Total Synthesis of 3‐O‐Benzyl‐1,3,5‐tri‐epi‐calystegine B₂ from L‐Sorbose

Abstract

The well known 2,3:4,6‐di‐O‐isopropylidene‐α‐L‐sorbofuranose (12) was chosen as starting material for the synthesis of (1S,4R,5S,6S,7S)‐4‐amino‐6‐benzyloxy‐1,7‐isopropylidenedioxy‐8‐oxabicyclo[3.2.1]octane (33) and (1S,4S,5S,6S,7S)‐4‐amino‐6‐benzyloxy‐1,7‐isopropylidenedioxy‐8‐oxabicyclo[3.2.1]octane (34) through carbon chain‐lengthening at C‐1 and C‐6 by Wittig and magnesium‐mediated alkylation methodology, respectively, followed by ring‐closing olefin metathesis (RCM). These promising oxabicyclic compounds were key intermediates for the preparation of the polyhydroxylated nor‐tropane alkaloid 1,3,5‐tri‐epi‐calystegine B2 (10) as its 3‐O‐benzyl derivative 35. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Recent applications in natural product synthesis of dihydrofuran and -pyran formation by ring-closing alkene metathesis

“…Syntheses of 1,3,5-tri-epi-calystegine B 2 (as its 3-O-benzyl derivative 141), thromboxane B 2 (TXB 2 ) (146) (the stable hydrolysis product of the prostanoid signaling molecule TXA 2 ), and didemniserinolipid B (148) all feature RCM steps leading to bridged DHPs (Schemes 42-44). The strategy to the calystegine RCM substrate 140 (Scheme 42), 55 involved nitrone formation through a sorbose-derived aldehyde condensing with benzylhydroxylamine. The nitrone 139 underwent vinylation and chemoselective reduction, leaving the diene functionality intact.…”

New Reagents for the Synthesis of Arylmethyl Ethers and Esters

“…21 More traditional Williamson ether synthesis led to Hoffman degradation, whereas acidic conditions utilizing benzyl 2,2,2-trichloroacetimidate led to removal of the acid labile groups. Tamayo 22 reported that treatment of alcohol 39 under acidic or basic conditions led to a complicated mixture of products, but treatment with 21 led smoothly to benzyl ether 40 in 72% yield. Inositol 41 could be dibenzylated without the formation of cyclic phosphates that occurred under strongly basic conditions.…”

Recent Advances in the Preparation of Enantiomerically Pure Hydroxylamines from Nitrones

“…[49] The selectivity coul be enhanced by activating the nitrone with TMSOTf and carrying out the reaction at -78ºC (Scheme 8).…”