Nonchiral-Pool Synthesis of (+)-Hyacinthacine B₁

Abstract

The first nonchiral-pool total synthesis of (+)-hyacinthacine B₁ has been achieved. The synthesis uses as key steps an efficient [2+2] cycloaddition of dichloroketene to a chiral enol ether, two diastereoselective Bruylants-like alkylations, and an effective double Tamao-Fleming oxidation.

Key words

stereoselective synthesis - natural products - azasugars - cycloadditions - double Tamao-Fleming oxidation

References and Notes

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13

Both (R)- and (S)-Stericol^® are now available from Sigma-Aldrich. (S)-Stericol^® was chosen on the basis of previous work [8-¹0] that indicated it would lead to natural hyacinthacine B₁.

14

The lactam was obtained as a 93:7 (^¹H NMR) mixture of diastereomers. The minor enantiomer filtered out over the remainder of the synthesis.

23

The corresponding tetraacetates were also found to be identical by chromatography (TLC) in several different solvent systems and by ^¹H and ^¹³C NMR.