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Chemical Structure| 98115-14-1 Chemical Structure| 98115-14-1

Structure of 98115-14-1

Chemical Structure| 98115-14-1

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Product Details of [ 98115-14-1 ]

CAS No. :98115-14-1
Formula : C15H26N2O7
M.W : 346.38
SMILES Code : [C@H](NC(OC(C)(C)C)=O)(CCC(NC(OC(C)(C)C)=O)=O)C(O)=O
MDL No. :N/A

Safety of [ 98115-14-1 ]

Application In Synthesis of [ 98115-14-1 ]

* 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 [ 98115-14-1 ]

[ 98115-14-1 ] Synthesis Path-Downstream   1~3

  • 1
  • boc-O-benzyl-threonine resin [ No CAS ]
  • [ 13734-41-3 ]
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 2488-15-5 ]
  • [ 13734-34-4 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 23680-31-1 ]
  • [ 73821-95-1 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 47689-67-8 ]
  • [ 47355-10-2 ]
  • [ 65420-40-8 ]
  • [ 98115-14-1 ]
  • [ 20866-46-0 ]
  • His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Ser-Cys-Arg-Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 1 Synthesis of Glucagon Cys17(1-29) and Similar MonoCys Analogs (0283) 0.2mmole Boc Thr(OBzl) Pam resin (SynChem Inc) in a 60ml reaction vessel and the following sequence was entered and run on a modified Applied Biosystems 430A Peptide Synthesizer using FastBoc HBTU-activated single couplings. (0284) HSQGTFTSDYSKYLDSCRAQDFVQWLMNT (SEQ ID NO: 35) The following side chain protecting groups were used: Arg(Tos), Asp(OcHex), Asn(Xan), Cys(pMeBzl), Glu(OcHex), His(Boc), Lys(2Cl-Z), Ser(Bzl), Thr(Bzl), Trp(CHO), and Tyr(Br-Z). The completed peptidyl resin was treated with 20% piperidine/dimethylformamide to remove the Trp formyl protection then transferred to an HF reaction vessel and dried in vacuo. 1.0ml p-cresol and 0.5 ml dimehyl sulfide were added along with a magnetic stir bar. The vessel was attached to the HF apparatus (Pennisula Labs), cooled in a dry ice/methanol bath, evacuated, and aprox. 10ml liquid hydrogen fluoride was condensed in. The reaction was stirred in an ice bath for 1hr then the HF was removed in vacuo. The residue was suspended in ethyl ether; the solids were filtered, washed with ether, and the peptide extracted into 50 ml aqueous acetic acid. An analytical HPLC was run [0.46 x 5 cm Zorbax C8, 1 ml/min, 45C, 214nm, A buffer of 0.1%TFA, B buffer of 0.1%TFA/90%ACN, gradient=10%B to 80%B over 10min.] with a small sample of the cleavage extract. The remaining extract was loaded onto a 2.2 x 25cm Kromasil C18 preparative reverse phase column and an acetonitrile gradient was run using a Pharmacia FPLC system. 5min fractions were collected while monitoring the UV at 214nm (2.0A). A=0.1%TFA, B=0.1%TFA/50%acetonitrile. Gradient = 30%B to 100%B over 450min. (0285) The fractions containing the purest product (48-52) were combined frozen, and lyophilized to give 30.1mg. An HPLC analysis of the product demonstrated a purity of>90% and MALDI mass spectral analysis demonstrated the desired mass of 3429.7. Glucagon Cys21, Glucagon Cys24, and Glucagon Cys29 were similarly prepared.
  • 2
  • [ 15761-39-4 ]
  • [ 13734-41-3 ]
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 2488-15-5 ]
  • [ 13734-34-4 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 23680-31-1 ]
  • [ 73821-95-1 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 47689-67-8 ]
  • [ 47355-10-2 ]
  • [ 65420-40-8 ]
  • [ 98115-14-1 ]
  • [ 20866-46-0 ]
  • HSQGTFTSDYSKYLDSRRAQDFVQWLMNTGPSSGAPPPS [ No CAS ]
YieldReaction ConditionsOperation in experiment
198.1 mg EXAMPLE 2 Synthesis of Glucagon-Cex and Other C-Terminal Extended Analogs. (0286) 285mg (0.2mmole) methoxybenzhydrylamine resin (Midwest Biotech) was placed in a 60ml reaction vessel and the following sequence was entered and run on a modified Applied Biosystems 430A peptide synthesizer using FastBoc HBTU-activated single couplings. (0287) HSQGTFTSDYSKYLDSRRAQDFVQWLMNTGPSSGAPPPS (SEQ ID NO: 36) The following side chain protecting groups were used: Arg(Tos), Asp(OcHex), Asn(Xan), Cys(pMeBzl), Glu(OcHex), His(Boc), Lys(2Cl-Z), Ser(Bzl), Thr(Bzl), Trp(CHO), and Tyr(Br-Z). The completed peptidyl resin was treated with 20% piperidine/dimethylformamide to remove the Trp formyl protection then transferred to HF reaction vessel and dried in vacuo. 1.0ml p-cresol and 0.5 ml dimehyl sulfide were added along with a magnetic stir bar. The vessel was attached to the HF apparatus (Pennisula Labs), cooled in a dry ice/methanol bath, evacuated, and aprox. 10ml liquid hydrogen fluoride was condensed in. The reaction was stirred in an ice bath for 1hr then the HF was removed in vacuo. The residue was suspended in ethyl ether; the solids were filtered, washed with ether, and the peptide extracted into 50 ml aqueous acetic acid. An analytical HPLC was run [0.46 x 5 cm Zorbax C8, 1 ml/min, 45C, 214nm, A buffer of 0.1%TFA, B buffer of 0.1%TFA/90%ACN, gradient=10%B to 80%B over 10min.] on an aliquot of the cleavage extract. The extract was loaded onto a 2.2 x 25cm Kromasil C18 preparative reverse phase column and an acetonitrile gradient was run for elution using a Pharmacia FPLC system. 5min fractions were collected while monitoring the UV at 214nm (2.0A). A=0.1%TFA, B=0.1%TFA/50%acetonitrile. Gradient = 30%B to 100%B over 450min. Fractions 58-65 were combined, frozen and lyophilized to give 198.1mg. (0288) HPLC analysis of the product showed a purity of greater than 95%. MALDI mass spectral analysis showed the presence of the desired theoretical mass of 4316.7 with the product as a C-terminal amide. Oxyntomodulin and oxyntomodulin-KRNR were similarly prepared as the C-terminal carboxylic acids starting with the appropriately loaded PAM-resin.
  • 3
  • [ 13734-41-3 ]
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 2488-15-5 ]
  • [ 13734-34-4 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 23680-31-1 ]
  • [ 73821-95-1 ]
  • [ 123417-18-5 ]
  • [ 84624-27-1 ]
  • [ 47689-67-8 ]
  • [ 47355-10-2 ]
  • [ 83468-83-1 ]
  • [ 65420-40-8 ]
  • [ 98115-14-1 ]
  • HSQGTFTSDYSKYLDERRAQDFVQWLMNT-NH2, lactam 12-16 [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 11 Synthesis of Glucagon Lactams (0299) 285 mg (0.2 mmole) methoxybenzhydrylamine resin (Midwest Biotech) was added to a 60 mL reaction vessels and the following sequence was assembled on a modified Applied Biosystems 430A peptide synthesizer using Boc DEPBT-activated single couplings. HSQGTFTSDYSKYLDERRAQDFVQWLMNT-NH2 (12-16 Lactam; SEQ ID NO: 12) (0300) The following side chain protecting groups were used: Arg(Tos), Asp(OcHx), Asn(Xan), Glu(OFm), His(BOM), Lys(Fmoc), Ser(Bzl), Thr(Bzl), Trp(CHO), Tyr(Br-Z). Lys(Cl-Z) was used at position 12 if lactams were constructed from 16-20, 20-24, or 24-28. The completed peptidyl resin was treated with 20% piperidine/dimethylformamide for one hour with rotation to remove the Trp formyl group as well as the Fmoc and OFm protection from Lys12 and Glu16. Upon confirmation of removal by a positive ninhydrin test, the resin was washed with dimethylformamide, followed by dichloromethane and than again with dimethylformamide. The resin was treated with 520 mg (1 mmole) Benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP) in dimethylformamide and diisopropylethylamine (DIEA). The reaction proceeded for 8-10 hours and the cyclization was confirmed by a negative ninhydrin reaction. The resin was washed with dimethylformamide, followed by dichloromethane and subsequently treated with trifluoroacetic acid for 10 minutes. The removal of the Boc group was confirmed by a positive ninhydrin reaction. The resin was washed with dimethylformamide and dichloromethane and dried before being transferred to a hydrofluoric acid (HF) reaction vessel. 500 muL p-cresol was added along with a magnetic stir bar. The vessel was attached to the HF apparatus (Peninsula Labs), cooled in a dry ice/methanol bath, evacuated, and approximately 10 mL of liquid hydrofluoric acid was condensed into the vessel. The reaction was stirred for 1 hour in an ice bath and the HF was subsequently removed in vacuo. The residue was suspended in ethyl ether; the solids were filtered, washed with ether, and the peptide was solubilized with 150 mL 20% acetonitrile/1% acetic acid. (0301) An analytical HPLC analysis of the crude solubilized peptide was conducted under the following conditions [4.6 X 30 mm Xterra C8, 1.50 mL/min, 220 nm, A buffer 0.1% TFA/10% ACN, B buffer 0.1% TFA/100% ACN, gradient 5-95%B over 15 minutes]. The extract was diluted twofold with water and loaded onto a 2.2 X 25 cm Vydac C4 preparative reverse phase column and eluted using an acetonitrile gradient on a Waters HPLC system (A buffer of 0.1% TFA/10% ACN, B buffer of 0.1% TFA/10% CAN and a gradient of 0-100% B over 120 minutes at a flow of 15.00 ml/min. HPLC analysis of the purified peptide demonstrated greater than 95% purity and electrospray ionization mass spectral analysis confirmed a mass of 3506 Da for the 12-16 lactam. Lactams from 16-20, 20-24, and 24-28 were prepared similarly.
 

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