Dihydroprotolichesterinic acid

The same strategy was also employed in the synthesis of the saturated analogue of protolichesterinic acid ( )-dihydroprotolichesterinic acid (4) can be synthesized using epoxide 32 as a starting material for the intramolecular radical cyclization to yield 33 as the major diastereomer (Scheme 5). Subsequent oxidation gave finally rise to ( )-4, which could be obtained in di-astereomerically pure form by fractional crystallization. 

Mulzer et al. 553) synthesized (-)-nephromopsinic acid by the addition of a chiral allylic bromide to tetradecanal (see Scheme 36). The same group 628, 666) also described total syntheses of (-)- and (+)-roccellaric acid and (-)-dihydroprotolichesterinic acid and secured the relative configuration of (+)-roccellaric acid by an X-ray analysis. One route started from (2S,3E)-l,2-isopropylidene-5-0-benzyl-3-pentene-1,2,5-triol (42) (see Scheme 37). The second route included the ozonisation of methyl-(2RS,3R,4E)-3-benzyloxy-5-hydroxy-oxolan-3-one and subsequent condensation with tridecyltriphenylphosponium bromide (see Scheme 38). Finally they synthesized (-t-)-roccellaric acid and (-l-)-dihydroprotolichesterinic acid from D-glucose as the chiral pool (552) (see Scheme 39). 

Scheme 37. Synthesis of (-)-roccellaric and (-)-dihydroprotolichesterinic acids starting from (2S,3E)-1, 2-isopropylidene-5-0-benzyl-3-pentene-1,2,5-triol...

Scheme 39. Synthesis of (+)-roccellaric acid and (+)-dihydroprotolichesterinic acid...

Mulzer J, Salimi N, Haiti H (1993) First Asymmetric Synthesis of (-1-)- and (-)-Roccellaric Add and Dihydroprotolichesterinic Acid. Tetrahedron Asymmetry 4 457... 

Cp2TiCl-mediated 5-exo-trig cyclizations have been intensively exploited by Roy et al. for the total synthesis of ( )-dihydroprotolichesterinic and ( )-roccellaric acids, ( )-sesamin, ( )-dihydrosesamin, ( )-acuminatin, ( )-eudesmin, ( )-lariciresinol, ( )-pinoresinol, ( )-piperitol, ( )-acumi-natin methyl ether, (zh)-sanshodiol methyl ether, ( )-piperitol methyl ether, ( )-pinoresinol monomethyl ether, ( )-lariciresinol monomethyl ether, and ( )-lariciresinol dimethyl ether [ 100-103]. Moreover, this group has very recently reported the enantioselective synthesis of (-)-sesamin (Scheme 19), (-)-dihydrosesamin, (-)-acuminatin, and (-)-methyl piperitol by radical cyclization of chiral epoxides initiated by Cp2TiCl [104]. 

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