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

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