A simple microscale method for determining the relative stereochemistry of statine units

Abstract

A simple method to determine the relative stereochemistry of statine amino acids (gamma-amino-beta-hydroxyacids) by using (1)H NMR spectroscopy is described. Configurational assignment of statine units within complex natural products is possible without degradation or derivatization as the syn and anti diastereomers can be distinguished by using a combination of chemical shift and coupling constant information derived from the alpha-methylene ABX system. Seventy-three examples are provided, demonstrating the scope and limitations of the methodology. These examples range in complexity from simple statine units to cyclic depsipeptides, such as tamandarin B.

Figure 1

a) Chemical shifts (ppm) for H-3 and H-4 of the syn (blue diamond) and anti (red circle) statine diastereomers. b) Chemical shifts for C-3 and C-4 of the syn (blue diamond) and anti (red circle) statine diastereomers.

Figure 2

Expansions of the H₂-2 ABX systems in the ¹H NMR spectra of two diastereomers (syn & anti). These patterns are essentially mirror images allowing assignment of the relative configuration.

Figure 3

Comparison of the vicinal proton-proton coupling constants between H-2_D and H-3 for the anti (blue diamond) and syn (red circle) diastereomers for compounds 6–24

Figure 4

Expansion of the AB pattern for H₂-2 in the ¹H NMR spectra a) 10b at 300 MHz b) 10b at 800 MHz c) 16b at 300 MHz d) 16b at 800 MHz

Figure 5

a) 300 MHz Spectrum of 16b in CDCl₃ at 300 MHz b) Simulated Spectrum at 300 MHz (δ_Ha 2.426, δ_Hb 2.385, ²J_AB= −15.84, ³J_AX= 0.7 Hz, ³J_BX= 9.3 Hz)

Figure 6

Proposed Conformational Model

Scheme 1

Synthesis of Statine Units.

Scheme 2

Conversion to the Oxazolidine Derivatives.