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. 2022 Jan 6:18:77-85.
doi: 10.3762/bjoc.18.7. eCollection 2022.

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

İlknur Polat  1 , Selçuk Eşsiz  1   2 , Uğur Bozkaya  3 , Emine Salamci  1
Affiliations

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

İlknur Polat et al. Beilstein J Org Chem. .

Abstract

The first synthesis of 2-amino-3,4-dihydroxycyclooctane-1-carboxylic acid, methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate, and 10-amino-6-hydroxy-8-oxabicyclo[5.2.1]decan-9-one starting from cis-9-azabicyclo[6.2.0]dec-6-en-10-one is described. cis-9-Azabicyclo[6.2.0]dec-6-en-10-one was transformed into the corresponding amino ester and its protected amine. Oxidation of the double bond in the N-Boc-protected methyl 2-aminocyclooct-3-ene-1-carboxylate then delivered the targeted amino acid and its derivatives. Density-functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate was confirmed by X-ray diffraction.

Keywords: DFT; aminocyclitol; azidolysis; bicyclic lactone; bicyclic β-lactam; cyclic β-amino acids.

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Figures

Figure 1
Figure 1
Examples of natural products containing β-amino acids.
Scheme 1
Scheme 1
Synthesis of cyclic β-amino acid 6.
Scheme 2
Scheme 2
Epoxidation of Boc-protected amino ester 4 and hydrolysis of epoxide 7 with HCl(g)–MeOH.
Scheme 3
Scheme 3
Reaction of epoxide 7 with NaHSO4 in methylene chloride/MeOH.
Figure 2
Figure 2
The X-ray crystal structure of 10.
Scheme 4
Scheme 4
Synthesis of cyclic β-amino acid derivative 8.
Scheme 5
Scheme 5
Suggested mechanism for the reaction of epoxide 7 with NaHSO4.
Figure 3
Figure 3
Solvent-corrected relative free energy profile at 298.15 K for the reaction mechanism of 14 shown in Scheme 5.
Figure 4
Figure 4
Solvent-corrected relative free energy profile at 298.15 K for the reaction mechanism of 17 shown in Scheme 5.
Figure 5
Figure 5
The optimized geometries of the conformers 7a and 7b with selected interatomic distances at the B3LYP/6-311++G(d,p) level.
See this image and copyright information in PMC

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