Name: Fmoc-Thr-OH
Brand: Ambeed
SKU: A268866

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Fmoc-Thr-OH is a protected threonine derivative with the amino group protected by 9-fluorenylmethoxycarbonyl (Fmoc), suitable for peptide synthesis.

4.5 *For Research Use Only !

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Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

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Quality Control of Fmoc-Thr-OH Purity: 95% SDS Specification

COA

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NMR

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CNMR

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Product Details of Fmoc-Thr-OH

CAS No. :	73731-37-0
Formula :	C₁₉H₁₉NO₅
M.W :	341.36
SMILES Code :	C[C@@H](O)[C@@H](C(O)=O)NC(OCC1C2=CC=CC=C2C3=CC=CC=C13)=O
MDL No. :	MFCD00077072
InChI Key :	OYULCCKKLJPNPU-DIFFPNOSSA-N
Pubchem ID :	6992530

Safety of Fmoc-Thr-OH

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of Fmoc-Thr-OH

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 73731-37-0 ]

[ 73731-37-0 ] Synthesis Path-Downstream 1~35

1
[ 112883-29-1 ]
[ 96402-49-2 ]
[ 73731-37-0 ]
[ 35737-15-6 ]
N-Fmoc-L-Pro-2-chlorotrityl polystyrene resin [ No CAS ]
N-Fmoc-L-Phe [ No CAS ]
cyclo(1-Nal-D-Trp-Tyr-Thr-Phe-Pro) [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 551 - 559.

2
[ 29022-11-5 ]
[ 35661-40-6 ]
[ 108-24-7 ]
[ 73731-37-0 ]
[ 198561-07-8 ]
Ac-Thr-Asp-Phe-Gly-OH [ No CAS ]

References: [1]Organic Letters,2007,vol. 9,p. 2469 - 2472.

3
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 71989-20-3 ]
[ 91000-69-0 ]
[ 96402-49-2 ]
[ 94744-50-0 ]
Y-(α-aminoisobutyroyl)-EGTFTSDYSIYLDKKAQRAFVNWLLA-(α-aminoisobutyroyl)-KYG-(β-(1-naphthyl)-alaninoyl)-LDF-NH2 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Solid phase peptide synthesis was performed on a CEM Liberty Peptide Synthesizer using standard Fmoc chemistry. TentaGel S Ram resin (1 g; 0.25 mmol/g) was swelled in NMP (10 ml) prior to use and transferred between tube and reaction vessel using DCM and NMP. Coupling (0148) An Fmoc-amino acid in NMP/DMF/DCM (1:1:1; 0.2 M; 5 ml) was added to the resin in a CEM Discover microwave unit together with HATU/DMF or COMU/DMF (0.5 M; 2 ml) and DIPEA/NMP (2.0 M; 1 ml). The coupling mixture was heated to 75° C. for 5 min while nitrogen was bubbled through the mixture. The resin was then washed with NMP (4×10 ml). Deprotection (0149) Piperidine/DMF (20percent; 10 ml) was added to the resin for initial deprotection and the mixture was heated by microwaves (30 sec; 40° C.). The reaction vessel was drained and a second portion of piperidine/NMP (20percent; 10 ml) was added and heated (75° C.; 3 min.) again. The resin was then washed with DMF (6×10 ml). Side Chain Acylation (0150) Fmoc-Lys(ivDde)-OH or alternatively another amino acid with an orthogonal side chain protective group was introduced at the position of the acylation. The N-terminal of the peptide backbone was then Boc-protected using Boc2O or alternatively by using a Boc-protected amino acid in the last coupling. While the peptide was still attached to the resin, the orthogonal side chain protective group was selectively cleaved using freshly prepared hydrazine hydrate (2-4percent) in NMP for 2×15 min. The unprotected lysine side chain was first coupled with Fmoc-Glu-OtBu or another spacer amino acid, which was deprotected with piperidine and acylated with a lipophilic moiety using the peptide coupling methodology as described above. Alternatively, the acylation moiety was introduced as a premade building block e.g. Fmoc-Lys(hexadecanoyl-gamma-Glu)-OH where gamm-Glu is the coupling of Glutamic acid through the side-chain. Abbreviations employed are as follows: COMU: 1-[(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)-dimethylamino-morpholinomethylene)]methanaminium hexaflourophosphate ivDde: 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)3-methyl-butyl Dde: 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-ethyl DCM: dichloromethane DMF: N,N-dimethylformamide (0151) DIPEA: diisopropylethylamine EtOH: ethanol Et2O: diethyl ether HATU: N-[(dimethylamino)-1H-1,2,3-triazol[4,5-b]pyridine-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide MeCN: acetonitrile NMP: N-methylpyrrolidone (0152) TFA: trifluoroacetic acid TIS: triisopropylsilane Cleavage (0153) The resin was washed with EtOH (3×10 ml) and Et2O (3×10 ml) and dried to constant weight at room temperature (r.t.). The crude peptide was cleaved from the resin by treatment with TFA/TIS/water (95/2.5/2.5; 40 ml, 2 h; r.t.). Most of the TFA was removed at reduced pressure and the crude peptide was precipitated and washed three times with diethylether and dried to constant weight at room temperature. HPLC Purification of the Crude Peptide (0154) The crude peptide was purified to greater than 90percent by preparative reverse phase HPLC using a PerSeptive Biosystems VISION Workstation equipped with a C-18 column (5 cm; 10 mum) and a fraction collector and run at 35 ml/min with a gradient of buffer A (0.1percent TFA, aq.) and buffer B (0.1percent TFA, 90percent MeCN, aq.). Fractions were analyzed by analytical HPLC and MS and relevant fractions were pooled and lyophilized. The final product was characterized by HPLC and MS. (0155) The synthesized compounds are shown in Table 1 and Table 2

References: [1]Patent: US2015/299281,2015,A1 .Location in patent: Paragraph 0147-0155.

4
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 96402-49-2 ]
[ 135248-89-4 ]
[ 116611-64-4 ]
Hy-CAD-[1-Nal]-VCYWHTFG-NH₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Peptide monomers of the present invention were synthesized using the Merrifield solid phase synthesis techniques on Protein Technology's Symphony multiple channel synthesizer. The peptides were assembled using HBTU (0-Benzotriazole-N,N,N',N'-tetramethyl-uronium- hexafluoro-phosphate), Diisopropylethylamine(DIEA) coupling conditions. For some amino acid couplings PyAOP(7-Azabenzotriazol- 1 -yloxy)tripyrrolidinophosponium hexafluorophosphate) and DIEA conditions were used. Rink Amide MB HA resin (100-200 mesh, 0.57 mmol/g) was used for peptide with C-terminal amides and pre-loaded Wang Resin with N-a-Fmoc protected amino acid was used for peptide with C-terminal acids. The coupling reagents (HBTU and DIEA premixed) were prepared at lOOmmol concentration. Similarly amino acids solutions were prepared at 100 mmol concentration. Peptide inhibitors of the present invention were identified based on medical chemistry optimization and/or phage display and screened to identify those having superior binding and/or inhibitory properties.[00611] The peptides were assembled using standard Symphony protocols. The peptide sequences were assembled as follows: Resin (250 mg, 0.14 mmol) in each reaction vial was washed twice with 4ml of DMF followed by treatment with 2.5ml of 20percent 4-methyl piped dine (Fmoc de- protection) for lOmin. The resin was then filtered and washed two times with DMF (4ml) and re -treated with N-methyl piperifine for additional 30 minute. The resin was again washed three times with DMF (4 ml) followed by addition 2.5ml of amino acid and 2.5ml of HBTU-DIEA mixture. After 45min of frequent agitations, the resin was filtered and washed three timed with DMF (4 ml each). For a typical peptide of the present invention, double couplings were performed. After completing the coupling reaction, the resin was washed three times with DMF (4 ml each) before proceeding to the next amino acid coupling.

References: [1]Patent: WO2016/11208,2016,A1 .Location in patent: Paragraph 00610; 00611; 00633.

5
[ 68858-20-8 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 96402-49-2 ]
[ 135248-89-4 ]
[ 116611-64-4 ]
Hy-CADWVCY-[1-NaI]-HTF-OH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Peptide monomers of the present invention were synthesized using the Merrifield solid phase synthesis techniques on Protein Technology's Symphony multiple channel synthesizer. The peptides were assembled using HBTU (0-Benzotriazole-N,N,N',N'-tetramethyl-uronium- hexafluoro-phosphate), Diisopropylethylamine(DIEA) coupling conditions. For some amino acid couplings PyAOP(7-Azabenzotriazol- 1 -yloxy)tripyrrolidinophosponium hexafluorophosphate) and DIEA conditions were used. Rink Amide MB HA resin (100-200 mesh, 0.57 mmol/g) was used for peptide with C-terminal amides and pre-loaded Wang Resin with N-a-Fmoc protected amino acid was used for peptide with C-terminal acids. The coupling reagents (HBTU and DIEA premixed) were prepared at lOOmmol concentration. Similarly amino acids solutions were prepared at 100 mmol concentration. Peptide inhibitors of the present invention were identified based on medical chemistry optimization and/or phage display and screened to identify those having superior binding and/or inhibitory properties.[00611] The peptides were assembled using standard Symphony protocols. The peptide sequences were assembled as follows: Resin (250 mg, 0.14 mmol) in each reaction vial was washed twice with 4ml of DMF followed by treatment with 2.5ml of 20percent 4-methyl piped dine (Fmoc de- protection) for lOmin. The resin was then filtered and washed two times with DMF (4ml) and re -treated with N-methyl piperifine for additional 30 minute. The resin was again washed three times with DMF (4 ml) followed by addition 2.5ml of amino acid and 2.5ml of HBTU-DIEA mixture. After 45min of frequent agitations, the resin was filtered and washed three timed with DMF (4 ml each). For a typical peptide of the present invention, double couplings were performed. After completing the coupling reaction, the resin was washed three times with DMF (4 ml each) before proceeding to the next amino acid coupling.

References: [1]Patent: WO2016/11208,2016,A1 .Location in patent: Paragraph 00610; 00611; 00633.

6
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 71989-20-3 ]
[ 77128-73-5 ]
[ 91000-69-0 ]
[ 116611-64-4 ]
C₁₅₀H₂₂₈N₄₀O₄₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: tGLP-1 and its analogues 2?13 were all synthesized using general solid-phase peptide synthesis of N-Fmoc/tBu chemistry. 63Fmoc Rink Amide-MBHA resin (0.1 mmol) was added to a 25 ml peptide synthetic vessel and swollen with DMF for 40 min. After deprotected by 25percent piperidine in DMF, a solution of Fmoc-AA-OH (0.4 mmol), HATU (0.4 mmol), HoAt (0.4 mmol) and DIPEA (0.8 mmol) in DMF was added to the vessel. After reacted for 1 h, the resin was washed three times with DMF and three times with CH2Cl2, then qualitative ninhydrin testing was performed to monitor whether some free amino groups still existed on the resin ornot. If not, the resin was washed three times with DMF again and repeated the procedures of deprotection and coupling. Forthe coupling of some unnatural amino acids, NMM instead of DIPEA and NMP instead of DMF were used. Besides, the reaction time was prolonged to 4 h. Following the final deprotection of N-terminus, the target peptide was cleaved from resin with Reagent K (TFA/thioanisole/water/phenol/EDT, 82.5:5:5:5:2.5) for 2 h atroom temperature. After filtration, the residue solution was concentrated, precipitated with cold diethyl ether and centrifuged for three times. The residue was dissolved in water and purified by Waters 2545 preparative RP-HPLC system. Sephadex G-25 was used for the further purification to remove some short peptide impurities. The molecular mass of the target peptide was confirmed by MALDI-TOF. The purity of peptide was tested with analytical RP-HPLC, and the conditions were as follows: a linear gradient of 20percent mobile phase A and 80percent mobile phase B to 80percent mobile phase A and 20percent mobile phase B (A: acetonitrile containing 0.1percent TFA; B: H2O containing 0.1percent TFA) in 30 min, at a flow rate of 1 mL/minute with UV detection at 214 nm.

References: [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 1163 - 1170.

7
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 198561-07-8 ]
[ 684270-46-0 ]
C₅₈H₉₀N₂₀O₁₈ [ No CAS ]

References: [1]Chemistry - A European Journal,2016,vol. 22,p. 5534 - 5537.

8
[ 942518-20-9 ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 198561-07-8 ]
C₅₉H₉₂N₂₀O₁₈ [ No CAS ]

References: [1]Chemistry - A European Journal,2016,vol. 22,p. 5534 - 5537.

9
[ 1097192-04-5 ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 198561-07-8 ]
C₆₀H₉₄N₂₀O₁₈ [ No CAS ]

References: [1]Chemistry - A European Journal,2016,vol. 22,p. 5534 - 5537.

10
[ 250695-67-1 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 71989-23-6 ]
[ 73731-37-0 ]
[ 73724-45-5 ]
[ 71989-31-6 ]
[ 125238-99-5 ]
[ 143824-78-6 ]
[ 158599-00-9 ]
N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid [ No CAS ]
C₇₇H₁₁₈N₂₀O₁₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		1. Peptide synthesis 1.1 General synthetic procedures A general method for the synthesis of the peptidomimetics of the present invention is exemplified in the following. This is to demonstrate the principal concept and does not limit or restrict the present invention in any way. A person skilled in the art is easily able to modify these procedures, especially, but not limited to, choosing a different starting position within the ring system, to still achieve the preparation of the claimed cyclic peptidomimetic compounds of the present invention. Coupling of the first protected amino acid residue to the resin . In a dried flask, 2-chlorotritylchloride resin (polystyrene, 1percent crosslinked; loading: 1.4 mMol/g) was swollen in dry CH2CI2 for 30 min (7 mL CH2CI2 per g resin). A solution of 0.8 eq of the Fmoc-protected amino acid and 6 eq of DIPEA in dry CH2CI2/DMF (4/1) (10 mL per g resin) was added. After shaking for 2-4 h at rt the resin was filtered off and washed successively with CH2CI2, DMF, CH2CI2, DMF and CH2CI2. Then a solution of dry CH2CI2/MeOH/DIPEA (17:2:1) was added (10 mL per g resin). After shaking for 3 x 30 min the resin was filtered off in a pre-weighed sinter funnel and washed successively with CH2CI2, DMF, CH2CI2, MeOH, CH2CI2, MeOH, CH2CI2 (2x) and Et20 (2x). The resin was dried under high vacuum overnight. The final mass of resin was calculated before the qualitative control. Loading was typically 0.6 - 0.7 mMol/g. The following preloaded resins were prepared: Fmoc-Dab(Boc)-2-chlorotrityl resin, Fmoc-DDab(Boc)-2-chlorotrityl resin, Fmoc-Lys(Boc)-2-chlorotrityl resin, Fmoc- Trp(Boc)-2-chlortrityl resin, Fmoc-Phe-2-chlortrityl resin; Fmoc-Val-2-chlorotrityl resin, Fmoc-Pro-2-chlorotrityl resin, Fmoc-Arg(Pbf)-2-chlorotrityl resin and Fmoc-Glu(iBu)-2- chlorotrityl resin. Synthesis of the fully protected peptide fragment The synthesis was carried out on a Syro-peptide synthesizer (MultiSynTech GmbH) using 24 to 96 reaction vessels. In each vessel 0.04 mMol of the above resin were placed and the resin was swelled in CH2CI2 and DMF for 15 min, respectively. The following reaction cycles were programmed and carried out: Step Reagent Time 1 CH2CI2, wash and swell (manual) 1 x 3 min 2 DMF, wash and swell 2 x 30 min 3 20percent piperidine/DMF 1 x 5 min and 1 x 15 min 4 DMF, wash 5 x 1 min 5 3.5 eq Fmoc amino acid/3.5 eq HOAt in DMF + 3.5 eq PyBOP/7 eq DIPEA or 3.5 eq DIC 1 x 40 min 6 3.5 eq Fmoc amino acid/DMF + 3.5 eq HATU or PyBOP or HCTU + 7 eq DIPEA 1 x 40 min 7 DMF, wash 5 x 1 min 8 20percent piperidine/DMF 1 x 5 min and 1 x 15 min 9 DMF, wash 5 x 1 min 10 CH2CI2, wash (at the end of the synthesis) 3 x 1 min Steps 5 to 9 are repeated to add each amino-acid residue. After the termination of the synthesis of the fully protected peptide fragment, one of the procedures A - E, as described herein below, was adopted subsequently, depending on which kind of interstrand linkages, as described herein below, were to be formed. Finally, the peptides were purified by preparative reverse phase LC-MS, as described herein below. Procedure A: Cyclization and work up of a backbone cyclized peptide having no interstrand linkage Cleavage, backbone cyclization and deprotection After assembly of the linear peptide, the resin was suspended in 1 mL of 1percent TFA in CH2CI2 (v/v; 0.14 mMol) for 3 minutes. After filtration the filtrate was neutralized with 1 mL of 20percent DI PEA in CH2CI2 (v/v; 1.15 mMol). This procedure was repeated four times to ensure completion of the cleavage. An alternative cleavage method comprises suspension of the resin in lmL of 20percent HFIP in CH2CI2 (v/v; 1.9 mMol) for 30 minutes, filtration and repetition of the procedure. The resin was washed three times with 1 mL of CH2CI2. The CH2CI2 layers containing product were evaporated to dryness. The fully protected linear peptide was solubilised in 8 mL of dry DM F. Then 2 eq of HATU and 2 eq of HOAt in dry DM F (1-2 mL) and 4 eq of DIPEA in dry DM F (1-2 mL) were added to the peptide, followed by stirring for ca. 16 h. The volatiles were removed by evaporation. The crude cyclic peptide was dissolved in 7 mL of CH2CI2 and washed three times with 4.5 mL 10percent acetonitrile in water (v/v). The CH2CI2 layer was then evaporated to dryness. To fully deprotect the peptide, 7 mL of cleavage cocktail TFA/DODT/thioanisol/H20 (87.5 :2.5:5:5) or TFA/TIS/H20 (95:2.5 :2.5) were added, and the mixture was kept for 2.5-4 h at room temperature until the reaction was completed. The reaction mixture was evaporated close to dryness, the peptide precipitated with 7 mL of cold Et20/pentane and finally washed 3 times with 4 mL of cold Et20/pentane. Procedures Bl and B2: Cyclization and work up of a backbone cyclized peptide having a disulfide interstrand linkage Bl: Formation of a disulfide interstrand linkage using DMSO After cleavage, backbone cyclization and deprotection of the linear peptide, as described in the corresponding section of procedure A, th...

References: [1]Patent: WO2016/50361,2016,A1 .Location in patent: Page/Page column 75-80; 88.

11
[ 68858-20-8 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 135248-89-4 ]
[ 125238-99-5 ]
[ 158599-00-9 ]
N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid [ No CAS ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
C₇₅H₁₁₅N₂₃O₁₈S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		1. Peptide synthesis 1.1 General synthetic procedures A general method for the synthesis of the peptidomimetics of the present invention is exemplified in the following. This is to demonstrate the principal concept and does not limit or restrict the present invention in any way. A person skilled in the art is easily able to modify these procedures, especially, but not limited to, choosing a different starting position within the ring system, to still achieve the preparation of the claimed cyclic peptidomimetic compounds of the present invention. Coupling of the first protected amino acid residue to the resin . In a dried flask, 2-chlorotritylchloride resin (polystyrene, 1percent crosslinked; loading: 1.4 mMol/g) was swollen in dry CH2CI2 for 30 min (7 mL CH2CI2 per g resin). A solution of 0.8 eq of the Fmoc-protected amino acid and 6 eq of DIPEA in dry CH2CI2/DMF (4/1) (10 mL per g resin) was added. After shaking for 2-4 h at rt the resin was filtered off and washed successively with CH2CI2, DMF, CH2CI2, DMF and CH2CI2. Then a solution of dry CH2CI2/MeOH/DIPEA (17:2:1) was added (10 mL per g resin). After shaking for 3 x 30 min the resin was filtered off in a pre-weighed sinter funnel and washed successively with CH2CI2, DMF, CH2CI2, MeOH, CH2CI2, MeOH, CH2CI2 (2x) and Et20 (2x). The resin was dried under high vacuum overnight. The final mass of resin was calculated before the qualitative control. Loading was typically 0.6 - 0.7 mMol/g. The following preloaded resins were prepared: Fmoc-Dab(Boc)-2-chlorotrityl resin, Fmoc-DDab(Boc)-2-chlorotrityl resin, Fmoc-Lys(Boc)-2-chlorotrityl resin, Fmoc- Trp(Boc)-2-chlortrityl resin, Fmoc-Phe-2-chlortrityl resin; Fmoc-Val-2-chlorotrityl resin, Fmoc-Pro-2-chlorotrityl resin, Fmoc-Arg(Pbf)-2-chlorotrityl resin and Fmoc-Glu(iBu)-2- chlorotrityl resin. Synthesis of the fully protected peptide fragment The synthesis was carried out on a Syro-peptide synthesizer (MultiSynTech GmbH) using 24 to 96 reaction vessels. In each vessel 0.04 mMol of the above resin were placed and the resin was swelled in CH2CI2 and DMF for 15 min, respectively. The following reaction cycles were programmed and carried out: Step Reagent Time 1 CH2CI2, wash and swell (manual) 1 x 3 min 2 DMF, wash and swell 2 x 30 min 3 20percent piperidine/DMF 1 x 5 min and 1 x 15 min 4 DMF, wash 5 x 1 min 5 3.5 eq Fmoc amino acid/3.5 eq HOAt in DMF + 3.5 eq PyBOP/7 eq DIPEA or 3.5 eq DIC 1 x 40 min 6 3.5 eq Fmoc amino acid/DMF + 3.5 eq HATU or PyBOP or HCTU + 7 eq DIPEA 1 x 40 min 7 DMF, wash 5 x 1 min 8 20percent piperidine/DMF 1 x 5 min and 1 x 15 min 9 DMF, wash 5 x 1 min 10 CH2CI2, wash (at the end of the synthesis) 3 x 1 min Steps 5 to 9 are repeated to add each amino-acid residue. After the termination of the synthesis of the fully protected peptide fragment, one of the procedures A - E, as described herein below, was adopted subsequently, depending on which kind of interstrand linkages, as described herein below, were to be formed. Finally, the peptides were purified by preparative reverse phase LC-MS, as described herein below. Procedure A: Cyclization and work up of a backbone cyclized peptide having no interstrand linkage Cleavage, backbone cyclization and deprotection After assembly of the linear peptide, the resin was suspended in 1 mL of 1percent TFA in CH2CI2 (v/v; 0.14 mMol) for 3 minutes. After filtration the filtrate was neutralized with 1 mL of 20percent DI PEA in CH2CI2 (v/v; 1.15 mMol). This procedure was repeated four times to ensure completion of the cleavage. An alternative cleavage method comprises suspension of the resin in lmL of 20percent HFIP in CH2CI2 (v/v; 1.9 mMol) for 30 minutes, filtration and repetition of the procedure. The resin was washed three times with 1 mL of CH2CI2. The CH2CI2 layers containing product were evaporated to dryness. The fully protected linear peptide was solubilised in 8 mL of dry DM F. Then 2 eq of HATU and 2 eq of HOAt in dry DM F (1-2 mL) and 4 eq of DIPEA in dry DM F (1-2 mL) were added to the peptide, followed by stirring for ca. 16 h. The volatiles were removed by evaporation. The crude cyclic peptide was dissolved in 7 mL of CH2CI2 and washed three times with 4.5 mL 10percent acetonitrile in water (v/v). The CH2CI2 layer was then evaporated to dryness. To fully deprotect the peptide, 7 mL of cleavage cocktail TFA/DODT/thioanisol/H20 (87.5 :2.5:5:5) or TFA/TIS/H20 (95:2.5 :2.5) were added, and the mixture was kept for 2.5-4 h at room temperature until the reaction was completed. The reaction mixture was evaporated close to dryness, the peptide precipitated with 7 mL of cold Et20/pentane and finally washed 3 times with 4 mL of cold Et20/pentane. Procedures Bl and B2: Cyclization and work up of a backbone cyclized peptide having a disulfide interstrand linkage Bl: Formation of a disulfide interstrand linkage using DMSO After cleavage, backbone cyclization and deprotection of the linear peptide, as described in the corresponding section of procedure A, th...

References: [1]Patent: WO2016/50361,2016,A1 .Location in patent: Page/Page column 75-80; 83; 84.

12
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
4-chloro-7-nitro-1,2,3-benzoxadiazole [ No CAS ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 73724-45-5 ]
[ 91000-69-0 ]
[ 116611-64-4 ]
[ 198561-07-8 ]
NBD-HGLASTLTRWAHYNALIRAF-PrA-CONH<SUB>2</SUB> [ No CAS ]

References: [1]RSC Advances,2017,vol. 7,p. 9106 - 9114.

13
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 73724-45-5 ]
[ 91000-69-0 ]
[ 116611-64-4 ]
N-α-Fmoc-L-alanine-3,3,3-d3 [ No CAS ]
[ 198561-07-8 ]
HGLASTLTRWAHYNALIRAF-PrA-CONH<SUB>2</SUB> [ No CAS ]

References: [1]RSC Advances,2017,vol. 7,p. 9106 - 9114.

14
[ 1142-20-7 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
N-(9-fluorenylmethoxycarbonyl)-(L)-5-hydroxy-norvaline-1-allyl ester [ No CAS ]
[ 73731-37-0 ]
[ 77128-73-5 ]
C₄₉H₇₂N₈O₁₂ [ No CAS ]