Polyhydroxylated Cyclopentane β-Amino Acids Derived from d-Mannose and d-Galactose: Synthesis and Protocol for Incorporation into Peptides

A stereoselective synthesis of polyhydroxylated cyclopentane β-amino acids from hexoses is reported. The reaction sequence comprises, as key steps, ring-closing metathesis of a polysubstituted diene intermediate followed by the stereoselective aza-Michael functionalization of the resulting cyclopent-1-ene-1-carboxylic acid ester. Examples of synthesis of polysubstituted 2-aminocyclopentanecarboxylic acid derivatives starting from protected d-mannose and d-galactose are presented. A general protocol for the incorporation of these highly functionalized alicyclic β-amino acids into peptides is also reported.

Characterization of the low energy conformations and differential reactivities of D-glucose and Dmannose based oxepines

Carbohydrate-based oxepines are valuable intermediates for the synthesis of septanose carbohydrates. Here we report the characterization of the preferred conformations of D-glucose and D-mannose based oxepines 1 and 2 using computational chemistry and NMR spectroscopy. Monte Carlo conformational searches on 1 and 2 were performed, followed by DFT optimization and single-point energy calculations on the low energy conformations of each oxepine. Coupling constants were computed for all unique conformations at a B3LYP/6-31G(d,p)u+1s level of theory and weighted based on a Boltzmann distribution. These values were then compared to the experimental values collected using 3JH,H values collected from 1H NMR spectra. Information from the MC/DFT approach was then used in a least squares method that correlated DFT calculated and observed 3JH, H coupling constants.
The conformations of 1 and 2 are largely governed by a combination of the rigidifying enol ether element in combination with the reduction of unfavorable interactions. The vinylogous anomeric effect (VAE) emerged as a consequence, rather than a driver of conformations. Oxepine 1 showed greater reactivity in Ferrier rearrangement reactions relative to oxepine 2, in line with its greater %VAE.

ral Dmannose treatment suppresses experimental autoimmune encephalomyelitis via induction of regulatory T cells

D-mannose (D-m) is a glucose epimer found in natural products, especially fruits. In mouse models of diabetes and airway inflammation, D-m supplementation via drinking water attenuated pathology by modifying cellular energy metabolism, leading to the activation of latent transforming growth factor beta (TGF-β), which in turn induced T regulatory cells (Tregs). Given that Tregs are important in controlling neuroinflammation in experimental autoimmune encephalomyelitis (EAE) and likely in multiple sclerosis (MS), we hypothesized that D-m could also suppress EAE.

D-Mannose

from Bio Basic
MB0554 | 25g: 70.01 EUR

D-Mannose

from MedChemExpress
HY-N0379 | 10mM/1mL: 113.00 EUR

D-(+)-Mannose

from Glentham Life Sciences
GC7397-250G | 250 g: 158.00 EUR

D-(+)-Mannose

from Glentham Life Sciences
GC7397-500G | 500 g: 261.00 EUR

D-(+)-Mannose

from Glentham Life Sciences
GC7397-100G | 100 g: 94.00 EUR

D-(+)-Mannose

from Glentham Life Sciences
GC7397-25G | 25 g: 54.00 EUR

D-(+)-Mannose

from Abbexa
20-abx183971 | [ 100 g: 356.00 EUR ] [ 25 g: 230.00 EUR ] [ 500 g: 926.00 EUR ]

D-Mannose

from Alpha Diagnostics
MAN15-N | 5 g: 286.00 EUR

D-(+)-Mannose, 99%, from wood

from Glentham Life Sciences
GC8181-500G | 500 g: 365.00 EUR

Fmoc-D-Ala-SASRIN resin (200-400 mesh, 0.5-0.8 mmol/g)

from Bachem
D-1425.0001 | 1.0g: 236.00 EUR

Fmoc-D-Ala-SASRIN resin (200-400 mesh, 0.5-0.8 mmol/g)

from Bachem
D-1425.0005 | 5.0g: 841.00 EUR

Boc-D-Ala-PAM resin (200-400 mesh, 0.4-0.7 mmol/g)

from Bachem
D-1495.0001 | 1.0g: 381.00 EUR

Boc-D-Ala-PAM resin (200-400 mesh, 0.4-0.7 mmol/g)

from Bachem
D-1495.0005 | 5.0g: 1421.00 EUR

Boc-D-Asn-PAM resin (200-400 mesh, 0.4-0.7 mmol/g)

from Bachem
D-1570.0001 | 1.0g: 122.00 EUR

Boc-D-Asn-PAM resin (200-400 mesh, 0.4-0.7 mmol/g)

from Bachem
D-1570.0005 | 5.0g: 381.00 EUR

Fmoc-D-Leu-SASRIN resin (200-400 mesh, 0.4-0.7 mmol/g)

from Bachem
D-1765.0001 | 1.0g: 261.00 EUR

Fmoc-D-Leu-SASRIN resin (200-400 mesh, 0.4-0.7 mmol/g)

from Bachem
D-1765.0005 | 5.0g: 925.00 EUR

Fmoc-D-Phe-SASRIN resin (200-400 mesh, 0.4-0.7 mmol/g)

from Bachem
D-1770.0001 | 1.0g: 261.00 EUR

Fmoc-D-Phe-SASRIN resin (200-400 mesh, 0.4-0.7 mmol/g)

from Bachem
D-1770.0005 | 5.0g: 925.00 EUR

Fmoc-D-Val-Wang resin (200-400 mesh, 0.6-0.9 mmol/g)

from Bachem
D-2465.0001 | 1.0g: 176.00 EUR

Fmoc-D-Val-Wang resin (200-400 mesh, 0.6-0.9 mmol/g)

from Bachem
D-2465.0005 | 5.0g: 611.00 EUR

Fmoc-D-Leu-Wang resin (200-400 mesh, 0.50-1.00 mmol/g)

from Bachem
D-2535.0001 | 1.0g: 151.00 EUR

Fmoc-D-Leu-Wang resin (200-400 mesh, 0.50-1.00 mmol/g)

from Bachem
D-2535.0005 | 5.0g: 515.00 EUR

Fmoc-D-Val-SASRIN resin (200-400 mesh, 0.5-0.8 mmol/g)

from Bachem
D-2690.0001 | 1.0g: 145.00 EUR

Fmoc-D-Val-SASRIN resin (200-400 mesh, 0.5-0.8 mmol/g)

from Bachem
D-2690.0005 | 5.0g: 477.00 EUR
We found that D-m delayed disease onset and reduced disease severity in two models of EAE. Importantly, D-m treatment prevented relapses in a relapsing-remitting model of EAE, which mimics the most common clinical manifestation of MS. EAE suppression was accompanied by increased frequency of CD4+FoxP3+ Tregs in the central nervous system, suggesting that EAE suppression resulted from Treg cell induction by D-m. These findings suggest that D-m has the potential to be a safe and low-cost complementary therapy for MS.

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