(Fluoren-9-ylmethoxy)carbonyl (Fmoc) amino acid azides: Synthesis, isolation, characterisation, stability and application to synthesis of peptides

Babu, Vommina V. Suresh; Ananda, K.; Vasanthakumar, Ganga-Ramu

doi:10.1039/b006756n

Cited by 20 publications

(7 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A variety of N-acylation methods has been developed for use in peptide synthesis; in particular, the activation of the acid by carbodiimides [19], phosphonium reagents [20], uronium reagents [21] or the use of the corresponding acid fluorides [22,23] acid azides [24] or acid chlorides [25].…”

mentioning

confidence: 99%

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Harwood

Mountford

Yan

2008

Journal of Peptide Science

View full text Add to dashboard Cite

3-Substituted-5-phenylmorpholinones have been demonstrated to act as N-protected C-terminus activated alpha-amino acids capable of undergoing solution phase N-terminus peptide extension following standard coupling procedures. The N-acylated morpholinones do not undergo epimerisation of the stereocentre of the C-terminus amino acid residue as oxazolone formation is sterically prevented, although C-terminus peptide coupling is still possible. This convergent approach to peptide synthesis is exemplified by the preparation of L-ala-L-ala-L-ala and L-ala-D-ala-L-ala.

show abstract

mentioning

confidence: 99%

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Harwood

Mountford

Yan

2008

Journal of Peptide Science

View full text Add to dashboard Cite

show abstract

“…Fmoc-peptide acids 1a-q 32,33 were converted to the corresponding acid azides by employing the standard procedures. As demonstrated by us in the case of N R -Fmoc-amino acid azides, 34 all the N R -Fmoc-peptide acid azides 2a-q prepared were isolated as shelf-stable crystalline solids and fully characterized before use. They were then subjected to Curtius rearrangement (Scheme 1) by refluxing the toluene solution at 65 °C.…”

Section: Resultsmentioning

confidence: 99%

Preparation, Isolation, and Characterization ofN^α-Fmoc-peptide Isocyanates: Solution Synthesis of Oligo-α-peptidyl Ureas

2006

View full text Add to dashboard Cite

The N(alpha)-Fmoc-peptide isocyanates 3a-q, 4a-c, and 5a-c were prepared by the Curtius rearrangement of N(alpha)-Fmoc-peptide acid azides in toluene under thermal, microwave, and ultrasonic conditions. All the N(alpha)-Fmoc-oligo-peptide isocyanates made were isolated as stable crystalline solids with 71 to 94% yield and were fully characterized by 1H NMR, 13C NMR, and mass spectroscopy. Their utility for the synthesis of oligo-alpha-peptidyl ureas 7a-f and 8a-c by the divergent coupling approach was demonstrated. The coupling of N(alpha)-Fmoc-dipeptide isocyanates with amino acid ester or with N,O-bis(trimethylsilyl)amino acids resulted in N(alpha)-Fmoc-tripeptidyl urea ester and acids containing one each of peptide bond and urea bond. The divergent approach is extended to the synthesis of tetrapeptidyl ureas by the 2 + 2 strategy using bis-TMS-peptide acid as an amino component. To incorporate urea bonds in adjacent positions, N(alpha)-Fmoc-peptidyl urea isocyanates 9a-d were prepared and employed in the synthesis of three tetrapeptidyl ureas 10a-b and 11 containing one peptide bond and two urea bonds in series from the N-terminal end. The protocol was then employed for the synthesis of five urea analogues 13-15, 18, and 21 of [Leu5]enkephalin containing urea bonds at the 2, 3, 4 positions as well as at the 2, 4 and 2, 3, 4 positions. The analogue 2l was made by the convergent synthesis by the N --> C terminal chain extension. Finally, two urea analogues 22 and 23 of repeat units of bioelasto polymers, namely Val-Pro-Gly-Val-Gly-OH and Pro-Gly-Val-Gly-Val-OH, were synthesized incorporating the urea bond by the concomitant isocyanate generation and urea bond formation under thermal conditions.

show abstract

“…N-Boc-protected glycine was converted to the Boc-protected aminomethyl isocyanate 10 in very good overall yield by adaptation of the reported preparation of Fmoc-protected aminomethyl isocyanate. 14 Interaction of isocyanate 10 with diazo-IC 3 in DMSO afforded the Boc-protected 3-(aminomethyl)imidazotetrazinone 11 in 63% yield. Deprotection of compound 11 under acidic conditions did not lead to the N-3 aminomethyl salt 12, but to a product which had spectroscopic properties ( 1 H, 13 C, 15 N NMR, ESIMS, IR and UV) 15 consistent with the structure of nor-temozolomide.…”

Section: Synthesis Of Nor-temozolomidementioning

confidence: 99%

Antitumour imidazotetrazines. Synthesis and chemistry of 4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide (nor-temozolomide): an intermediate for the preparation of the antitumour drug temozolomide and analogues, avoiding the use of isocyanates

2012

View full text Add to dashboard Cite

show abstract

(Fluoren-9-ylmethoxy)carbonyl (Fmoc) amino acid azides: Synthesis, isolation, characterisation, stability and application to synthesis of peptides

Cited by 20 publications

References 19 publications

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Preparation, Isolation, and Characterization ofN^α-Fmoc-peptide Isocyanates: Solution Synthesis of Oligo-α-peptidyl Ureas

Antitumour imidazotetrazines. Synthesis and chemistry of 4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide (nor-temozolomide): an intermediate for the preparation of the antitumour drug temozolomide and analogues, avoiding the use of isocyanates

Contact Info

Product

Resources

About

(Fluoren-9-ylmethoxy)carbonyl (Fmoc) amino acid azides: Synthesis, isolation, characterisation, stability and application to synthesis of peptides

Cited by 20 publications

References 19 publications

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Morpholinone mediated oxazolone‐free C‐terminus amide coupling permitting a convergent strategy for peptide synthesis

Preparation, Isolation, and Characterization ofNα-Fmoc-peptide Isocyanates: Solution Synthesis of Oligo-α-peptidyl Ureas

Antitumour imidazotetrazines. Synthesis and chemistry of 4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide (nor-temozolomide): an intermediate for the preparation of the antitumour drug temozolomide and analogues, avoiding the use of isocyanates

Contact Info

Product

Resources

About

Preparation, Isolation, and Characterization ofN^α-Fmoc-peptide Isocyanates: Solution Synthesis of Oligo-α-peptidyl Ureas