Synthesis of (+)-Uniflorine A: A Structural Reassignment and a Configurational Assignment

Abstract

The total synthesis of (+)-uniflorine A has allowed for the structural reassignment and the configurational assignment of the alkaloid (-)-uniflorine A from a 1,2,6,7,8-pentahydroxyindolizidine structure to (-)-(1 R,2 R,3 R,6 R,7 S,7a R)-1,2,6,7-tetrahydroxy-3-hydroxymethylpyrrolizidine (6- epi-casuarine).

Total Synthesis of Calystegine B4

“…The 13 C NMR chemical shifts in D 2 O, however, were all 2.2 ppm upfield from those reported for the natural product. These types of consistent differences in the 13 C NMR spectroscopic data have been noted before for azasugars 11d,11f. The signal of the quaternary carbon atom C‐1 of 20 was not observed but was able to be confirmed by gHMBC correlations.…”

The boronic acid Mannich reaction in alkaloid synthesis

“…The structural reassignment of uniflorine A to 6-epi-casuarine 4 was unequivocally confirmed in 2008 from our total synthesis of (+)-uniflorine A, the enantiomer of the natural product, starting from D-xylose [12]. The NMR spectral data of the synthetic compound matched almost perfectly with that of the natural product.…”

“…The tetrol 7 was readily converted to (-)-uniflorine A 4 by a Mitsunobu cyclization of the amino alcohol 8. A deprotection step then produced (-)-uniflorine A 4 in a total of 11 synthetic steps and 13 % overall yield from L-xylose [12].…”

Asymmetric Domino Reactions Based on the Use of Chiral Substrates

“…The asymmetric Petasis reaction has been applied by Ritthiwigrom et al as the key step in total syntheses of natural products, such as (-)-uniflorine A, 195 and related casuarine, australine and 3-epi-australine, which are biologically active pyrrolizidine alkaloids. 196 All these syntheses employed as key intermediate a chiral tetraol which arose from the asymmetric Petasis L-xylose with allylamine and (E)-styrene boronic acid.…”