Total Synthesis of Sinenside A

Abstract

The first total synthesis of norlignan glucoside sinenside A has been accomplished. An intramolecular acetalization reaction has been employed as the key skeletal construct to forge the central cyclic disaccharide core. The trans-1,2-diol configuration present in the cyclic disaccharide of this natural product is unique and has been addressed by setting this configuration at the beginning. A 1,2-orthoester group has been selected as a handle for both sp glycosidation and for differentiation of the C2'-OH (that participates in the key acetalization reaction) of the sugar unit.

Structural Elucidation and Total Synthesis of Three 9-Norlignans from Curculigo capitulata

“…3−10 Among them, sinenside A, a novel norlignan glucoside isolated form Curculigo sinensis, 3 has been synthesized. 11 In our current study, three unprecedented 9norlignans, named capitulactones A−C (1−3) (Figure 1) featuring a unique 3,5-dihydrofuro [2,3-d]oxepin-7(2H)-one motif. were isolated from the roots of Curculigo capitulata.…”

“…Capitulactone A (1). It is obtained as a white amorphous powder; [α] D 20 −10.7 (c 0.14, MeOH); 1 H NMR (CDCl 3 ), see Table S1 and 13 C NMR (CDCl 3 ), see Table S1 ((4-Bromo-5-iodo-1,2-phenylene)bis(oxy))bis(tert-butyldimethylsilane) (11). To a solution of compound 10 (30 g, 87.7 mmol) in DCM (100 mL) was added BBr 3 (17.0 mL, 175.4 mmol) slowly over 5 min at 0 °C.…”

“…(Hypoxidaceae) is a herb and widely distributed in the Southern China, and has long been applied in the remedy of traditional Chinese medicine for the treatment of many diseases, such as consumptive cough, kidney asthenia, impotence, and asthma . The previous chemical investigation on the Curculigo species led to the isolation of a number of norlignans, triterpenoids, and other phenolics. − Among them, sinenside A, a novel norlignan glucoside isolated form Curculigo sinensis, has been synthesized . In our current study, three unprecedented 9-norlignans, named capitulactones A–C ( 1–3 ) (Figure ) featuring a unique 3,5-dihydrofuro­[2,3- d ]­oxepin-7­(2 H )-one motif.…”

Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on reaction media

“…as catalyst in dichloromethane at 0 C in the presence of 4Å molecular sieves obtained b-glucoside (630) in good yield (76%) in a 1 h period, which was employed as a key precursor for the synthesis of sinenside A (631) via a multi-step reaction (Scheme 191). 511 The stereoselective O-glycosylation of glycals (632) and glycosylbromides (634) by orthoformates (4,5,127) in the presence of InCl 3 in corresponding solvents (CH 3 CN and CH 2 Cl 2 ) yielded O-glycopyranosides (633, 635) at room temperature (Scheme 192). It must be mentioned that both perbenzyl and peracetyl glycals resulted in 2,3-unsaturated-O-glycosides with major aselectivity while glycosylbromides furnished alkoxy glycosides with high b-selectivity in most cases.…”

“…as catalyst in dichloromethane at 0 °C in the presence of 4 Å molecular sieves obtained β-glucoside (630) in good yield (76%) in a 1 h period, which was employed as a key precursor for the synthesis of sinenside A (631) via a multi-step reaction ( Scheme 191 ). 511 …”