Origin of problems related to Staudinger reduction in carbopeptoid syntheses

Abstract

We report the solid phase synthesis of -GG-X-GG-type α/β-carbopeptoids incorporating RibAFU(ip) (1a, tX) or XylAFU(ip) (2a, cX) sugar amino acids. Though coupling efficacy is moderate, both the lengthier synthetic route using Fmoc deriva-tive (e.g., Fmoc-RibAFU(ip)-OH) and the azido deriva-tive (e.g., N 3 -RibAFU(ip)-OH) via Staudinger reaction with nBu 3 P can be successfully applied. Both X-ray dif-fraction, 1 H-and 31 P-NMR, and theoretical (QM) data support and explain why the application of Ph 3 P as Staudinger reagent is "ineffective" in the case of a cis stereoisomer, if cX is attached to the preceding residue with a peptide (-CONH-) bond. The failure of the poly-peptide chain elongation with N 3 -cX originates from the "coincidence" of a steric crowdedness and an electronic effect disabling the mandatory nucleophilic attack dur-ing the hydrolysis of a quasi penta-coordinated triph-enylphosphinimine. Nevertheless, the synthesis of the above α/β-chimera peptides as completed now by a new pathway via 1,2-O-isopropylidene-3-azido-3-deoxy-ribo-and -xylo-furanuronic acid (H-RibAFU(ip)-OH 1a and H-XylAFU(ip)-OH 2a) coupled with N-protected α-amino acids on solid phase could serve as useful examples and starting points of further synthetic efforts.

C-3 epimers of sugar amino acids as foldameric building blocks: improved synthesis, useful derivatives, coupling strategies

“…The rational explanation of the unexpected stability was found in steric repulsions and electronic interactions caused by the relative cis position of the vicinal triphenylphosphinimino group at C-3 and the substituents of C-4. These structural conditions were established by 3D-NMR and X-ray diffraction studies and corroborated by DFT calculations (Csordás 2016).…”

“…The 3-azido-group of compounds 6 and 7 was reduced on two alternative ways: a) hydrogenation in H-Cube® with Pd/C; b) transformation via iminophosphorane (Ph 3 P=N-) under the conditions of Staudinger reaction and subsequent hydrolysis (Csordás 2016). Advantages of the use of H-Cube® continuous-flow reactor instead of the traditional catalytic hydrogenation are the higher yield and the easier separation of the product.…”

Assignment of Vibrational Circular Dichroism Cross‐Referenced Electronic Circular Dichroism Spectra of Flexible Foldamer Building Blocks: Towards Assigning Pure Chiroptical Properties of Foldamers

“…[25,[28][29][30][31][32] (Such ah ydrogen bond was identified in ac lose derivativeb ased on a-d-xylofuranuronamide by X-ray crystallography. [33] )M CMM conformational searches resulted in thousands of conformers, on average, the energetic ordering and population distribution of which was determinedb yD FT calculations.T he most significant conformers are discussed below and grouped according to their basic structural features.…”

“…This hydrogen bond in ATFC fixes and orients the C‐terminal amide plane, as measured by ψ , and thus, effectively reduces the available conformational space of the cyclic β‐amino acid residue . (Such a hydrogen bond was identified in a close derivative based on α‐ d ‐xylofuranuronamide by X‐ray crystallography …”

Approaches to Pyranuronic β‐Sugar Amino Acid Building Blocks of Peptidosaccharide Foldamers

“…By introducing 16 as a common key intermediate, we opened up a new synthetic route to protected forms of both C-4 epimers: 4-amino-4-deoxy-D-glucopyranoside (14) and 4-amino-4-deoxy-D-galactopyranoside (17). The new protocol uses a single starting material 6, and gives both the target -SAAs in good yields.…”