RU2021106349A - LIQUID PHASE PATHWAYS FOR WNT HEXAPEPTIDES - Google Patents

LIQUID PHASE PATHWAYS FOR WNT HEXAPEPTIDES Download PDF

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RU2021106349A
RU2021106349A RU2021106349A RU2021106349A RU2021106349A RU 2021106349 A RU2021106349 A RU 2021106349A RU 2021106349 A RU2021106349 A RU 2021106349A RU 2021106349 A RU2021106349 A RU 2021106349A RU 2021106349 A RU2021106349 A RU 2021106349A
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otbu
cys
glu
leu
gly
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RU2021106349A
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RU2801268C2 (en
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Деннис ХЕНРИКСЕН
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Внтрисеч Аб
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1. Защищенный пептидный фрагмент Foxy-5 (For-Met-Asp-Gly-Cys-Glu-Leu-ОН), выбранный из:1. Protected peptide fragment Foxy-5 (For-Met-Asp-Gly-Cys-Glu-Leu-OH) selected from: a. PG1-Gly-Cys(PG2)-Glu(OPG3)-Leu-OR1,a. PG 1 -Gly-Cys(PG 2 )-Glu(OPG 3 )-Leu-OR 1 , b. PG1-Asp(OPG3)-Gly-Cys(PG2)-Glu(OPG3)-Leu-OR1,b. PG 1 -Asp(OPG 3 )-Gly-Cys(PG 2 )-Glu(OPG 3 )-Leu-OR 1 , c. PG1 -Met-Asp(OPG3)-Gly-Cys(PG2)-Glu(OPG3)-Leu-OR1,c. PG 1 -Met-Asp(OPG 3 )-Gly-Cys(PG 2 )-Glu(OPG 3 )-Leu-OR 1 , d. For-Met-Asp(OPG3)-Gly-Cys(PG2)-Glu(OPG3)-Leu-OR1,d. For-Met-Asp(OPG 3 )-Gly-Cys(PG 2 )-Glu(OPG 3 )-Leu-OR 1 , где PG1 выбран из H и чувствительных к основанию защитных групп, таких как флуоренилметилоксикарбонил (Fmoc), PG2 выбран из Н и тритила (Trt), PG3 выбран из Н и трет-бутила (tBu), a R1 выбран из Н и С1-С6алкила, такого как метил, этил или трет-бутил (tBu), при условии, что PG1,PG2, PG3 и R1 одновременно не представляют собой водород.where PG 1 is selected from H and base sensitive protecting groups such as fluorenylmethyloxycarbonyl (Fmoc), PG 2 is selected from H and trityl (Trt), PG 3 is selected from H and t-butyl (tBu), and R 1 is selected from H and C 1 -C 6 alkyl such as methyl, ethyl or tert-butyl (tBu), provided that PG 1 , PG 2 , PG 3 and R 1 are not simultaneously hydrogen. 2. Защищенный пептидный фрагмент Foxy-5 (For-Met-Asp-Gly-Cys-Glu-Leu-OH) по п. 1, выбранный из:2. Protected peptide fragment Foxy-5 (For-Met-Asp-Gly-Cys-Glu-Leu-OH) according to claim 1, selected from: a. Fmoc-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 6),a. Fmoc-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 6) b. Fmoc-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 3),b. Fmoc-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 3), c. Fmoc-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu(SEQ ID NO 4),c. Fmoc-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu(SEQ ID NO 4), d. For-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 15).d. For-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 15). 3. Защищенный тетрапептидный фрагмент Foxy-5 по п. 1 или 2 в твердой форме.3. Protected Foxy-5 tetrapeptide fragment according to claim 1 or 2 in solid form. 4. Защищенный тетрапептидный фрагмент Foxy-5 по любому из пп. 1-3 в кристаллической форме.4. Protected tetrapeptide fragment Foxy-5 according to any one of paragraphs. 1-3 in crystalline form. 5. Жидкофазный способ получения защищенного производного Foxy-5 PG1-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu, включающий:5. Liquid-phase method for obtaining a protected derivative of Foxy-5 PG 1 -Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu, including: a. последовательное сочетание трипептида Fmoc-Cys(Trt)Glu(OtBu)-Leu-OtBu (KT-2*) с Fmoc-Gly-OH, Fmoc-Asp-OtBu и PG1-Met, илиa. sequential combination of the tripeptide Fmoc-Cys(Trt)Glu(OtBu)-Leu-OtBu (KT-2*) with Fmoc-Gly-OH, Fmoc-Asp-OtBu and PG 1 -Met, or b. последовательное сочетание тетрапептида Fmoc-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 6) с Fmoc-Asp-OtBu и PG1-Met,b. sequential combination of the tetrapeptide Fmoc-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 6) with Fmoc-Asp-OtBu and PG 1 -Met, где:where: i. снятия защитной группы Fmoc достигают с помощью 1,8-диазабицикло[5,4,0]ундец-7-ена (ДБУ), причемi. Fmoc deprotection is achieved with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), with ii. ДБУ удаляют из реакционной массы перед сочетанием с Fmoc-Asp-OtBu, и причемii. DBU is removed from the reaction mass before combination with Fmoc-Asp-OtBu, and moreover iii. PGi представляет собой чувствительную к основанию защитную группу, такую как Fmoc.iii. PGi is a base sensitive protecting group such as Fmoc. 6. Жидкофазный способ превращения PG1-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu в Foxy-5 (For-Met-Asp-Gly-Cys-Glu-Leu-OH), включающий:6. Liquid-phase method for the conversion of PG 1 -Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu to Foxy-5 (For-Met-Asp-Gly-Cys-Glu-Leu-OH ), including: i. удаление PG1 из гексапептида PG1-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu с последующим сочетанием с муравьиной кислотой с образованием For-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 15),i. removal of PG 1 from hexapeptide PG 1 -Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu followed by coupling with formic acid to form For-Met-Asp(OtBu)-Gly-Cys (Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 15), ii. снятие защиты с For-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 15) с получением Foxy-5 в неочищенной форме,ii. deprotection of For-Met-Asp(OtBu)-Gly-Cys(Trt)-Glu(OtBu)-Leu-OtBu (SEQ ID NO 15) to give Foxy-5 in crude form, а затем:and then: a. необязательную очистку неочищенного продукта с помощью колоночной хроматографии, необязательно с последующим осаждением в виде твердого вещества из органического растворителя,a. optionally purifying the crude product by column chromatography, optionally followed by precipitation as a solid from an organic solvent, b. необязательное осаждение образованного гексапептида Foxy-5 в виде щелочной соли или кислой соли в твердой форме, например, в кристаллической форме.b. optional precipitation of the resulting Foxy-5 hexapeptide as an alkali salt or acid salt in solid form, eg crystalline form.
RU2021106349A 2018-08-20 2019-08-19 Linear liquid pathways for wnt hexapeptides RU2801268C2 (en)

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EP18189699.4 2018-08-20

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RU2801268C2 RU2801268C2 (en) 2023-08-04

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117567566A (en) * 2023-11-28 2024-02-20 山东济肽生物科技有限公司 Liquid phase synthesis process of cyclohexapeptide-9

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117567566A (en) * 2023-11-28 2024-02-20 山东济肽生物科技有限公司 Liquid phase synthesis process of cyclohexapeptide-9
CN117567566B (en) * 2023-11-28 2024-05-03 山东济肽生物科技有限公司 Liquid phase synthesis process of cyclohexapeptide-9

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