Info

AgOTfNIS

55%

Scheme 12 Glycosylation of diosgenin with various glucopyranosyl donors.

Scheme 12 Glycosylation of diosgenin with various glucopyranosyl donors.

[TBS or trimethylacetyl (Piv)] was used to monoprotect one of the two hydroxyls of 38. The Piv group was selectively protected at the 3-OH, producing 40 in 64% yield, with the corresponding 2-OPiv product in 9% yield and 2,3-di-OPiv product in 5% yield. The regioselectivity of TBS in this case was moderate, producing 39 in 52% yield with the corresponding 2-OTBS product in 35% yield [19,20].

Glycosylation of diosgenyl disaccharide 44 with monosaccharide trichloroace-timidates (24, 28, 41, 46) produced the corresponding fully protected diosgenyl tri-saccharides (47-50) in excellent yields (84-98%). Cleavage of the benzylidene group under 80% HOAc followed by removal of the acetyl groups under NaOMe provided four series 1 diosgenyl saponins (51-54) (Scheme 14) [19]. Saponin 51 (gracillin), which has been isolated from many medicinal plants, including species of Paris, Dioscoea, and Costacea, was shown to be cardioactive and hemostatic [21,22]. Saponin 52 has been isolated from Ophiopogon, 53 from Taccacheancer, and 54 from Paris [1,16].

Glycosylation of diosgenyl disaccharide 45 with monosaccharide trichloroac-etimidates (41, 46) and thiodisaccharide donors (55-57 ) produced the corresponding fully protected diosgenyl trisaccharides (58, 59) and tetrasaccharides (60-62 ) in good to excellent yields (65-93%). Removal of the acyl groups under NaOH provided the corresponding five series 2 diosgenyl saponins (63-67) (Scheme 15) [20]. Sap-onin 63 (dioscin), which exists widely in plants, including many species intensively used in traditional Chinese herbal medicine, itself exhibits antitumor activity (GI50 = 0.40 ^g/mL against P-388) and antifungal activity [23]. Saponin 64 (polyphyllin D)

Scheme 13 Preparation of the key intermediates 44 and 45. (a) PhCH(OMe)2, 89%. (b) TBSCl, 52%. (c) PivCl, 64%. (d) BF3OEt2, 100%. (e) TBAF, 80%. (f) TsOH, 80%; BzCl, 75%.

Scheme 14 Synthesis of series 1 saponins (51-54 ). (a) BF3OEt2, 84-98%. (b) 80% AcOH; NaOMe, 75-91%.

has been isolated from species of Paris and other genera and shows very promising cardioactive and antitumor properties [21,22]. Saponins 65 and 66 are components of Paris polyphylla [16]. Saponin 67 (balanitin 7) is one of the cytostatic components isolated from the East African medicinal plant Balanites aegyptica, with the ED50 of 0.22 ¡g/mL against P-388 tumor cells [24].

When strategy 2 was used, as long as the steroid has been connected to a sugar moiety, normal chemistry for the oligosaccharide synthesis could be applied to extend the sugar chain. As shown in Scheme 16, a facile "one-pot'' glycosylation protocol [25] was efficiently used: treatment of the thioglycoside acceptor 68 with imidate donors (41 and 34, respectively) and TMSOTf, followed by the addition of diosgenyl disaccharide acceptor 45 and V-iodosuccinimide (NIS), generated the corresponding diosgenyl tetrasaccharides 69 and 70 in excellent yields (96 and 98%, respectively). Deprotection of 69 and 70 produced saponins 65 and 66, respectively [26].

Traditional Chinese Medicine

Traditional Chinese Medicine

Ever wondered what Chinese medicine is all about and whether it works? Thinking about consulting a practitioner but want to know some facts first? Look no further! Here's your chance to purchase an in depth and fully comprehensive eBook on anything and everything to do with this ancient philosophy.

Get My Free Ebook


Post a comment