Permethylaryl ethers

The synthetic protocol (Scheme 11.2) toward the flavan-3-ol permethylaryl ethers is based upon the transformation of rc7ro-chalcones into 1,3-diarylpropenes. These compounds are then subjected to asymmetric dihydroxylation to give diarylpropan-l,2-diols that are used as chirons for essentially enantiopure flavan-3-ols. The protocol is demonstrated in Scheme 11.2 for the synthesis of the tetra-(9-methyl-3-(9-acetyl derivatives 61a, 61b, 62a, and 62b of (-l-)-catechin (2), (—)-e 7-catechin, (—)-epicatechin (3), and (+)-e 7-epicatechin (4). ... 

Over the past 10-15 years the development of several studies on the synthesis offlavan-3-ols has progressed. The 4/3-carboxymethylepicatechin, dryopteric acid (39), was recently synthesized via nucleophilic substitution of 4/3-acetoxyepicatechin. " The first stereoselective synthesis of a series of flavan-3-ol permethylaryl ethers, as well as the free phenolic forms, was also developed. This was rapidly followed by the syntheses of C-and other labeled flavan-3-ols. ... 

The synthesis protocol (Scheme 4) toward the flavan-3-ol permethylaryl ethers is based upon the transformation of rrtro-chalcones into 1,3-diarylpropenes. Asymmetric dihydroxylation affords 1,3-diarylpropan-... 

Scheme 6. Proposed route to the cleavage of the interflavanyl bond and of the C-ring in profisetinidins e.g. (24) and permethylaryl ether (68)...

Similar conditions also effected cleavage of the interflavanyl bond in the fisetinidol-(4a-+8)-catechin permethylaryl ether (68) to afford tetra-0-methylcatechin (75) (21%), the l,3-diarylpropan-2-ol (78) (12%), and tri-O-methylfisetinidol (81) (12%). Such a rupture of the interflavanyl bond in the permethylaryl ether (68) introduced an important dimension to these cleavages in relation to the chemistry of the 5-deoxyoligo-flavanoids where the additional chromatographic steps involved with derivatization are often prerequisites for sample purity. The liberation of the chain-terminating flavan-3-ol unit (5) or (75), irrespective of... 

Thus, the formation of the 4P-deuteriofisetinidol- and epifisetinidol derivatives (82) and (87) from the reduction of the profisetinidin permethylaryl ethers (68), (70), and (85) with Na(CN)BD3 in TEA, and of the enantiomer of compound (82) during reduction of the fisetinidol-(4p- 8)-catechin derivative (86), indicated that the deuterium ion is consistently delivered to C(4) of a protonated species of type (73 / 74) from the side opposite to the 2-aryl group of the C-ring. This... 

Scheme 7. Cleavage of the acetal functionality of procyanidin A-1 and A-2 permethylaryl ethers (91) and (92) with Na(CN)BH3 in THF...

The natural occurrence and synthesis of a novel class of C-ring isomerized oligomeric flavanoids, termed phlobatannins, was demonstrated some twelve year ago (111, 112). These 3,4,9,10-tetrahydro-2if,8//-pyrano[2,3-/]chromenes, e.g. (104), are characterized by the liberated resorcinol moieties from the A/C-ring arrangement of the parent biflavanoid, e.g. (24), and by the conspicuous absence of the effects of dynamic rotational isomerism in the NMR spectra of their permethylaryl ether diacetates at ambient temperatures. 

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