Solid-phase synthesis of selectively protected peptides for use as building units in the solid-phase synthesis of large molecules

Barton, Moira A.; Lemieux, R. U.; Savoie, Jolaine

doi:10.1021/ja00795a006

Cited by 69 publications

(11 citation statements)

References 5 publications

(10 reference 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: 99%

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: 99%

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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“…Such an approach could combine the advantages of the solid-phase and classical methods of peptide synthesis. Among the methods that have been explored for the preparation of protected segments on the solid phase are the use of anchoring bonds that are cleaved by acidolysis (93, 114, 11 5, 117), hydrazinolysis (17,59,80), alcoholysis (6)(7)(8), and photolysis (85,116). However, each of these procedures has inherent problems.…”

Section: For Membranesmentioning

confidence: 99%

Peptides With Affinity for Membranes

Et¹,

Fj²

1987

Annu. Rev. Biophys. Biophys. Chem.

187

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“…59 Thus, halobenzoic acids were anchored to support 1a, converted into biaryl derivatives under Suzuki conditions and cleaved from the resin by treatment with methoxide ion to give a variety of methyl esters. 59 Thus, halobenzoic acids were anchored to support 1a, converted into biaryl derivatives under Suzuki conditions and cleaved from the resin by treatment with methoxide ion to give a variety of methyl esters.…”

Section: Benzylic and Trityl Halidesmentioning

confidence: 99%

Polymer supports for solid-phase organic synthesis

Blackburn

1998

Biopolymers

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The solid‐phase synthesis of small organic molecules has received renewed attention since the first reports of the polymer‐supported synthesis of compounds of therapeutic interest. Solid‐phase synthesis is now a key component of the high‐throughput synthesis and screening approach to drug discovery. The recent rapid growth in the number of organic transformations that have been successfully demonstrated on solid supports has involved both the use of the established amine, halide, and hydroxyl supports developed originally for peptide synthesis, and the design and synthesis of new supports to permit the anchoring and releasing of other functional groups. In this article, resins and linkers are subdivided according to the functional group on the solid support to which the first building block is anchored. The chemistry of these supports is illustrated by a relatively small but representative selection from the many recent examples of potential therapeutic agents synthesized on solid supports. © 1999 John Wiley & Sons, Inc. Biopoly 47: 311–351, 1998

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Solid-phase synthesis of selectively protected peptides for use as building units in the solid-phase synthesis of large molecules

Cited by 69 publications

References 5 publications

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

Peptides With Affinity for Membranes

Polymer supports for solid-phase organic synthesis

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