Synthesis of castanospermine

Abstract

The diastereoselective synthesis of castanospermine is described in 11 synthetic steps from L-xylose. The borono-Mannich reaction between L-xylose, allylamine and (E)-styrene boronic acid gives a tetrahydroxy amine with the desired configurations for C-6, C-7, C-8 and C-8a in the target molecule. A novel pyrrolo[1,2-c]oxazol-3-one precursor was employed to allow for the control of pi-facial diastereoselectivity in an osmium(VIII)-catalysed syn-dihydroxylation (DH) reaction. A regioselective ringopening of the cyclic sulfate derivative of the resulting diol then secured the C-1 hydroxyl group of castanospermine with the correct configuration. A Mitsunobu cyclization then provided di-O-benzyl castanospermine and ultimately the final target alkaloid.

Synthesis of hyacinthacine B3and purported hyacinthacine B7

“…16 Importantly, the pyrrolo [1,2-c]oxazol-3-one 11a has allowed us to secure the desired 1,2-diol configuration of the alkaloid 2, on essentially a trans-2,5-disubstituted-2,5-dihydropyrrole A-ring precursor, that would otherwise be expected to be problematic. O-Benzylation of the diol 12a followed by a chemoselective OPMB deprotection reaction with DDQ gave the secondary alcohol 14a.…”

Recent Developments in the Synthesis of Pyrrolidine‐Containing Iminosugars

“…The RCM methodology used by the Pyne group in the uniflorine work was later exemplified to allow for the syntheses of (-)-swainsonine [81] and castanospermine. [82] In the latter synthesis an RCM on a diene-containing carbamate was a key step. In earlier work, Riera and co-workers also illustrated that deoxymannojirimycin [DMJ (148)] and (-)-swainsonine (10) could be synthesised from enantiomers of the same carbamate precursor 147 (Scheme 27).…”

“…[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.…”

“…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. [117] Scheme 41 Nucleophilic additions to nitrones have also been used in the recent syntheses of a number of pyrrolizidines including (+)-lentiginosine and analogues thereof, [82] and (+)-hyacinthacine A 2 . [118] Key steps in Goti and co-workers lentiginosine synthesis included the diastereoselective addition of vinylmagnesium bromide to a nitrone and RCM, while Valle and co-workers used a SmI 2 -mediated addition to a nitrone and a subsequent SmI 2 -mediated reduction (Scheme 42).…”

Natural Products Containing Medium‐Sized Nitrogen Heterocycles Synthesized by Ring‐Closing Alkene Metathesis

“…In 2008, White et al suggested, therefore, that uniflorine A is 1,2,6,7-tetrahydroxy-3-hydroxymethylpyrrolizidine [36]. [38]. In this case, amino-tetraol 81 had to be protected with three different protecting groups resulting in compound 82.…”