A Glycal Approach to the Synthesis of Pregnane Glycoside P57

Abstract

Pregnane glycoside P57 is known as an active component of Hoodia gordonii, which has long been used as a diet with appetite suppressant property. Chemical synthesis of P57 demands installation of β-cymarosyl linkage onto the steroid aglycone. The stereoselective formation of this special 2-deoxy-β-glycosidic linkage has previously been proven to be difficult and thus a limiting step in the synthesis of P57 and its congeners. Herein, we report the glycosylation reactions with glycals as donors and TPHB (triphenylphosphine hydrobromide) as promoter and a convergent synthesis of P57 via a β-selective glycosylation with a trisaccharide glycal donor.Scheme 1 Prepartion of cymarosyl glycals 5-7 www.cjc.wiley-vch.de

Merging total synthesis and NMR technology for deciphering the realistic structure of natural 2,6-dideoxyglycosides

“…in CHCl 3 at −40°C; subsequent desilylation with TBAF at 60°C facilitated the purification of the resulting glycoside anomers, providing the proposed ecdysantheroside A ( 3a ) in satisfactory yield and stereoselectivity (97% over two steps, β/α = 3.9:1). It was known that the bulky TBDPS group at O 4 could enhance the β selectivity in glycosylation with cymarosyl donors via shielding the α face of the oxycarbenium intermediate ( 51 – 53 ). By the same token, coupling of d -cymarosyl o -hexynylbenzoate 18 with ecdysantherin ( 2 ), followed by desilylation with TBAF in the presence of acetic acid furnished ecdysoside A ( 5 ) (60% over two steps, β).…”

“…The convergent assembly of pregnane trisaccharides 4a and 6a called for glycosylation of the aglycones with the corresponding trisaccharide o-hexynylbenzoates (i.e., 19 and 20) (51)(52)(53). We screened various combinations of the gold(I) catalyst, solvent, and temperature for the coupling of aglycone 1 with trisaccharide donor 19 (see table S2 for details).…”

2-Diphenylphosphinoyl-acetyl as a remote directing group for the highly stereoselective synthesis of β-glycosides

“…15,16 Owing to the anomeric effect, glycosylation with 2-deoxy-or 2-azido-2-deoxy-glycosyl donors tends to give -glycosides as the major product. 3,4,10 Thus, extensive studies have been devoted into the construction of the more challenging -glycosides, [8][9][10][11][12][13][14] employing donors/intermediates via SN2/SN2-like pathway, [17][18][19][20] -face steric hindrance, [21][22][23][24] 2-halo participation, 25,26 -glycosyl lithium, 27,28 triflate acceptor, 29 2,3-anhydrosugar, 30 de novo synthesis, 31,32 oxidative activation with I2, 33 etc. However, their application in complex carbohydrate synthesis was usually case by case, hampered by narrow substrate scope, low efficiency, tedious steps, or harsh conditions.…”