2383 Hikosamine

More recently, Danishefsky reported a fully synthetic route to tunicamin-yluracil (274) derived from tunicamycin (85JA7761) and hikosamine (284) (85JA7762). Cyclocondensation of the ribosederived aldehyde (260) (84JOC1955) (Scheme 35) with diene 259 under catalysis by Eu(fod)3 (83JA3716) afforded an 86% yield of the carbon-linked disaccharide 261. Ozonolysis of 261, followed by oxidative treatment and esterification, furnished the /3-hydroxy ester 262 and its benzyloxymethyl ether 263. 

On the other hand, hikosamine (284), obtained by degradation of hikizimy-cin (285), was synthesized by the recently developed diene-aldehyde cycloaddition reaction (85JA7762). Hexoaldose 278 was synthesized starting with the Eu(fod)3 (83JA3716) mediated cyclocondensation of furfural (275) with diene... 

In a much more complicated piece of work recently disclosed, two stereospecific aldehyde Diels-Alder reactions have been used in preparation of hikosamine derivative 29, a component of the antibacterial compound hizikimycin (Scheme 4-XIII).45k Diene 25 reacted with furfural to give cw-y-pyrone 26, which was transformed in several steps to aldehyde 27. Condensation of 27 with 25 using magnesium bromide as catalyst afforded only adduct 28, presumably via chelated intermediate 27A. Compound 28 was converted in a series of steps to acetylhikosamine 29. The methodlogy described here allowed total synthesis of this unusual sugar having 10 contiguous chiral centers with complete stereocontrol. 

Danishefsky et al. have achieved a synthesis of a methyl peracetyl-oc-hikosaminide (216), an undecose degradation product of the anthelmintic hikizimycin, in which use is twice made of the siloxy-diene aldehyde Diels-Alder reaction. Thus, the reaction between the diene (211) and furfural with [EuCfod) ] catalysis leads to the pyrone (212) which, after elaboration to (213), is again condensed with (211), but this time with magnesium bromide catalysis, which causes addition of the remaining four carbon atoms of the undecose in a chelation-controlled and, notably, a topically exo reaction. Elaboration of (215) to the required protected hikosamine (216) then follows in a straightforward manner. 

---