Asymmetric synthesis of aza-diospongin A as an iNOS inducer

The synthesis of the aza-analogue of diospongin A is described. The key steps in the synthetic sequence are Mitsunobu inversion, cross olefin metathesis and intramolecular aza-Michael addition reactions. The biological activity of this new analogue was also evaluated in the induction of nitric oxide synthase and was found to be better when compared to its natural counterpart.

Synthesis of aza-analogue of diospongin A and its biological evaluation in the induction of nitric oxide synthase is described.Figure optionsDownload as PowerPoint slide

(S)-(1-Azidobut-3-enyl)benzeneC10H11N3[α]D25=-92.9 (c 1.0, CHCl3)Source of chirality: Mitsunobu inversionAbsolute configuration: (1S)

(S)-tert-Butyl 1-phenylbut-3-enylcarbamateC15H21NO2[α]D25=-40.5 (c 1.0, CHCl3)Source of chirality: Mitsunobu inversionAbsolute configuration: (1S)

tert-Butyl (1S,3S)-3-hydroxy-1-phenylhex-5-enylcarbamateC17H25NO3[α]D25=-12 (c 1.0, CHCl3)Source of chirality: Mitsunobu inversion, allylationAbsolute configuration: (1S,3S)

tert-Butyl (1S,3S,E)-3-hydroxy-7-oxo-1,7-diphenylhept-5-enylcarbamateC24H29NO4[α]D25=-17 (c 0.25, CHCl3)Source of chirality: Mitsunobu inversion, allylationAbsolute configuration: (1S,3S,E)

2-((2R,4S,6S)-4-Hydroxy-6-phenylpiperidin-2-yl)-1-phenylethanoneC19H21NO2[α]D25=-23.7 (c 1.25, CHCl3)Source of chirality: Mitsunobu inversion, allylation, aza-Michael reactionAbsolute configuration: (2R,4S,6S)