Coniferyl alcohol intermediate

The synthesis of tetrahydrofuran derivatives from unsaturated alcohols via hydroformylation intermediates was developed many years ago. Moderate yields are obtained from but-2-en-l,4-diol (Scheme 54)94 but hydroformylation is not the major pathway when coniferyl alcohol is subjected to the oxo process (Scheme 55).9S A more complicated reaction is involved... 

However, the quinone methide (V) allows of a much wider scope of variation. Not only will water (dissociation constant = lO- ) add onto (V) under the normal conditions of lignification via the ionic mechanism shown in Fig. 5, but coniferyl alcohol itself or other phenolic lignin intermediates (dissociation constants of phenols 10" ) will add... 

Coniferyl alcohol guaiacyl ether (XXXIV) has not yet been isolated from the intermediate mixture, but the presence of an ether of this kind must be concluded from the formation of the acid (IX) on treating lignin with alkali, followed by methylation and oxidation 13). Its origin can be explained by combination of Ra and Rd followed by loss of the side chain of Rd. 

The substitution of the phenyl ring necessary for the biosynthesis of coniferyl alcohol (3.79) and sinapyl alcohol (3.81) begins with the hydroxylation of C3. This is a conversion that requires the formation of the ester of /5-coumaroyl-CoA with D-quinate (3.73) or shikimate (3.74) catalyzed by the enzyme hydroxycinnamoyl-CoA shikimate/quinate hydroxy-cinnamoyl transferase (HCT Hoffmann et al., 2003). The hydroxylation of this ester intermediate is catalyzed by the enzyme /i-coumarovl-Co A 3 -hydroxylase (C3 H Schoch et al., 2001 Franke et al., 2002a,b). The resulting shikimate or quinate ester (3.75 3.76) is subsequently hydrolyzed by the same HCT, resulting in caffeoyl-CoA (3.36). 

Irradiation of 2,2-dimethyl chromene through Pyrex using a 550-W Hanovia lamp initiates a retro 4 + 2 reaction to form the extended quinone methide 4, which reacts with methanol to form a pair of methyl ethers (Scheme 6A).18 Flash photolysis of coniferyl alcohol 5 generates the quinone methide 6 (Scheme 6B) by elimination of hydroxide ion from the excited-state reaction intermediate.19 The kinetics for the thermal reactions of 6 in water were characterized,20 but not the reaction products. These were assumed to be the starting alcohol 5 from 1,8-addition of water to 6 and the benzylic alcohol from 1,6-addition of water (Scheme 6). A second quinone methide has been proposed to form as a central intermediate in the biosynthesis of several neolignans,21a and chemical synthesis of neolignans has been achieved... 

Lignin condensation reactions include the formation of diphenylmethanes (57) and (52) and a-carbohydrate ether linkage (55) that may be derived from the quinonemethide (42) [32,277,336-340] or the epoxide (49) [342,343] intermediate. Coniferyl alcohol may be involved in the formation of p-7-linked condensed unit (54) [338,339]. 

Highly reactive quinone methide can be utilized as intermediates in organic synthesis. From the viewpoint of biomimetic synthesis, silybin (782) bearing a benzodioxane skeleton was synthesized in 44.5% yield, together with isosilybin (784) (33.5%), by AgiO-mediated oxidation of equimolar amounts of 27 ,37 -dihydroquercetin (783) and coniferyl alcohol (298) in benzene-acetone. The p-quinone methide 785 must be generated as a reactive intermediate (Scheme 156) °. 

A model system for the synthesis of lignin-like polymers showed that jols would react with the quinone-methlde intermediates in this system by a 1-6 addition (J ). Utilizing this model system, chloroanilines were copolymerized with coniferyl alcohol in the presence of horseradish peroxidase Type II enzyme, hydrogen peroxide, vanillyl alcohol initiator and pH 7.2 buffer (J57). The mechanism of this copolymerization reaction is shown in Equation 36. The... 

G Leary. The Chemistry of Reactive Lignin Intermediates. Parti. Transients in Coniferyl Alcohol Photolysis. J. Chem. Soc. Perkin 11 640-642, 1972. 

K Radotic, J Zakrzewska, D Sladic, and M Jeremic. Study of Photochemical Reactions of Coniferyl Alcohol. I. Mechanism and Intermediate Products of UV Radiation-Induced Polymerization of Coniferyl Alcohol. Photochem. Photobiol. 65 284—291, 1997. 

Lignin, tannins, pigments, and flavor components of spices (cinnamon oil, wintergreen oil, bitter almond, nutmeg, cayenne pepper, vanilla bean, clove, and ginger) are all derived from coniferyl alcohol, which is also the central intermediate in lignin synthesis. 

Most lignans are obtained optically active and, presumably, enantiomerically pure. However, the phenolic coupling processes catalysed by H2C>2-dependent peroxidases, Ch-requiring laccases or phenol oxidases yield racemic products. A protein without an active centre has been isolated that in presence of an oxidase produces stereoselective bimolecular phenoxy radical coupling reactions in in vitro lignan biosynthesis. Its mechanism of action is presumed to involve capture of -coniferyl alcohol-derived free radical intermediates [34],... 

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