Neolignan

Neolignans Wood of Machilus obovatifolia SiOj Hx (CHjCy + McjCO CH2CI2 + AcOEt CeS04 + temperature Isolation 76... 

Neolignans Piper hookeri CIS AI2O3 MeOH + H2O Petrol + AcOEt — Isolation 77... 

Zanarotti, A. Synthesis and reactivity of lignin model quinone methides. Biomimetic synthesis of 8.0.4 neolignans. J. Chem. Res., Synop. 1983, 306-307. 

When the alkynyl substrate possesses a nucleophilic functionality, intramolecular solvomercuration reactions can sometimes be observed. These reactions, which result in the formation of a heterocycle, have been used in the total synthesis of natural products. For example, reaction of 114 with Hg(OAc)2 affords the benzofuran derivative 115, which is an important intermediate for the synthesis of various neolignans (Equation (42)).154 155... 

A neolignan isolated by the Merck group from the plant Piperfutokadsurae, was the first natural product discovered as a potent inhibitor of the binding of [3H ]PAF to rabbit platelet membrane preparation with an IC50 close to 0.1 /iM [268]. Named kadsurenone (26), it was also shown to be a specific and potent inhibitor of PAF-induced rabbit platelet aggregation with an IC50 value of 0.99 juM. 

Asatone (110 Scheme 25), a neolignan, was quickly assembled by capitalizing upon the ability of a nucleophilic solvent to intercept the intermediate cation formed upon the electrooxidation of (108) in this instance the conjugated 1,3-diene (109) was produced. This result contrasts with the oxidation of 4,5-dimethoxyphenol (101) (Scheme 23) wherein the nonconjugated 1,4-diene (102) was generated. Diene (109) served admirably as both the diene and the dienophile in an intermolecular Diels-Alder reaction leading to asatone (110) [51]. 

Neolignans are also compounds composed of two phenylpropanoid units, but linked in a manner other than C8-C8 (Fig. 12.1) [10]. The compounds of this class are often chiral and naturally occurring neolignans are usually optically active, which evokes the involvement of DPs in the biosynthesis of neolignans. 

Herein, we briefly outline the recent advances in the studies of stereoselectivity in the biosynthesis of norlignans, lignans, and neolignans. 

Fig. 12.10 Enantioselective formation of neolignans in Vinca rosea and Piper regnellii...

A crude enzyme preparation from Vinca rosea catalyzed the enantioselective coupling of coniferyl alcohol to give rise to an optically active C8-C5 neolignan, dehydrodiconiferyl alcohol, with a ratio of (—)-enantiomer to (+)-enantiomer of 2 1 (Fig. 12.10) [66],... 

Another example of the enzymatic enantioselective formation of a C8-C5 neolignan was reported. A crude enzyme preparation from Piper regnellii catalyzed the enantioselective formation of (+)-conocarpan (85% e.e.) from j9-anol (Fig. 12.10) [67],... 

Incubation of coniferyl alcohol with a crude enzyme preparation from Eucommia ulmoides in the presence of hydrogen peroxide resulted in optically active C8-0-C4 neolignan dimers, (+)-eryf/rro-guaiacylglycerol-( >-coniferyl ether (38% e.e.), and (-)-t/ire<9-guaiacylglycerol- 3-coniferyl ether (34% e.e.) (Fig. 12.11) [68]. In... 

Moss GP (2000) Nomenclature of lignans and neolignans. Pure Appl Chem 72 1493-1523... 

Katayama T, Kado Y (1998) Formation of optically active neolignans from achiral coniferyl alcohol by ceU-free extracts of Eucommia idmoides. J Wood Sci 44 244-246... 

Other examples of the iodonium ylide-based syntheses of furan derivatives involve cycloaddition reactions with alkenes or alkynes. Although the majority of these syntheses involve stable iodonium ylides (86JOC3453 94T11541) (e.g., Eqs. 16 and 17), in some cases the ylides are unstable and are generated in situ (92JOC2135) (e.g., Eq. 18). In the case of alkenes, dihydrofuran derivatives are obtained (Eqs. 16-18). This synthetic route is especially useful for the synthesis of dihydrobenzofuran derivatives that are related to the neolignan family of natural products (Eq. 18). 

Cationic [5 + 2]cycloaddition involving a styrene and p-benzoquinone ketals in the presence of a Lewis acid is the key reaction to a number of neolignans fe nin [187]. The oxygen atoms of the dioxolane function in the cycloaddend rrinforce the a character of their neighboring carbons, and this character is transmitted to the termini which participate in the C-C bond formations. 

Amongst the plant neolignans one finds some 2-methylenetetrahydrofurans of which burchellin (146) (lignan numbering) is an example. In this series the structures, stereochemistry and absolute configurations have been established by a combination of... 

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