Stereocontrolled Total Synthesis of Polygalolide A

Abstract

The total synthesis of polygalolide A, a secondary metabolite that was isolated from a Chinese medicinal plant, is reported. A key issue in this synthesis was construction of an oxabicyclo[3.2.1] skeleton, which was solved by the development of an intramolecular Ferrier-type C-glycosylation of a glucal with siloxyfuran as an internal nucleophile. The substrate was prepared from D-glucal by the introduction of trimethylsilylacetylene and siloxyfuran groups. Although C-glycosylation did not occur under the conditions found from model experiments, further examination revealed that the combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,4,6-collidine successfully afforded the desired product as a single diastereomer. The siloxy group at the C3 position played a crucial role in the stereocontrol of this reaction. The product was further transformed into a tetracyclic compound as follows: The vinyl ether and acetylenic moieties were reduced and the siloxy group was removed with a Barton-McCombie reaction. The construction of the six-membered ether and the γ-lactone provided the tetracyclic compound. Finally, a phenolic moiety was introduced by using a Mukaiyama aldol reaction to furnish polygalolide A.

Synthesis of Hexenuloses and a Library of Disaccharides Possessing 3-oxo-glycal Unit

“…(((2R,3R,4S,5S,6S)-3,4-bis(Benzyloxy)-5-iodo-6-methoxytetrahydro-2H-pyran-2-yl)methoxy) (tert-butyl)dimethylsilane (32α). 6-methoxytetrahydro-2H-pyran-4-yl)oxy) (tert-butyl)dimethylsilane (36). Compound 36 was synthesized from (((2R,3R,4R)-3-(benzyloxy)-2-((benzyloxy)methyl)-3,4-dihydro-2Hpyran-4-yl)oxy)(tert-butyl)dimethylsilane 13 (300 mg, 0.68 mmol) by following general procedure A.…”

“…(2S,3R,4S,5R,6R)-5-(Benzyloxy)-4-((tert-butyldimethylsilyl)oxy)-6-(((tert-butyldimethylsilyl)oxy)methyl)-3-iodotetrahydro-2H-pyran-2-yl Acetate (S18). 2,4-di-O-tert-Butyldimethylsilyl-3-O-benzyl Dglucal 36 (1 g, 3.23 mmol) was dissolved in dry CH 2 Cl 2 (15 mL) under nitrogen in a foil-covered round-bottom flask and 4 Å molecular sieves were added, and the solution was stirred for 30 min. To the resulting solution at room temperature was added AcOH (1.8 mL, 32.30 mmol), followed by N-iodosuccinimide (1.09 g, 4.84 mmol).…”

Recent Advances in the Chemical Synthesis of C-Glycosides

“…Introduction of ethynyl groups onto sugar lactones involved nucleophilic addition with lithium (trimethylsilyl)­acetylide in the presence of CeCl 3 and deoxygenation with Et 3 SiH and BF 3 ·OEt 2 ; subsequent desilylation with aqueous NaOH led to β-alkynyl glycosides 595 – 597 in good yields (Scheme ). − …”