Nucleophilic Additions to Cyclic Nitrones en Route to Iminocyclitols – Total Syntheses of DMDP, 6‐deoxy‐DMDP, DAB‐1, CYB‐3, Nectrisine, and Radicamine B

Abstract

Highly diastereoselective nucleophilic additions to cyclic nitrones derived from L-malic acid and D-arabinose have been used for the construction of enantiomerically pure polyhydroxylated pyrrolidines. The synthetic strategy adopted was based on an oxidation/reduction protocol involving hydroxylamine/nitrone pairs and demonstrates the use of reagent-and substrate-derived stereocontrol. In most cases reactions took place with total diastereoselectivity and in quantitative yield, with no purification being necessary. By this strategy, 2-(hydroxymethyl)-, 2-(aminomethyl)-, and 2-aryl-

Recent Developments in the Synthesis of Pyrrolidine‐Containing Iminosugars

“…[21] This work confirmed the previous chemical formulas for codonopsine (5) and codonopsinine (6), however the stereochemistry was corrected to that of the structures shown ( Figure 1). The absolute stereochemistry of the pyrrolidines, radicamine A (7) and B (8), was also recently determined via a series of elegant syntheses [22][23][24] and the absolute stereo-chemistries of the isolated natural products reassigned to those shown ( Figure 1). In 2008, Pyne and co-workers unequivocally proved that uniflorine B, once thought to be an indolizidine, was in fact the known pyrrolizidine alkaloid casuarine (9), and proposed that uniflorine A was in fact 6-epi-casuarine.…”

“…[23,24,82,115,116] The direct diastereoselective addition of dialkyl phosphonates, to yield pyrrolidinylphosphonates, has also been illustrated. [102] Of the pyrrolidines synthesised from cyclic nitrone precursors, perhaps the most common target has been the radicamines A and B.…”

“…[23] A variety of radicamine derivatives were also recently prepared by Goti and co-workers by the combination of nucleophilic addition to a nitrone and a subsequent oxidation/reduction protocol (Scheme 41). [24] In this work, stereoselective addition of phenylmagnesium bromide to the benzyl-protected nitrone 212 yielded hydroxylamine 231, which was subsequently reduced and deprotected to obtain radicamine B (8). This work followed earlier studies by Goti and co-workers, whereby the C-2 epimers of 2-aminomethyl-and 2-hydroxymethyl-3,4-dihydroxypyrrolidines were synthesised by the stereocontrolled addition of TMSCN or LiCH 2 OMOM to a nitrone and subjection of the resulting hydroxylamine to an oxidation-reduction inversion sequence.…”

Straightforward Synthesis of Diverse 1‐Deoxyazapyranosides via Stereocontrolled Nucleophilic Additions to Six‐Membered Cyclic Nitrones

“…[2][3][4] Five-membered cyclic nitrones have been extensively applied in synthetic chemistry, especially for the preparation of pyrrolodine-based molecules. [5][6][7] In our previous reports, [6] we developed a concise method to prepare various azafuranosides, such as DMDP, ADMDP, and their isomers, by using five-membered cyclic nitrones as key intermediates. [6] In contrast, the use of six-membered tri-O-benzyl chiral cyclic nitrones [7][8][9] as key intermediates to study their diastereoselective nucleophilic additions towards the synthesis of 1-deoxyazapyranosides has scarcely been investigated [10b] ( Figure 2).…”

“…[5][6][7] In our previous reports, [6] we developed a concise method to prepare various azafuranosides, such as DMDP, ADMDP, and their isomers, by using five-membered cyclic nitrones as key intermediates. [6] In contrast, the use of six-membered tri-O-benzyl chiral cyclic nitrones [7][8][9] as key intermediates to study their diastereoselective nucleophilic additions towards the synthesis of 1-deoxyazapyranosides has scarcely been investigated [10b] ( Figure 2). Perhaps the systematic preparation of chiral sixmembered cyclic nitrones is not available; thus, their synthetic study and application are limited.…”