Alcoholysis of merrifield-type peptide–polymer bonds

Beyerman, H. C.; Hindriks, H.; Leer, E. W. B. De

doi:10.1039/c19680001668

Cited by 22 publications

(13 citation statements)

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“…Inspection of the data in Table 2 leads to the following conclusions: i ) both Boc-and Z-protecting groups may be at the N-terminus, with the latter being somewhat less stable under our transesterification conditions; ii) ester groups in the side-chain of aspartate units also undergo RO exchange (9a+9b); iii) the method is especially well applicable when going from methyl to ethyl or vice uersa and from benzyl to methyl ester; iv) benzyl esters o f peptides cannot be prepared in this way without appreciable epimerization; u ) ally1 ester may (Table I [20], with Et,N/ROH [21], with ion-exchange resins [22], with 2-(dimethylamino)ethanol/TlOEt [23], with KCN/ROH [24], or with titanates [25]. In all these cases, reactions are carried out using either elevated temperatures or long reaction times, and they often provide relatively low yields.…”

Section: )mentioning

confidence: 98%

Transesterifications with 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene/Lithium Bromide (DBU/LiBr) – Also Applicable to Cleavage of Peptides from Resins in Merrifleld Syntheses

Scebach¹,

Thaler

Blaser

et al. 1991

Helvetica Chimica Acta

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(2 1. V. 9 1)A mixture of the amidine base 1,8-diazabicyclo[5,4.0]undec-7-ene (DBU) and LiBr (preferably 0.5 and 5 equiv., resp.) turns out to be a highly efficient catalyst (at 0-25O) for saponifications (in THF/H20) and transesterifications (in ROH). The scope and limitations of the method are determined using ca. two dozens of different ester/alcohol combinations (Schemes 2 and 3 ) . The investigation is focused on peptides as substrates. Under carefully controlled conditions, no epimerization occurs with N-Boc-and N-Z-protected peptide esters, when methyl, ethyl, isopropyl, or ally1 esters are the products, as shown for peptides containing up to six amino acids, with Ala, Leu, MeLeu, Asp(OEt), or Tyr at the C-terminus (Scheme 3 and Tables 1 and 2). Hydrolytic and transesterifying detachments of Boc-Leu-Ala-Gly-Val-OR and Boc-Leu-Ala-Gly-Phe-OR (R = H, Me) from PAM and Wang resins (1-8 h at 0-25", 2 equiv. of DBU, 5 equiv. of LiBr) can be achieved by this method without epimerization of the C-terminal stereogenic center; a comparison with other methods (HF, Ti(OR),) is given (Schemes 4 and 5 ) . Possible protecting-group strategies involving the DBU/LiBr method are discussed (Table 3 ) . Extensive experimental details are given.In the course of our work on olefinations 'A la Horner-Emmons-Wadsworth' [l] with the phosphonate [2] and the highly efficient base system DBU')/LiBr [3] shown in Scheme 1, we noticed that traces of moisture led to rapid hydrolysis of the phosphonate ester at room temperature. Since such esters are normally not readily hydrolyzed, we embarked on a systematic investigation to test, whether saponifications and transesterifications could be generally effected under these conditions.There are numerous methods of achieving transesterifications and ester hydrolyses4) under acidic and basic conditions, with ester-cleaving enzymes'), with titanate@), with ion-exchange resins [8], with KF/crown ether [9], and with distannoxane [lo] to mention

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Section: )mentioning

confidence: 98%

Transesterifications with 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene/Lithium Bromide (DBU/LiBr) – Also Applicable to Cleavage of Peptides from Resins in Merrifleld Syntheses

Scebach¹,

Thaler

Blaser

et al. 1991

Helvetica Chimica Acta

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“…Thus, 2-aminoethanethiol was condensed with glyoxylic acid to give racemic thiazolidine-2-carboxylic acid (24). Treatment of 24 with thionyl chloride and ethanol yielded racemic ethyl thiazolidine-2-carboxylate (25) which was easily resolved using the d-and /-tartaric acids. Previous attempts by us to resolve the primary amide of 24 with the tartaric and di-p-toluoyltartaric acids proved unsuccessful.…”

Section: Resultsmentioning

confidence: 99%

Study of the structural requirements for Dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide

1978

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A number of analogs of the tripeptide L-prolyly-L-leucylglycinamide (1) were synthesized and evaluated in the Dopa potentiation and oxotremorine antagonism tests. The replacement of the glycinamide residue with either the glycine methylamide, glycine, aminoacetonitrile, amino-2-propanone, semicarbazide, or beta-alaninamide residues resulted in a loss of activity in both tests. A 1:1 mixture of L-prolyl-L-leucyl-(-)-thiazolidine-2-carboxamide (8) and L-prolyl-L-leucyl-(+)-thiazolidine-2-carboxamide (9) showed marked activity in the Dopa potentiation test but was unable to antagonize the tremors induced by oxotremorine. L-Prolyl-L-leucyl-L-prolinamide (11), on the other hand, was active in the oxotremorine antagonism test but inactive in the Dopa potentiation test. The replacement of the pyrrolidine ring of 1 with either a thiazolidine or cyclopentane ring system caused a loss of activity. The cyclopentanecarboxylic acid analogue 13, however, was found to have moderate activity in the serotonin potentiation test.

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“…10 g polymer, esterified with 1.57 mmoles/g Boc-Phe , was treated according to [l] successively with Boc-Phe, where Boc-Pro, Boc-Pro, and Boc-Val to give 15 g Bocpentapeptide polymer. The Boc-derivative of Ill was removed from the resin by transesterification with 500 ml methanol, containing 58 g of ethyldiisopropylamine [8]. The methylester Boc-Val-Pro-Pro-Phe-Phe-OMe (TLC on silica gel R,f 0.82 in chloroform-methanol-water (65:25:4), two slower moving impurities) was saponified in 20 ml dimethylformamide by adding 1 N aqueous NaOH at pH 10.9 in an autotitrator.…”

Section: North-holland Fiblishing Company -Amsterdammentioning

confidence: 99%

⁴Phe—⁶Val—antamanide, an antitoxic cyclodecapeptide with C₂ symmetry

1971

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Alcoholysis of merrifield-type peptide–polymer bonds

Cited by 22 publications

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Transesterifications with 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene/Lithium Bromide (DBU/LiBr) – Also Applicable to Cleavage of Peptides from Resins in Merrifleld Syntheses

Transesterifications with 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene/Lithium Bromide (DBU/LiBr) – Also Applicable to Cleavage of Peptides from Resins in Merrifleld Syntheses

Study of the structural requirements for Dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide

⁴Phe—⁶Val—antamanide, an antitoxic cyclodecapeptide with C₂ symmetry

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Alcoholysis of merrifield-type peptide–polymer bonds

Cited by 22 publications

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Transesterifications with 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene/Lithium Bromide (DBU/LiBr) – Also Applicable to Cleavage of Peptides from Resins in Merrifleld Syntheses

Transesterifications with 1,8‐Diazabicyclo[5.4.0]undec‐7‐ene/Lithium Bromide (DBU/LiBr) – Also Applicable to Cleavage of Peptides from Resins in Merrifleld Syntheses

Study of the structural requirements for Dopa potentiation and oxotremorine antagonism by L-prolyl-L-leucylglycinamide

4Phe—6Val—antamanide, an antitoxic cyclodecapeptide with C2 symmetry

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⁴Phe—⁶Val—antamanide, an antitoxic cyclodecapeptide with C₂ symmetry