Preparation, purification and regioselective functionalization of protoescigenin--the main aglycone of escin complex

Abstract

A two-step chemical process for controlled degradation of escin, affording a mixture of olean-12-ene sapogenins, was elaborated and scaled up. The main component of the mixture--protoescigenin--was isolated and purified, in the form of its corresponding monohydrate, without resource to chromatographic methods. This material was further converted into the high purity 3,24;16,22-di-O,O-isopropylidene derivative in a validated large scale laboratory process.

Scheme 1

Conversion of escin (mixture of saponins) into their aglycons (only protoescigenin and barringtogenol C are shown).

Scheme 2

Original method of preparation of protoescigenin (1) from β-escin (I).

Scheme 3

Technical scheme presenting flow of materials in the escin hydrolysis process, followed by isolation and purification of protoescigenin.

Figure 1

Powder diffractograms of protoescigenin hydrates forms: II (a), III (b), IV (c) and VI (d).

Figure 2

DSC curves of protoescigenin hydrate forms.

Figure 3

The atom labeling scheme of the molecular structure of 1. Thermal displacement ellipsoids are drawn at the 50% probability level.

Scheme 4

Selective isopropylidation of protoescigenin.

Figure 4

The atomic labeling of the molecular structure 2 with ethanol solvent molecule. Thermal displacement ellipsoids are drawn at the 50% probability level.

Figure 5

Overlay of structure 1 (yellow) and 2 (purple). For the clarity of the picture only selected atom labels for structure 2 have been shown.

Figure 6

Crystal packing of molecules of 2—view along the Z axis. The O-H…O hydrogen bond is drawn as green dashed lines.

Figure 7

Structures of 1 and 2.