The Truth about False Unicorn (Chamaelirium luteum): Total Synthesis of 23R,24S‐Chiograsterol B Defines the Structure and Stereochemistry of the Major Saponins from this Medicinal Herb

Abstract

Chamaelirium luteum is used in traditional medicine systems and commercial botanical dietary supplements for the treatment of female reproductive health problems. Despite the wide use of this herb, only very limited phytochemical characterisation is available. Our investigation of C. luteum roots led to the isolation of two new steroidal saponins 1 and 2 that contain an unusual aglycone 3. The absolute configurations of these molecules were unable to be determined spectroscopically and thus the total synthesis of 3 was undertaken and achieved in 16 steps and 1.6 % overall yield from pregnenolone. The key step in the synthesis was the stereoselective installation of the side chain at C-17 and C-20, which employed anion-accelerated oxy-Cope methodology. The relative configuration of aglycone 3 was determined by X-ray crystallography of an advanced synthetic intermediate. The absolute configuration was based upon that of the pregnenolone-derived steroidal skeleton and determined to be 23R,24S.

Reactions of Allylmagnesium Reagents with Carbonyl Compounds and Compounds with C═N Double Bonds: Their Diastereoselectivities Generally Cannot Be Analyzed Using the Felkin–Anh and Chelation-Control Models

“…404 In later studies, it was found that selectivities for the 1,2-addition products were higher when these reagents were transmetalated to form the allylaluminum reagents (Scheme 253). 405 High diastereoselectivity was observed for addition of these reagents from the α-face. These selectivities can be understood by examining the conformation about the enone ring.…”

Caco-2 Monolayer Permeability and Stability of Chamaelirium luteum (False Unicorn) Open-Chain Steroidal Saponins

“…When investigating the open-chain saponins present in C. luteum, Challinor and De Voss reported detailed structural and stereochemical features, in addition to preliminary bioactivity data. ,,− Of the 15 steroidal saponins isolated from false unicorn, eight were novel compounds. Chamaelirosides A and B ( 1 and 2 ), which are based on the same aglycone skeleton, (23 R ,24 S )-chiograsterol B ( 3 ), were predominant …”

Open-chain steroidal glycosides, a diverse class of plant saponins

“…[111][112][113] Another family of open-chain plant glycosides possessing an unusual skeleton are the differently glycosylated chamaelirosides 179-184 based on (23R,24S)-chiograsterol B aglycone (185) and analogous 6-dehydrochamaelirosides 186-189 based on (23R,24S)-chiograsterol A (190). 23,52,118 These saponins all possess oxygenation of positions C-3, C-6, C-16, C-23, and C-24. The hydroxylation of C-3, C-16, and C-24 is shared with the trihydroxy cholesterol glycoside 27 23 that co-occurs in C. luteum; it is clear that they could share a common biosynthetic origin in which the processing of the chamaelirosides and 6-dehydrochamaelirosides is carried forward via oxygenation of positions C-6 and C-23.…”

“…One of the most reliable methods for determination of sidechain stereochemistry is X-ray crystallographic analysis, either of the naturally occurring glycoside 110 or aglycone, 27,51,104 or in combination with total synthesis. 118 The modied (or advanced) Mosher ester analysis has also been used to determine the absolute conguration of C-22 in some glycosides of the alliosterol family, 16,36,45,102,107 although this method suffers from problems of selectivity if more than one secondary alcohol is present in the aglycone.…”