Polymer-bound N-hydroxysuccinimide as a solid-supported additive for DCC-mediated peptide synthesis

Chinchílla, Rafael; Dodsworth, David J.; Nájera, Carmén; Soriano, José Manuel Gómez

doi:10.1016/s0040-4039(01)00763-8

Cited by 29 publications

(22 citation statements)

References 19 publications

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“…71 These studies have been carried out with both HOSu and P-HOSu by choosing different protected (Boc, Cbz, Fmoc) a-amino acids at room temperature in the presence of pyridine as a base in acetonitrile for 6 to 7 hours. Yields (83-98%) were similar for both additives, although in some cases P-HOSu was more effective than HOSu.…”

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confidence: 99%

From α-Amino Acids to Peptides: All You Need for the Journey

Nájera¹

2002

Synlett

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Abstract:In this account several tools necessary for the synthesis of peptides from a-amino acids are considered. Different strategies for the asymmetric synthesis of a-amino acids are studied. New chiral glycine and alanine imines as acyclic and cyclic templates for the asymmetric synthesis of different types of mono as well as dialkylated a-amino acids with acyclic and heterocyclic structures are reviewed. Their diastereoselective alkylation and final hydrolysis takes place under very mild reaction conditions. New polymer-supported cinchonidine and cinchonine ammonium salts and chiral binaphthol-derived aminoalkoxides (BINOLAMs), have been developed as catalysts for the asymmetric PTC alkylation of imino esters. The use of chiral oxazinone and pyrazinone a,b-didehydroamino acid derivatives in hydrogenation, Heck-arylation, cyclopropanation and Diels-Alder cycloaddition reactions for the asymmetric synthesis of a-amino acids are also studied. Azomethine ylides derived from saturated oxazinones can also be used in the asymmetric synthesis of prolines by means of diastereoselective dipolar cycloadditions. For the protection of a-amino acids new efficient reagents, Fmoc-P-OSu and Cbz-P-OSu, derived from poly(styrene-co-N-hydroxymaleimide) named as polymeric N-hydroxysuccinimide (P-HOSu), have been developed. Several new systems such as polymer-supported P-HOSu/DCC and polystyrenebound P-TBTU or P-HBTU, together with non-polymeric thiouronium salts derived from 2-mercaptopyridine-1-oxide and TMU, such as HOTT and TOTT, and from DMPU, such as HODT and TODT, have been used as peptide coupling reagents, in solution and solid phase peptide synthesis, as well as for the preparation of primary amides, Weinreb amides and other hydroxamates, directly from carboxylic acids.

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From α-Amino Acids to Peptides: All You Need for the Journey

Nájera¹

2002

Synlett

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“…8 The activity of the prepared P-HOSu (8) was determined to be 1.0 mmol g -1 by the assay of the OH group content according to the synthesis of the N-isopropylacetamide. 13 The P-HOSu (8) obtained reacted with 4 equiv of the chlorouronium tetrafluoroborate 11a or hexafluorophosphate 11b in the presence of pyridine as base for 24 h at room temperature in acetonitrile as solvent affording P-TSTU (9a) or P-HSTU (9b) as white solids after precipitation with hexane and filtration after (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

“…8 Reagents and solvents from commercial suppliers were used as provided. Analytical TLC was performed with Schleicher & Schuell F1400/LS silica gel plates and the spots were visualized with UV light at 254 nm or by charring with 0.3% ninhydrin.…”

Section: Methodsmentioning

confidence: 99%

“…6 In this context, and in connection with our project on the development of new solid-supported reagents applicable to peptide chemistry, we have prepared polystyrene-bound P-TBTU (7) as an efficient, although rather expensive, polymer-bound peptide coupling reagent. 7 In addition, we have recently developed a co-polymer of polystyrene and maleic anhydride containing the N-hydroxysuccinimide moiety (P-HOSu, 8) 8 which can be easily obtained from an inexpensive commercially available polymer and used as a recoverable racemization-reducing additive for the dicyclohexylcarbodiimide (DCC)-mediated coupling of amino acids. This P-HOSu (8) has also been used for the preparation of polymeric reagents for the protection of amino groups with the 9-fluorenylmethoxycarbonyl (Fmoc), 9 2,7-di-tert-butyl-9-fluorenylmethoxycarbonyl (Dtb-Fmoc), 10 allyloxycarbonyl (Alloc) 11 and propargyloxycarbonyl (Proc) 11 groups.…”

Section: Introductionmentioning

confidence: 99%

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Uronium salts from polymeric N-hydroxysuccinimide (P-HOSu) as new solid-supported peptide coupling reagents

Chinchílla¹,

Dodsworth²,

Nájera³

et al. 2003

Arkivoc

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“…17 Comparison of preparation of C-terminal protected dipeptides in the DCC-mediated reaction shows that polymer-supported HOSu gives almost the same yields with HOSu under similar conditions. 18 Other polymer-supported HOSu derivatives include those prepared using 1,2,3,4-cyclopentanetetracarboxylic dianhydride such as 7, and ammonium and alkylammonium salts (8) (Scheme 4). N-protected amino acids in the presence of triethylamine and 10 mol% 4-dimethylaminopyridine (DMAP) for 45 min at room temperature followed by the addition of amino acids to give di-and tripeptides in 15-98% yields with minimal racemization.…”

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confidence: 99%