (17.4 muL) in DMF for 30 min for acetylation, and the obtained resin was washed with MeOH and dried. The obtained resin (87.1 mg) was treated with TFA: thioanisole: m-cresol: HO: EDT: TIS (80:5:5:5:2.5:2.5) (1 mL) for 90 min, an operation to add diethyl ether to the reaction solution, precipitate a white powder by centrifugation, and remove ether by decantation was repeated twice. The residue was dissolved in aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and purified by preparative HPLC using Daisopak-SP100-5-ODS-P 2×25 cm, and Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, flow rate 8 mL/min, A/B: 78/22-68/32 linear concentration gradient elution (60 min) was performed. The eluted object product was fractionated in test tubes, and each fraction was analyzed by HPLC to specify fractions containing only the object product. They were combined and freeze-dried to give 4.1 mg of a white powder. MALDI-TOF-MS analysis, (M+H)1850.3 (Calculated 1850.1) HPLC elution time: 7.4 min elution condition (HPLC mode d): column: Merck Chromolith Performance RP-18e(4.6×100 mm I.D.) eluent: using Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, A/B: 80/20 - 30/70 linear concentration gradient elution (25 min) flow rate: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0320

32
H-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg-(Pbf)-Cha-Rink Amide resin [ No CAS ]
[ 108-24-7 ]
Fmoc-Ser(OtBu)-OH [ No CAS ]
[ 94744-50-0 ]
[ 71989-31-6 ]
[ 88574-06-5 ]
[ 135673-97-1 ]
[ 169555-95-7 ]
(S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
Ac-Ser-D-Pro-Arg-Pya⁽⁴⁾-Cha-Aib-Asn-Lys(Ac)-Aib-Thr-Arg-Gln-Arg-Cha-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5.1 mg		[Example 24] (Synthesis method X): Production of Ac-[D-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys(Ac)30]-PYY(23-36) (compound No. 278) Synthesis of Ac-[D-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys(Ac)30]-PYY (23-36) (0321) H-Aib-Thr (But) -Arg (Pbf) -Gln(Trt)-Arg(Pbf)-Cha-Rink Amide resin (89.7 mg, 0.02 mmol) synthesized in Example 23 was weighed and placed in a reaction vessel, washed with DMF and, after swelling, treated with Fmoc-Lys(Mtt)-OH (125.0 mg, 0.2 mmol), 0.5 M HOAt/DMF solution (0.4 mL, 0.2 mmol), DIPCDI (31.8 muL, 0.2 mmol) for 15 hr to introduce Lys(Mtt) residue. The obtained resin was washed with toluene, treated with TFA-triisopropylsilane-trifluoroethanol-toluene (1:5:47:47) for 10 min, and an operation to remove the reaction solution was repeated until the solution was no longer colored. The resin was washed with toluene, neutralized by washing with 5% DIEA-toluene solution, washed with DMF, and the obtained resin was treated overnight with AcO (9.4 muL), DIEA (17.4 muL) in DMF at room temperature. The progress of the reaction was confirmed by Kaiser test, and Asn(Trt), Aib, Cha, Pya(4), Arg(Pbf), D-Pro, Ser(Bu) were successively introduced by manual solid phase synthesis process including repeats of removal of Fmoc by 20% piperidine/DMF treatment and condensation by a treatment with Fmoc-amino acid (0.1 mmol), 0.5 M HOAt/DMF (0.2 mL, 0.1 mmol), DIPCDI (16 muL, 0.1 mmol). Then, after removal of Fmoc, the resin was treated with AcO (9.4 muL), DIEA (17.4 muL) in DMF for 30 min for acetylation, and the obtained resin was washed with MeOH and dried. The obtained resin (102.8 mg) was treated with TFA: thioanisole: m-cresol: HO: EDT: TIS (80:5:5:5:2.5:2.5) (1 mL) for 90 min, an operation to add diethyl ether to the reaction solution, precipitate a white powder by centrifugation and remove ether by decantation was repeated twice. The residue was dissolved in aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and purified by preparative HPLC using Daisopak-SP100-5-ODS-P 2×25 cm, and Solution A: 0.1% TFA-water, Solution B:. 0.1% TFA-containing acetonitrile, flow rate 8 mL/min, A/B: 77/23-67/33 linear concentration gradient elution (60 min) was performed. The eluted object product was fractionated in test tubes, and each fraction was analyzed by HPLC to specify fractions containing only the object product. They were combined and freeze-dried to give 5.1 mg of a white powder. MALDI-TOF-MS analysis, (M+H)1850.2 (Calculated 1850.1) HPLC elution time: 8.0 min elution condition (HPLC mode d): column: Merck Chromolith Performance RP-18e(4.6×100 mm I.D.) eluent: using Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, A/B: 80/20 - 30/70 linear concentration gradient elution (25 min) flow rate: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0321

33
[ 38041-19-9 ]
H-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin [ No CAS ]
Fmoc-Ser(OtBu)-OH [ No CAS ]
[ 94744-50-0 ]
[ 71989-31-6 ]
[ 530-62-1 ]
[ 135673-97-1 ]
[ 169555-95-7 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
tetrahydro-2H-pyran-4-yl-carbamoyl-[D-Pro₂₄,Pya⁽⁴⁾26,Cha₂₇,36,Aib₂₈,31,Lys₃₀]-PYY(23-36) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
515 mg		Synthesis of tetrahydro-2H-pyran-4-ylcarbamoyl-[D-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys30]-PYY(23-36) (0317) H-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin (0.289 mmol/g, 1.73 g, 0.5 mmol) obtained by condensing amino acids in the same manner as in Example 12 and using Sieber Amide resin as a starting material, ABI433A peptide synthesizer DCC/HOBt 0.25 mmol protocol was swollen with DMF. Then, the resin was treated with Fmoc-Aib-OH (651 mg, 2.0 mmol), HOAt in DMF (0.5 M, 4.0 mL, 2.0 mmol), DIPCDI (318 muL, 2.0 mmol) for 1.5 hr. Fmoc group was removed with 20% piperidine in DMF, and the resin was treated with Fmoc-Cha-OH (787 mg, 2.0 mmol), HOAt in DMF (0.5 M, 4.0 mL, 2.0 mmol), DIPCDI (318 muL, 2.0 mmol) for 1.5 hr. The resin was washed, and further treated overnight with Fmoc-Cha-OH (787 mg, 2.0 mmol), HOAt in DMF (0.5 M, 4.0 mL, 2.0 mmol), DIPCDI (318 muL, 2.0 mmol). The resin was washed, and subjected to a capping treatment with decanoic anhydride (737 muL, 2. 0 mmol), DIEA (348 muL, 2.0 mmol) in DMF for 30 min. Fmoc group was removed with 20% piperidine in DMF, and the resin was treated with Fmoc-Pya(4)-OH (767 mg, 2.0 mmol), HOAt in DMF (0.5 M, 4.0 mL, 2.0 mmol), DIEA (348 muL, 2.0 mmol), DIPCDI (318 muL, 2.0 mmol) for 2.5 hr. The resin was washed with DMF, Fmoc group was removed with 20% piperidine in DMF, and the resin was treated with Fmoc-Arg(Pbf)-OH (1.30 g, 2.0 mmol), HOAt in DMF (0.5 M, 4.0 mL, 2.0 mmol), DIPCDI (318 muL, 2.0 mmol) for 2 hr. The resin was washed, and subjected to a capping treatment with decanoic anhydride (737 muL, 2.0 mmol), DIEA (348 muL, 2.0 mmol) in DMF for 30 min. Fmoc group was removed with 20% piperidine in DMF, and the resin was treated with Fmoc-D-Pro-OH (674 mg, 2.0 mmol), HOAt in DMF (0.5 M, 4.0 mL, 2.0 mmol), DIPCDI (318 muL, 2.0 mmol) for 12 hr. The resin was washed, and further treated overnight with Fmoc-D-Pro-OH (674 mg, 2.0 mmol), HOAt in DMF (0.5 M, 4.0 mL, 2.0 mmol), DIPCDI (318 muL, 2.0 mmol). The resin was washed, and subjected to a capping treatment with decanoic anhydride (737 muL, 2.0 mmol), DIEA (348 muL, 2.0 mmol) in DMF for 30 min. The resin was washed with DMF, Fmoc group was removed with 20% piperidine in DMF, and the resin was treated with Fmoc-Ser(But)-OH (767 mg, 2.0 mmol), HOAt in DMF (0.5 M, 4.0 mL, 2.0 mmol), DIPCDI (318 muL, 2.0 mmol) for 2 hr. The resin was washed successively with DMF, MeOH, and dried under reduced pressure. The total amount of the obtained H-Ser(But)-D-Pro-Arg(Pbf)-Pya(4)-Cha-Aib-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin was swollen again with DMF, and treated with CDI (405 mg, 2.5 mmol), DIEA (436 muL, 2.5 mmol) in DMF for 2 hr. The resin was washed with DMF, and treated overnight with 4-aminotetrahydropyrane (404 mg, 4.0 mmol) in DMF. The resin was washed successively with DMF, MeOH, dried under reduced pressure and the total amount of the obtained resin was suspended in TFA: thioanisole: m-cresol: H2O: EDT: TIS (80:5:5:5:2.5:2.5) (15 mL), and the mixture was stirred at room temperature for 4 hr. The reaction solution was added to stirring diethyl ether under ice-cooling while removing the resin by a filter to obtain precipitation, and an operation to remove the supernatant after centrifugation was repeated 3 times. The residue was extracted with 50% aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and purified in 9 portions by HPLC. The HPLC conditions were YMC Pack R&D-ODS-5-B S-5 120A column (30x250 mm), Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, flow rate 15 mL/min, A/B: 77/23-67/33 linear concentration gradient elution (60 min). Each fraction was analyzed by HPLC to specify fractions containing only the object product. The fractions with low purity obtained by the first purification were concentrated, and subjected to HPLC separation in 2 portions under the same conditions. All the fractions containing only the object product were combined and freeze-dried to give 685 mg of a white powder. The obtained purified sample (685 mg) was dissolved in CHCN/HO (15/30 mL), and AG 1x8 AcO resin (7.54 mL, 9.05 mmol equivalents) was added. The solution was stood for 1 hr while occasionally stirring with hand, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, concentrated in an evaporator to reduce the liquid amount to about 5 mL, and the solution was freeze-dried to give 515 mg of a white powder. MALDI-TOF-MS analysis, (M+H)1893.2 (Calculated 1893.1) HPLC elution time: 7.5 min elution condition (HPLC mode g): column: SHISEIDO CAPCELL PAK C18 MGII(4.6×100 mm) eluent: using Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, A/B: 80/20 - 30/70 linear concentration gradient elution (25 min) flow rate: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0317-0318

34
[ 38041-19-9 ]
Cha-Aib-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin [ No CAS ]
[ 71989-18-9 ]
[ 71989-31-6 ]
[ 530-62-1 ]
[ 169555-95-7 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
(tetrahydro-2H-pyran-4-yl)carbamoyl-[Glu₂₃,D-Pro₂₄,Pya⁽⁴⁾26,Cha₂₇,36,Aib₂₈,31,Lys₃₀]-PYY(23-36) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
173 mg		[Example 26] (0324) (Synthesis method Z): Production of (Tetrahydro-2H-pyran-4-yl)carbamoyl-[Glu23,D-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys30]-PYY(23-36) (compound No. 282) Compound No. 282: (0325) Synthesis of (Tetrahydro-2H-pyran-4-yl)carbamoyl-[Glu23,D-Pro24, Pya(4)26, Cha27,36,Aib28,31, Lys30]-PYY(23-36) (0326) Cha-Aib-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin (SEQ ID NO:179)(0.375 mmol) obtained by condensing amino acids in the same manner as in Example 12 and using commercially available Sieber Amide resin as a starting material, and ABI433A peptide synthesizer DCC/HOBt 0.25 mmol protocol was weighed and placed in a reaction vessel, washed with DMF, and stirred in DMF for 20 min to swell the resin. Then, the resin was treated with Fmoc-Pya(4)-OH (1165.3 mg, 3 mmol), 0.5 M HOAt/DMF solution (3 mL, 4 mmol), DIPCDI (0.477 mL, 3 mmol) for 75 min to introduce Pya(4) residue. In this case, DIEA (0.5226 mL, 3 mmol) was added to the reaction solution during condensation. The N-terminal Fmoc group was removed by 20% piperidine/DMF treatment. By a similar procedure, Arg(Pbf) was introduced. In the same manner, removal of Fmoc group and condensation were repeated to introduce D-Pro, Glu(OBut), and the obtained resin was washed with MeOH and dried to give H-Glu(OBut)-D-Pro-Arg(Pbf)-Pya(4)-Cha-Aib-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-NH-Sieber Amide resin. The obtained resin was washed with DMF and, after swelling, treated with CDI (304.0 mg, 1.88 mmol), DIEA (0.327 mL, 1.88 mmol), DMF (3 mL) for 60 min. The resin was washed, and further treated for 60 min under similar conditions. The resin was washed with DMF, treated with 4-aminotetrahydropyrane (303.0 mg, 3 mmol), DMF (3 mL) for 4 hr, and washed successively with DMF, MeOH and dried. The obtained resin (1.63 g) was treated with TFA: thioanisole: m-cresol: H2O: EDT: TIS (80:5:5:5:2.5:2.5) (20 mL) for 4 hr, an operation to add diethyl ether to the reaction solution, precipitate a white powder by centrifugation, and remove ether by decantation was repeated twice. The residue was dissolved in aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and concentrated in an evaporator. After confirmation of the purity of the obtained crude peptide solution by HPLC, it was purified in 10 portions by preparative HPLC using Daisopak-SP100-5-ODS-P 2×25 cm (Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, flow rate 8 mL/min, A/B: 80/20-70/30 linear concentration gradient elution (60 min)). The eluted object product was fractionated in test tubes, and each fraction was analyzed by HPLC to specify fractions containing only the object product. They were combined and freeze-dried to give 316 mg of a white powder. (0327) The obtained purified sample (316 mg) was dissolved in HO (40 mL), and AG 1x8 AcO resin (2.85 mL, 3.42 mmol equivalents) was added. The solution was stood for 1 hr while occasionally stirring with hand, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, concentrated in an evaporator to reduce the liquid amount to about 5 mL, and the solution was freeze-dried to give 173 mg of a white powder. MALDI-TOF-MS analysis, (M+H) 1935.5 (Calculated 1935.1) HPLC elution time: 7.6 min elution condition (HPLC mode g): column: SHISEIDO CAPCELL PAK C18 MGII(4.6×100 mm) eluent: using Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, A/B: 80/20 - 30/70 linear concentration gradient elution (25 min) flow rate: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0324-0327

35
Cha-Aib-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin [ No CAS ]
[ 27532-96-3 ]
Fmoc-Ser(OtBu)-OH [ No CAS ]
[ 71989-31-6 ]
[ 530-62-1 ]
[ 169555-95-7 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
(carboxymethyl)carbamoyl-[D-Pro₂₄,Pya⁽⁴⁾26,Cha₂₇,36,Aib₂₈,31,Lys₃₀]-PYY(23-36) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
184 mg		Example 27] (0328) (Synthesis method AA): Production of (carboxymethyl)carbamoyl-[D-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys30]-PYY(23-36) (compound No. 287) Compound No. 287: (0329) Synthesis of (Carboxymethyl)carbamoyl-[D-Pro24,Pya(4)26,Cha27,36,Aib28,31,Lys30]-PYY(23-36) (0330) Cha-Aib-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin (0.375 mmol) obtained in Example 26 was weighed and placed in a reaction vessel, washed with DMF, and stirred in DMF for 20 min to swell the resin. Then, the resin was treated with Fmoc-Pya(4)-OH (1165.3 mg, 3 mmol), 0.5 M HOAt/DMF solution (3 mL, 4 mmol), DIPCDI (0.477 mL, 3 mmol) for 75 min to introduce Pya(4) residue. In this case, DIEA (0.5226 mL, 3 mmol) was added to the reaction solution during condensation. The N-terminal Fmoc group was removed by 20% piperidine/DMF treatment. By a similar procedure, Arg(Pbf) was introduced. In the same manner, removal of Fmoc group and condensation were repeated to introduce D-Pro, Ser(But), and the obtained resin was washed with MeOH and dried to give H-Ser(But)-D-Pro-Arg(Pbf)-Pya(4)-Cha-Aib-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin. The obtained resin was washed with DMF and, after swelling, treated with CDI (304.0 mg, 1.88 mmol), DIEA (0.327 mL, 1.88 mmol), DMF (3 mL) for 60 min. The resin was washed, and further treated for 60 min under similar conditions. After washing, the resin was treated with H-Gly-OBut hydrochloride (503 mg, 3 mmol), DIEA (0.523 mL, 3 mmol), DMF (3 mL) for 4 hr, and washed and dried. (0331) The obtained resin (1.69 g) was treated with TFA: thioanisole: m-cresol: H2O: EDT: TIS (80:5:5:5:2.5:2.5) (20 mL) for 4 hr, the reaction solution was added to diethyl ether under ice-cooling while removing the resin with a.filter to give precipitate, and an operation to remove the supernatant after centrifugation was repeated 3 times. The residue was dissolved in aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and concentrated in an evaporator. After confirmation of the purity of the obtained crude peptide solution by HPLC, it was purified in 7 portions by preparative HPLC using YMC Pack R&D-ODS-5-B S-5 120A column (30×250 mm) (Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, flow rate 15 mL/min, A/B: 78/22-68/32 linear concentration gradient elution (60 min)). The eluted object product was fractionated in test tubes, and each fraction was analyzed by HPLC to specify fractions containing only the object product. They were combined and freeze-dried to give 233 mg of a white powder. (0332) The obtained purified sample (233 mg) was dissolved in CHCN/HO (10/20 mL), and AG 1x8 AcO resin (2.60 mL), 3.125 mmol equivalents) was added. The solution was stood for 1 hr while occasionally stirring with hand, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, concentrated in an evaporator to reduce the liquid amount to about 5 mL, and the solution was freeze-dried to give 184 mg of a white powder. MALDI-TOF-MS analysis, (M+H)1867.1 (Calculated 1867.1) HPLC elution time: 7.1 min elution condition (HPLC mode g): column: SHISEIDO CAPCELL PAK C18 MGII(4.6×100 mm) eluent: using Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, A/B: 80/20 - 30/70 linear concentration gradient elution (25 min) flow rate: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0328-0332

36
[ 857478-30-9 ]
Fmoc-D-Hyp [ No CAS ]
H-Cha-Leu(Me)-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide Resin [ No CAS ]
Fmoc-Ser(OtBu)-OH [ No CAS ]
[ 530-62-1 ]
[ 169555-95-7 ]
[ 56-12-2 ]
(3-carboxypropyl)carbamoyl-[D-Hyp₂₄,Iva₂₅,Pya⁽⁴⁾26,Cha₂₇,36,Leu(Me)28,Lys₃₀,Aib₃₁]-PYY(23-36) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
222 mg		[Example 32] (0345) (Synthesis method AF): Production of (3-carboxypropyl)carbamoyl-[D-Hyp24,Iva25,Pya(4)26,Cha27,36,Leu(Me)28, Lys30,Aib31]-PYY(23-36) (compound No. 349) Compound No. 349: (0346) Synthesis of (3-carboxypropyl)carbamoyl-[D-Hyp24,Iva25,Pya(4)26,Cha27,36,Leu(Me)28,Lys30,Aib31]-PYY(23-36) (0347) Using commercially available Sieber Amide resin (391 mg, 0.25 mmol) as a starting material, and ABI433A peptide synthesizer DCC/HOBt 0.25 mmol protocol, amino acids were condensed in the order of Cha, Arg(Pbf), Gln(Trt), Arg(Pbf), Thr(But), Aib, Lys(Boc), Asn(Trt), Leu(Me), Cha to give H-Cha-Leu(Me)-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide Resin (SEQ ID NO:183). In this case, the protocol was partly modified, and capping protocol with acetic anhydride was incorporated after every condensation procedure. In addition, the 30-position Lys(Boc) condensation was performed by double coupling. The obtained resin was swollen with DMF, and treated with Fmoc-Pya(4)-OH (388 mg, 1.0 mmol), HOAt in DMF (0.5 M, 2.0 mL, 1.0 mmol), DIPEA (174 muL, 1.0 mmol), DIPCDI (159 muL, 1.0 mmol) for 3 hr. Fmoc group was removed with 20% piperidine in DMF and the resin was treated with <strong>[857478-30-9]Fmoc-Iva-OH</strong> (339 mg, 1.0 mmol), HOAt in DMF (0.5 M, 2.0 mL, 1.0 mmol), DIPCDI (159 muL, 1.0 mmol) for 2 hr. The resin was washed with DMF, and further treated overnight with <strong>[857478-30-9]Fmoc-Iva-OH</strong> (339 mg, 1.0 mmol), HOAt in DMF (0.5 M, 2.0 mL, 1.0 mmol), DIPCDI (159 muL, 1.0 mmol). The resin was washed and subjected to a capping treatment with decanoic anhydride (368 muL, 1.0 mmol), DIEA (174 muL, 1.0 mmol) in DMF for 20 min. Fmoc group was removed with 20% piperidine in DMF and the resin was treated with Fmoc-D-Hyp-OH (409 mg, 1.0 mmol), HOAt in DMF (0.5 M, 2.0 mL, 1.0 mmol), DIPCDI (159 muL, 1.0 mmol) for 6 hr. The resin was washed, and the resin was subjected to a capping treatment with decanoic anhydride (368 muL, 1.0 mmol), DIEA (174 muL, 1.0 mmol) in DMF for 30 min. Fmoc group was removed with 20% piperidine in DMF and the resin was treated with Fmoc-Ser(But)-OH (383 mg, 1.0 mmol), HOAt in DMF (0.5 M, 2.0 mL, 1.0 mmol), DIPCDI (159 muL, 1.0 mmol) for 2 hr. The resin was washed, and the resin was subjected to a capping treatment with decanoic anhydride (368 muL, 1.0 mmol), DIEA (174 muL, 1.0 mmol) in DMF for 30 min. Fmoc group was removed with 20% piperidine in DMF and the resin was washed successively with DMF, MeOH and dried under reduced pressure. The total amount of the obtained H-Ser(But)-D-Hyp(But)-Iva-Pya(4)-Cha-Leu(Me)-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin was swollen again with DMF, and treated with CDI (203 mg, 1.25 mmol), DIEA (218 muL, 1.25 mmol) in DMF for 2 hr. The resin was washed with DMF, and treated with 4-aminobutyric acid (206 mg, 2.0 mmol), DIEA (523 muL, 3.0 mmol) in DMF for 24 hr. The resin was washed successively with DMF, MeOH, dried under reduced pressure and the obtained resin (1.13 g) was suspended in TFA: thioanisole: m-cresol: H2O: EDT: TIS (80:5:5:5:2.5:2.5) (10 mL) and the suspension was stirred at room temperature for 7 hr. The reaction solution was added to stirring diethyl ether under ice-cooling while removing the resin by a filter to obtain precipitation, and an operation to remove the supernatant after centrifugation was repeated 3 times. The residue was extracted with 50% aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and purified in 4 portions by HPLC. The HPLC conditions were YMC Pack R&D-ODS-5-B S-5 120A column (30x250 mm), Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, flow rate 15 mL/min, A/B: 74.5/25.5-64.5/35.5 or 74/26-64/36 linear concentration gradient elution (60 min). Each fraction was analyzed by HPLC to specify fractions containing only the object product. The fractions with low purity obtained by the first purification were concentrated, and subjected to HPLC purification again under the same conditions. All the fractions containing only the object product were combined and freeze-dried to give 345 mg of a white powder. (0348) The obtained purified sample (345 mg) was dissolved in CHCN/HO (10/20 mL), and AG 1x8 AcO resin (3.03 mL, 3.64 mmol equivalents) was added. The solution was stood for 1 hr while occasionally stirring with hand, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, concentrated in an evaporator to reduce the liquid amount to about 5 mL, and the solution was freeze-dried to give 222 mg of a white powder. MALDI-TOF-MS analysis, (M+H)1896.3 (Calculated 1896.1) HPLC elution time: 10.4 min elution condition (HPLC mode g): column: SHISEIDO CAPCELL PAK C18 MGII(4.6×100 mm) eluent: using Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, A/B: 80/.20 - 30/70 linear concentration gradient elution (25 min) flow rate: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0345-0348

37
[ 857478-30-9 ]
[ 14464-29-0 ]
H-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin [ No CAS ]
Fmoc-D-Hyp [ No CAS ]
Fmoc-Ser(OtBu)-OH [ No CAS ]
[ 135673-97-1 ]
[ 169555-95-7 ]
Ac-Ser-D-Hyp-Iva-Pya⁽⁴⁾-Cha-Iva-Asn-Lys-Aib-Thr-Arg-Gln-Arg-Cha-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
186.1 mg		Example 29] (0337) (Synthesis method AC): Production of Ac-[D-Hyp24,Iva25,28,Pya(4)26,Cha27,36,Lys30,Aib31]-PYY(23-36) (compound No. 298) Compound No. 298: (0338) Synthesis of Ac-[D-Hyp24,Iva25,28,Pya(4)26,Cha27,36,Lys30,Aib31]-PYY (23-36) (0339) H-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin (SEQ ID NO:177) (952.8 mg, 0.25 mmol) obtained in Example 20 was weighed and placed in a reaction vessel, washed with DMF, and stirred in DMF for 20 min to swell the resin. Then, the resin was treated with <strong>[857478-30-9]Fmoc-Iva-OH</strong> (339.4 mg, 1 mmol), 0.5 M HOAt/DMF solution (2 mL, 1 mmol), DIPCDI (159 muL, mmol) for 120 min. The N-terminal Fmoc group was removed by 20percent piperidine/DMF treatment. By a similar procedure, Cha was introduced. In the same manner, removal of Fmoc group and condensation were repeated to introduce Pya(4), Iva, D-Hyp, Ser(But). After removal of Fmoc, the obtained resin was treated with AcOSu (157.1 mg, 1 mmol), DIEA (174.2 muL, 1 mmol) in DMF for 60 min, and washed with MeOH and dried to give Ac-Ser(But)-D-Hyp-Iva-Pya(4)-Cha-Iva-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin (1.1162 g). The obtained resin (1.1162 g) was treated with TFA: thioanisole: m-cresol: H2O: EDT: TIS (80:5:5:5:2.5:2.5) (6 mL) for 120 min, an operation to add diethyl ether to the reaction solution, precipitate a white powder by centrifugation, and remove diethyl ether by decantation was repeated twice. The residue was dissolved in aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and concentrated in an evaporator. After confirmation of the purity of the obtained crude peptide solution by HPLC, the peptide was purified by preparative HPLC in 6 portions using Daisopak-SP100-5-ODS-P 2×25 cm, and Solution A: 0.1percent TFA-water, Solution B: 0.1percent TFA-containing acetonitrile, flow rate 8 mL/min, A/B: 75/25-65/35 linear concentration gradient elution (60 min) was performed. The eluted object product was fractionated in test tubes, and each fraction was analyzed by HPLC to specify fractions containing only the object product. They were combined and freeze-dried to give 250.2 mg of a white powder. (0340) The obtained purified sample (250.2 mg, 140.47 mumol) was dissolved in water (20 mL), and AG 1x8 AcO resin (2.34 mL, 2.81 mmol equivalents) was added. The solution was stood for 1 hr while occasionally stirring with hand, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, concentrated in an evaporator to reduce the liquid amount to about 5 mL, and the solution was freeze-dried by cooling in a dry ice bath to give 186.1 mg of a white powder. MALDI-TOF-MS analysis, (M+H)1780.6 (Calculated 1781.1) HPLC elution time: 9.2 min elution condition (HPLC mode d): column: Merck Chromolith Performance RP-18e(4.6×100 mm I.D.) eluent: using Solution A: 0.1percent TFA-water, Solution B: 0.1percent TFA-containing acetonitrile, A/B: 80/20 - 30/70 linear concentration gradient elution (25 min) flow rate: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0337-0340

38
[ 857478-30-9 ]
H-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin [ No CAS ]
Fmoc-D-Hyp [ No CAS ]
Fmoc-Ser(OtBu)-OH [ No CAS ]
(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4,4-dimethylpentanoic acid [ No CAS ]
[ 135673-97-1 ]
[ 169555-95-7 ]
[ 191103-80-7 ]
4-Imidazolecarbonyl-Ser-D-Hyp-Iva-Pya⁽⁴⁾-Cha-Leu(Me)-Asn-Lys-Aib-Thr-Arg-Gln-Arg-Cha-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
303.2 mg		Example 31] (Synthesis method AE): Production of 4-Imidazolecarbonyl-[D-Hyp24,Iva25,Pya(4)26,Cha27,36,Leu(Me)28,Lys30,Aib31]-PYY(23-36) (compound No. 336) Compound No. 336: (0342) Synthesis of 4-imidazolecarbonyl-[D-Hyp24,Iva25,Pya(4)26,Cha27,36,Leu(Me)28, Lys30,Aib31]-PYY(23-36) (0343) H-Asn (Trt) -Lys (Boc) -Aib-Thr(But) -Arg (Pbf) -Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin (1.795 g, 0.5 mmol) obtained in Example 20 was weighed and placed in a reaction vessel, washed with DMF, and stirred in DMF for 20 min to swell the resin. Then, the resin was treated with Fmoc-Leu(Me)-OH (734.8 mg, 2 mmol), 0.5 M HOAt/DMF solution (4 mL, 2 mmol), DIPCDI (0.318 mL, 2 mmol) for 120 min to introduce Leu(Me) residue. The N-terminal Fmoc group was removed by 20% piperidine/DMF treatment. By a similar procedure, Cha was introduced. In the same manner, removal of Fmoc group and condensation were repeated to introduce Pya(4), Iva. The obtained resin was washed with MeOH and dried to give H-Iva-Pya(4)-Cha-Leu(Me)-Asn(Trt)-Lys(Boc)-Aib-Thr(But)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieber Amide resin (SEQ ID NO:181) (2.1612 g). In this case, for introduction of Pya(4) residue, DIEA (348.4 muL, 2 mmol) was added to the reaction solution during condensation. The obtained resin (1.0806 g, 0.25 mmol) was washed with DMF and, after swelling, treated with Fmoc-D-Hyp-OH (353.4 mg, 1 mmol), 0.5 M HOAt/DMF solution (2 mL, 1 mmol), DIPCDI (159 muL, 1 mmol) for 15 hr to introduce D-Hyp. Fmoc group was removed, and Ser(But) was similarly introduced. After removal of Fmoc from the obtained Fmoc-Ser(But)-D-Hyp-Iva-Pya(4)-Cha-Leu(Me)-Asn(Trt)-Lys(Boc)-Aib-Thr (But) -Arg (Pbf) -Gln (Trt) -Arg (Pbf) -Cha-Sieber amide resin, the resin was treated with 1-trityl-1H-imidazole-4-carboxylic acid (354.4 mg, 1 mmol), DIPCDI (159 muL, 1 mmol) in DMSO (1 mL), 0.5 M HOAt/DMF solution (2 mL, 1 mmol) for 120 min, and the resin was washed and dried. The obtained resin (1.2067 g) was treated with TFA: thioanisole: m-cresol: H2O: EDT: TIS (80:5:5:5:2.5:2.5) (6 mL) for 120 min, an operation to add diethyl ether to the reaction solution, precipitate a white powder by centrifugation, and remove diethyl ether by decantation was repeated twice. The residue was dissolved in aqueous acetic acid solution, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, and concentrated in an evaporator. After confirmation of the purity of the obtained crude peptide solution by HPLC, the peptide was purified by preparative HPLC in 6 portions using Daisopak-SP100-5-ODS-P 2×25 cm, and Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, flow rate 8 mL/min, A/B: 74/26-64/36 linear concentration gradient elution (60 min) was performed. The eluted object product was fractionated in test tubes, and each fraction was analyzed by HPLC to specify fractions containing only the object product. They were combined and freeze-dried to give 365.5 mg of a white powder. (0344) The obtained purified sample (365.5 mg, 196.38 mumol) was dissolved in water (30 mL), and AG 1x8 AcO resin (4.09 mL, 4.91 mmol equivalents) was added. The solution was stood for 1 hr while occasionally stirring with hand, passed through a disc filter with a pore diameter 0.45 mum to remove fine granules, concentrated in an evaporator to reduce the liquid amount to about 5 mL, and the solution was freeze-dried by cooling in a dry ice bath to give 303.2 mg of a white powder. MALDI-TOF-MS analysis, (M+H)1860.9 (Calculated 1861.1) HPLC elution time: 9.9 min elution condition (HPLC mode d): column: Merck Chromolith Performance RP-18e(4.6×100 mm I.D.) eluent: using Solution A: 0.1% TFA-water, Solution B: 0.1% TFA-containing acetonitrile, A/B: 80/20 - 30/70 linear concentration gradient elution (25 min) flow rate: 1.0 mL/min

Reference： [1]Patent: EP2450374,2015,B1 .Location in patent: Paragraph 0342-0344

39
[ 16937-99-8 ]
3-acetamido-N-(2-aminoethyl)propanamide hydrogen chloride [ No CAS ]
[ 71989-38-3 ]
[ 132388-59-1 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
[ 169555-95-7 ]
Fmoc-D-4-Hpg(PG)-OH [ No CAS ]
C₅₁H₆₅N₁₁O₁₂ [ No CAS ]

Reference： [1]MedChemComm,2016,vol. 7,p. 132 - 140

40
[ 143-07-7 ]
[ 169555-95-7 ]
C₂₀H₃₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 22 Preparation of C12-[4-Pal(N-CH3)]-C12 4-(3-(dodecylamino)-3-oxo-2-dodecanamidopropyl)-1-methylpyridinium chloride (0623) Fmoc-4-Pal-resin. To 6.5 g of 2-chlorotrityl chloride resin with 1.3 mmol/g substitution (Novabiochem, 01-64-0114) in 70 ml of dry DCM in 200 ml reaction vessel for solid phase synthesis, 3.5 g (9.01 mmol, 1.5 eq) of Fmoc-4-Pal-OH (Fmoc-4-Pyridinylalanine, Mw=388.42, Advanced ChemTech, FX4140) and 3.132 ml (18 mmol, 2.2 eq) of DIPEA (Aldrich, Mw=129.2, d=0.74) were added. (0624) 4-Pal-resin. After 2 hrs the resin was washed 3× with DCM/MeOH/DIPEA (17:2:1), 3×DCM, 2×DMF, 3×DCM and Fmoc group was deprotected 2* with 70 ml of 20% piperidine/DMF for 15 min. (0625) C12-4-Pal-resin. After Fmoc deprotection the resin was washed with 3×DCM, 2×MeOH and 3×DCM and for the coupling reaction 2.549 g (12.675 mmol, 1.5 eq) of lauric acid (Sigma, Mw=200.32), 5.3 g (12.675 mmol) of HCTU (Mw=417.7) and 2.2 ml (12.675 mmol) of DIPEA (Mw=129.2, d=0.74) in 70 ml of DMF were added. (0626) After 1 hr of reaction the resin was washed with 3×DCM, 2×MeOH and 3×DCM and progress of reaction was checked by Kaiser test which was negative (no free amine groups present). (0627) C12-4-Pal-OH (Mw=346.7) was cleaved from the resin by 1% TFA/DCM (5×30 ml for 2 min was filtered to flask with 2 ml 10% pyridine/MeOH) and solvent was evaporated. (0628) C12-4-Pal-C12 (Mw=515.7). Second coupling was carried out in solution. To the oily residue from the previous reaction 2.3 g (12 mmol) of EDCHCl (Mw=191.7), 1.86 g (12 mmol) of HOBtH2O (Mw=153.1) and 10.44 ml (60 mmol, 5 eq) of DIPEA (Mw=129.2, d=0.74) in 70 ml of DCM were added. Preactivation step was carried out for 20 min and then 2.22 g (12 mmol) of C12-amine (Sigma, Mw=185.36) was added. After overnight reaction the organic layer was washed in reparatory funnel with 3×0.5 M HCl, 3×10% NaCO3 and 3×NaCl. DCM was dried with anhydrous MgSO4 and evaporated. The product was purified on TELEDYNE Isco CombiFlash Rf instrument, 40 g normal phase silica gel column, 100% DCM for 5 CV (column volume) and 0-5% MeOH for 10 CV, detection 254 nm, flow 40 ml/min. (0629) C12-4-Pal(Me)-C12 (Mw=530.8). Methylation was carried out in solution. To 4 g (7.75 mM) of C12-4-Pal-C12 (Mw=415.7) dissolved in 50 ml of THF, 1.1 ml (11.625 mmol) of dimethyl sulfate (Sigma, Mw=126.13, d=1.325) was added. After overnight reaction 0.5 ml of dimethyl sulfate was added and after 1 hr the solvent was evaporated and the product was precipitated with 0.5 M HCl.

Reference： [1]Patent: US9339461,2016,B2 .Location in patent: Page/Page column 87-88

41
[ 112-80-1 ]
[ 169555-95-7 ]
C₂₆H₄₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 23 Preparation of C18oleic-[4-Pal]-C16 N-(1-oxo-3-(pyridin-4-yl)-1-(hexadecylamino)propan-2-yl)octadec-9-enamide (0630) Fmoc-4-Pal-resin. To 5 g of 2-chlorotrityl chloride resin with 1.3 mmol/g substitution (Novabiochem, 01-64-0114) in 50 ml of dry DCM in 50 ml reaction vessel for solid phase synthesis 3.787 g (9.75 mmol, 1.5 eq) of Fmoc-4-Pal-OH (Mw=388.42, Advanced ChemTech) and 1.7 ml (9.75 mmol, 1.5 eq) of DIPEA (Aldrich, Mw=129.2, d=0.74) were added. (0631) 4-Pal-resin. After 2 hrs the resin was washed 3× with DCM/MeOH/DIPEA (17:2:1), 3×DCM, 2×DMF, 3×DCM and Fmoc group was deprotected with 40 ml of 20% piperidine/DMF 2 times for 15 min. (0632) C18oleic-4-Pal-resin. After Fmoc deprotection the resin was washed with 3×DCM, 2×MeOH and 3×DCM and for the coupling reaction 3.7 g (13 mmol) of oleic acid (Sigma, Mw=282.47, d=0.891), 5.37 g (13 mmol) of HCTU (Mw=413.7) and 2.62 ml (13 mmol) of DIPEA (Mw=129.2, d=0.74) in 50 ml of DMF were added. (0633) After 2 hr of reaction the resin was washed with 3×DCM, 2×MeOH and 3×DCM and progress of reaction was checked by Kaiser test which was negative (no free amine groups present). (0634) C18oleic-4-Pal-OH (Mw=430.62) was cleaved from the resin by 1% TFA/DCM (5×50 ml for 2 min was filtered to flask with 2 ml 10% pyridine/MeOH) and solvent was evaporated. (0635) C18oleic-4-Pal-C16 (Mw=654.06). Second coupling was carried out in solution. To the oily residue from the previous reaction, 2.354 g (9.75 mmol) of C16-amine (Sigma, Mw=241.46), 4.033 g (9.75 mmol) of HCTU (Mw=413.7) and 1.69 ml (9.75 mmol) of DIPEA (Mw=129.2, d=0.74) in 50 ml of DMF were added. After 4 hr 100 ml of AcOEt was added and organic layer was washed in reparatory funnel with 3×0.5 M HCl, 3×10% NaCO3 and 3×NaCl. AcOEt layer was dried with anhydrous MgSO4 and evaporated. Crude product was purified on TELEDYNE Isco CombiFlash Rf instrument using 48 g normal phase silica gel column, 100% DCM for 3 CV (column volume) and 0-20% MeOH for 10 CV, detection 214 nm, flow 45 ml/min. DCM/MeOH was evaporated and residue was precipitated by 0.1M HCl. Yield: 0.75 g.

Reference： [1]Patent: US9339461,2016,B2 .Location in patent: Page/Page column 88-89

42
[ 882-06-4 ]
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 169555-95-7 ]
NAA-Gly-Ala(4-pyridyl)-Gly-Leu-NH2 [ No CAS ]

Reference： [1]Journal of Peptide Science,2016,p. 600 - 606

43
Fmoc-Thr(tBu)-Resin [ No CAS ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 35661-40-6 ]
[ 71989-33-8 ]
[ 71989-14-5 ]
[ 71989-38-3 ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 71989-28-1 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 109425-51-6 ]
[ 94744-50-0 ]
[ 169555-95-7 ]
[ 143824-78-6 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
Gcg[4-Pal₁₃, Aib₁₆] [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 8061 - 8067

44
Fmoc-Thr(tBu)-Resin [ No CAS ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 35661-40-6 ]
[ 71989-33-8 ]
[ 71989-14-5 ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 71989-28-1 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 109425-51-6 ]
[ 94744-50-0 ]
[ 169555-95-7 ]
[ 143824-78-6 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
Gcg[4-Pal₆,10,13, Aib₁₆] [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 8061 - 8067

45
Fmoc-Thr(tBu)-Resin [ No CAS ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 35661-40-6 ]
[ 71989-33-8 ]
[ 71989-14-5 ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 71989-28-1 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 109425-51-6 ]
[ 94744-50-0 ]
[ 169555-95-7 ]
[ 143824-78-6 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
Gcg[4-Pal₁₀,13, Aib₁₆] [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 8061 - 8067

46
[ 857478-30-9 ]
C₁₁₇H₁₅₇N₁₈O₁₉PolS₂ [ No CAS ]
[ 71989-33-8 ]
(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4,4-dimethylpentanoic acid [ No CAS ]
[ 135673-97-1 ]
[ 169555-95-7 ]
[ 191103-80-7 ]
[ 139262-20-7 ]
4-Imidazolecarbonyl-Ser-D-Hyp-Iva-Pya⁽⁴⁾-Cha-Leu(Me)-Asn-Lys-Aib-Thr-Arg-Gln-Arg-Cha-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		All peptides were synthesized in the same manner following thesynthesis procedure for 4-imidazolecarbonyl-[D-Hyp24,Iva25,Pya(4)26,Cha27,36,cMeLeu28,Lys30,Aib31]PYY(23-36) (31). Using a commerciallyavailable Sieber amide resin (391 mg, 0.25 mmol) as astarting material and the ABI 433A peptide synthesizer (DCC/HOBt0.25-mmol protocol), amino acids were successively condensed togive H-Asn(Trt)-Lys(Boc)-Aib-Thr(tBu)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-NH-Sieber Amide Resin (903 mg, 0.289 mmol/g). A 34.6-mg(0.01 mmol) aliquot of the obtained resin was weighed, washedwith DMF, and after swelling, treated with Fmoc-cMeLeu-OH(18.4 mg, 0.05 mmol), DIPCDI (8.0 lL, 0.05 mmol), and 0.5 MHOAt/DMF (0.1 mL, 0.05 mmol) in DMF for 90 min to introducecMeLeu residue on position 28. The resin was treated with 20%piperidine/DMF to remove N-terminal Fmoc group, then Cha wasintroduced on position 27 in the same manner. Pya(4), Iva,D-Hyp, Ser(tBu) and N-terminal 1-trityl-1H-imidazole-4-carboxylicacid were introduced by repeating the same steps. The resin waswashed with DMF, methanol, and dried to give 1-trityl-1Himidazole-4-carbonyl-Ser(tBu)-D-Hyp-Iva-Pya(4)-Cha-cMeLeu-Asn(Trt)-Lys(Boc)-Aib-Thr(tBu)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieberamide resin (43.0 mg, 0.01 mmol). Trifluoroacetic acid (TFA):thioanisole:m-cresol:H2O:1,2-ethanedithiol:triisopropylsilane (80:5:5:5:2.5:2.5) (0.4 mL) was added to the entire amount of the obtainedresin, then the mixture was stirred at ambient temperature for90 min, and diethyl ether was added to the reaction solution to allowprecipitation of a white powder. Diethyl ether was removed bydecantation after centrifugation of the suspension, and the procedurewas repeated to remove acid and the scavenger. The residuewas extracted with an aqueous acetic acid solution and purified bypreparative HPLC using a Daisopak-SP100-5-ODS-P column(250 20mmi.d.) to give 5.1 mgof a white powder. Mass spectrum:MALDI-TOF (a-cyano-4-hydroxycinnaminic acid, monoisotopic) [M+H]+ 1861.25 (calcd. 1861.09). Elution time on RP-HPLC: 6.43 min.Elution conditions: a Phenomenex Kinetex XB-C18 column(1.7 mm, 100 2.1 mm i.d.), linear density-gradient elution witheluents A/B = 95/5-45/55 (10 min) using 0.1% TFA in water as eluentA and 0.1% TFA-containing acetonitrile as eluent B; flow rate:0.5 mL/min.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5718 - 5725

47
[ 857478-30-9 ]
[ 1231709-22-0 ]
C₁₁₇H₁₅₇N₁₈O₁₉PolS₂ [ No CAS ]
[ 71989-33-8 ]
[ 135673-97-1 ]
[ 169555-95-7 ]
[ 191103-80-7 ]
[ 139262-20-7 ]
4-Imidazolecarbonyl-Ser-D-Hyp-Iva-Pya⁽⁴⁾-Cha-Iva-Asn-Lys-Aib-Thr-Arg-Gln-Arg-,Cha-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: All peptides were synthesized in the same manner following thesynthesis procedure for 4-imidazolecarbonyl-[D-Hyp24,Iva25,Pya(4)26,Cha27,36,cMeLeu28,Lys30,Aib31]PYY(23-36) (31). Using a commerciallyavailable Sieber amide resin (391 mg, 0.25 mmol) as astarting material and the ABI 433A peptide synthesizer (DCC/HOBt0.25-mmol protocol), amino acids were successively condensed togive H-Asn(Trt)-Lys(Boc)-Aib-Thr(tBu)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-NH-Sieber Amide Resin (903 mg, 0.289 mmol/g). A 34.6-mg(0.01 mmol) aliquot of the obtained resin was weighed, washedwith DMF, and after swelling, treated with Fmoc-cMeLeu-OH(18.4 mg, 0.05 mmol), DIPCDI (8.0 lL, 0.05 mmol), and 0.5 MHOAt/DMF (0.1 mL, 0.05 mmol) in DMF for 90 min to introducecMeLeu residue on position 28. The resin was treated with 20%piperidine/DMF to remove N-terminal Fmoc group, then Cha wasintroduced on position 27 in the same manner. Pya(4), Iva,D-Hyp, Ser(tBu) and N-terminal 1-trityl-1H-imidazole-4-carboxylicacid were introduced by repeating the same steps. The resin waswashed with DMF, methanol, and dried to give 1-trityl-1Himidazole-4-carbonyl-Ser(tBu)-D-Hyp-Iva-Pya(4)-Cha-cMeLeu-Asn(Trt)-Lys(Boc)-Aib-Thr(tBu)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieberamide resin (43.0 mg, 0.01 mmol). Trifluoroacetic acid (TFA):thioanisole:m-cresol:H2O:1,2-ethanedithiol:triisopropylsilane (80:5:5:5:2.5:2.5) (0.4 mL) was added to the entire amount of the obtainedresin, then the mixture was stirred at ambient temperature for90 min, and diethyl ether was added to the reaction solution to allowprecipitation of a white powder. Diethyl ether was removed bydecantation after centrifugation of the suspension, and the procedurewas repeated to remove acid and the scavenger. The residuewas extracted with an aqueous acetic acid solution and purified bypreparative HPLC using a Daisopak-SP100-5-ODS-P column(250 20mmi.d.) to give 5.1 mgof a white powder. Mass spectrum:MALDI-TOF (a-cyano-4-hydroxycinnaminic acid, monoisotopic) [M+H]+ 1861.25 (calcd. 1861.09). Elution time on RP-HPLC: 6.43 min.Elution conditions: a Phenomenex Kinetex XB-C18 column(1.7 mm, 100 2.1 mm i.d.), linear density-gradient elution witheluents A/B = 95/5-45/55 (10 min) using 0.1% TFA in water as eluentA and 0.1% TFA-containing acetonitrile as eluent B; flow rate:0.5 mL/min.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5718 - 5725

48
[ 857478-30-9 ]
C₁₁₇H₁₅₇N₁₈O₁₉PolS₂ [ No CAS ]
[ 71989-33-8 ]
[ 94744-50-0 ]
[ 135673-97-1 ]
[ 169555-95-7 ]
[ 191103-80-7 ]
[ 139262-20-7 ]
4-Imidazolecarbonyl-Ser-D-Hyp-Iva-Pya⁽⁴⁾-Cha-Aib-Asn-Lys-Aib-Thr-Arg-Gln-Arg-Cha-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: All peptides were synthesized in the same manner following thesynthesis procedure for 4-imidazolecarbonyl-[D-Hyp24,Iva25,Pya(4)26,Cha27,36,cMeLeu28,Lys30,Aib31]PYY(23-36) (31). Using a commerciallyavailable Sieber amide resin (391 mg, 0.25 mmol) as astarting material and the ABI 433A peptide synthesizer (DCC/HOBt0.25-mmol protocol), amino acids were successively condensed togive H-Asn(Trt)-Lys(Boc)-Aib-Thr(tBu)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-NH-Sieber Amide Resin (903 mg, 0.289 mmol/g). A 34.6-mg(0.01 mmol) aliquot of the obtained resin was weighed, washedwith DMF, and after swelling, treated with Fmoc-cMeLeu-OH(18.4 mg, 0.05 mmol), DIPCDI (8.0 lL, 0.05 mmol), and 0.5 MHOAt/DMF (0.1 mL, 0.05 mmol) in DMF for 90 min to introducecMeLeu residue on position 28. The resin was treated with 20%piperidine/DMF to remove N-terminal Fmoc group, then Cha wasintroduced on position 27 in the same manner. Pya(4), Iva,D-Hyp, Ser(tBu) and N-terminal 1-trityl-1H-imidazole-4-carboxylicacid were introduced by repeating the same steps. The resin waswashed with DMF, methanol, and dried to give 1-trityl-1Himidazole-4-carbonyl-Ser(tBu)-D-Hyp-Iva-Pya(4)-Cha-cMeLeu-Asn(Trt)-Lys(Boc)-Aib-Thr(tBu)-Arg(Pbf)-Gln(Trt)-Arg(Pbf)-Cha-Sieberamide resin (43.0 mg, 0.01 mmol). Trifluoroacetic acid (TFA):thioanisole:m-cresol:H2O:1,2-ethanedithiol:triisopropylsilane (80:5:5:5:2.5:2.5) (0.4 mL) was added to the entire amount of the obtainedresin, then the mixture was stirred at ambient temperature for90 min, and diethyl ether was added to the reaction solution to allowprecipitation of a white powder. Diethyl ether was removed bydecantation after centrifugation of the suspension, and the procedurewas repeated to remove acid and the scavenger. The residuewas extracted with an aqueous acetic acid solution and purified bypreparative HPLC using a Daisopak-SP100-5-ODS-P column(250 20mmi.d.) to give 5.1 mgof a white powder. Mass spectrum:MALDI-TOF (a-cyano-4-hydroxycinnaminic acid, monoisotopic) [M+H]+ 1861.25 (calcd. 1861.09). Elution time on RP-HPLC: 6.43 min.Elution conditions: a Phenomenex Kinetex XB-C18 column(1.7 mm, 100 2.1 mm i.d.), linear density-gradient elution witheluents A/B = 95/5-45/55 (10 min) using 0.1% TFA in water as eluentA and 0.1% TFA-containing acetonitrile as eluent B; flow rate:0.5 mL/min.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5718 - 5725

49
C₇₆H₇₉ClN₇O₁₀Pol [ No CAS ]
[ 169555-95-7 ]
C₈₄H₈₇ClN₉O₁₁Pol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 9653 - 9663

50
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 64-19-7 ]
[ 169555-95-7 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
[ 378247-75-7 ]
Ac-Ala-Arg-Leu-P₁-(7-amino-4-carbamoylmethylcoumarin), P₁ = L-4-Pal [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 5222 - 5234

51
[ 3235-69-6 ]
[ 159610-93-2 ]
C₂₆H₁₉N₂O₅Pol [ No CAS ]
[ 132684-59-4 ]
[ 169555-95-7 ]
Mor-Hfe-Ser(Me)-4-Pal-ACC [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2018,vol. 140,p. 11424 - 11437

52
[ 3235-69-6 ]
[ 35661-60-0 ]
C₂₆H₁₉N₂O₅Pol [ No CAS ]
[ 132684-59-4 ]
[ 169555-95-7 ]
Mor-Hfe-4-Pal-Leu-ACC [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2018,vol. 140,p. 11424 - 11437

53
[ 3235-69-6 ]
[ 159610-93-2 ]
[ 35661-60-0 ]
C₂₆H₁₉N₂O₅Pol [ No CAS ]
[ 169555-95-7 ]
Mor-4-Pal-Ser(Me)-Leu-ACC [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2018,vol. 140,p. 11424 - 11437

54
[ 108-24-7 ]
[ 169555-95-7 ]
[ 143824-78-6 ]
Fmoc-4-phenyl-D-phenylalanine [ No CAS ]
Fmoc-Arg(*)-OH [ No CAS ]
Ac-4Pal-DBip-Arg-Trp-NH2 [ No CAS ]

Reference： [1]ACS Chemical Neuroscience,2018

55
[ 108-24-7 ]
[ 169555-95-7 ]
[ 143824-78-6 ]
(R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4-iodophenyl)propanoic acid [ No CAS ]
Fmoc-Arg(*)-OH [ No CAS ]
Ac-4Pal-(pI)DPhe-Arg-Trp-NH2 [ No CAS ]

Reference： [1]ACS Chemical Neuroscience,2018

56
[ 35661-60-0 ]
[ 39608-52-1 ]
C₁₉H₁₉NO₅ [ No CAS ]
[ 169555-95-7 ]
benzyl ((2S)-1-((4-(((S)-1-amino-1-oxo-3-(pyridin-4-yl)propan-2-yl)amino)-3,4-dioxobutan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Step 1 Automated microwave assisted peptide synthesis on Biotage Initiator+ AlstraTM: Synthesizer was set up with the following reagents: DMF, NMP, 20% piperidine in DMF, 1.5 M DIEA in NMP, 0.5 M HATU in DMF, and desired Fmoc-amino acids/Fmoc-amino acid derivatives/ end capping reagents (0.5 M in 1:1 DMF:NMP). The vial containing the Rink amide MBHE resin (with Nle) (0.2 g, 0.1 mmol) was placed in the synthesizer. The instrument was programmed with the following sequence for Fmoc piperidine deprotection and subsequent HATU amino acid coupling. The resin was initially swelled in 4.5 mE DMF for 20 mm. at 70 C. followed by draining of solvent. Deprotection sequence: a) 3.0 mE 20% Piperidine in DMF for 3 mm. at 70 C. b) Reagents were drained. c) 3.0 mE 20% piperidine in DMF for 3 mm. at 70 C. d) Reagents were drained and resin washed with 4.5 mE DMF. Coupling sequence: a) Reaction vial was filled with 5 equivalents Fmoc -amino acid (or reagent), 0.98 equiv. RATU, 1.5 mE DMF and 2 equiv. DIEA. Mixture heated at 75 C. for 5 mi b) Reagents were drained and resin washed with 4.5 mE DMF. The deprotection and coupling sequences were repeated for each amino acid or derivative until peptide was the desired length. Step 2 Oxidation of alcohol on resin: Afier synthesis was complete on the Biotage, the resin was rinsed with DMF followed by DCM and finally DMSO. The resin was mixed with 3 mE DMSO and 5 equiv. 2-iodoxybenzoic acid (IEX) and stirred at rt at least 8 hours. Solvents/reagent were drained off and resin was rinsed with 2-3 mE DMSO followed by 5 mE DCM. Step 3 Cleavage of peptide from resin: Cleavage cocktail of 9:0.5:0.5 TFA:TIPS:R20 (3 mE) was added to the resin and stirred at it for 1.5 hours. Solvents/reagent were drained off and resin was rinsed with 5 mE DCM. Step 4 Purification of final product: After confirming desired product was synthesized by analytical EC/MS, the general purification was using Water system prep-EC/ MS using X-Select Peptide CSR.C18 080 Prep Column, 130 Angstrom, 5 tm, 19 mmxl 50 mm, with elution solvents A=Water with 0.5% Formic acid and E=Acetonitrile with 0.5% Formic acid.

Reference： [1]Patent: US2019/85024,2019,A1 .Location in patent: Paragraph 0168; 0169; 0170; 0171; 0172; 0173; 0261; 0262

57
[ 169555-95-7 ]
CKRK-(L-3-(2-cyano-4-pyridyl)alanine)-NH2 [ No CAS ]