Isovanilline

Many other dihydrochalcones have been made, but most of the toxicological studies have been conducted using NHDC and thus (20) has been petitioned and allowed for use. Neohesperidin is best isolated from the bitter orange (Seville orange), but it can also be synthesized from (18) and isovanillin [621-59-0] (21) (Fig. 7) (98). 

A modification (142) of the synthesis of cryptopleurospermine (159) applied the O-benzoyl cyanohydrin of isovanillin benzyl ether (171) for nucleophilic... 

Degradative studies were carried out on cryptopleurospermine (159) and saxoguattine (160) to complete the structure proof of these alkaloids (136,137). These bases were first reduced to diols 178 and 179, respectively, and then oxidized to produce two aldehydes, isovanillin and compounds 49 or 156 from 159 or 160, respectively. 

The most potent antitumour agent isovanilic isomer la has been synthesized in 11 steps starting from isovanillin 271 (Scheme 49) <2001BML2205>. 

Arizonine (282), a tetrahydroisoquinoline alcaloid, has been recently synthesized in 35% yield from isovanilline, using a photochemical rearrangement like that depicted in Scheme 71. The yield of the photochemical step is 55%, and other byproducts (not shown in Scheme 71) are also formed [200]. The same authors reported the synthesis of caseadine following an analogous procedure. 

Hydroxy-4 methoxy-B-nitrostyrene. This compound is prepared from 3 g of isovanillin and 1.2 ml of nitromethane by using the same method as above, and letting sit for 50 hours. It is reduced as above using 1.3 g of nitrostyrene added over a period of 6 hours to 1.1 g of LAH in 150ml of ether. 

Isovanillin (3-bydroxy-4-methoxybenzaldehyde) [621-59-0] 175°/14mm. Cryst from H2O or CgHg. The oxime has m 147°. 

A more concise route to ( )-cherylline was also devised and commenced with the reductive animation of isovanillin with methylamine followed by reaction of the intermediate benzylamine with vinyl triphenylphosphonium bromide to provide the aminophosphonium salt 619. Sequential treatment of 619 with n-butyllithium and the quinone ketal 615 followed by reaction of the resulting crude allylic amine 620 with boron trifluoride etherate gave the phenolic amine 618 in good overall yield (225). 

LXVII) and benzyl isovanillin (LXVIII) have been obtained with less than one equivalent of aluminum isopropoxide.47 48 With benzalde-hyde 17 an excessnf reagent gives only 55-65% yields of benzyl alcohol... 

The common intermediate in two published biomimetic routes to Lythraceae alkaloids was substituted 4-phenylquinolizid-2-one. In one approach based on a biogenetic hypothesis of Ferris et al. (62), Wrobel and Gol biewski condensed pelletierine (126) with isovanillin (128) and obtained a transfused quinolizidine derivative (130, jS H-5) (64) in 75% yield. A model condensation of pelletierine (126) with benzaldehyde which resulted in a mixture of quinolizidones was reported earlier by Matsunaga et al. (65). In another approach Rosazza et al. (52) condensed A -pjperideine (132) with /J-ketoester 133 to get 134. The next stage in both approaches was reduction of the ketone and esterification or transesterification with derivatives of p-hydroxycinna-mic acid (135 or 136). Investigations into the oxidative coupling of 137 were unsuccessful. 

Methoxyethoxymethyl (MEM)-protected arylquinolizidines 25 and 27 were prepared from MEM-protected isovanillin (29) through the same sequence as shown in Scheme 2. Treatment of the alcohol 28, obtained by basic hydrolysis of 27, with the anhydride 30 gave 31 in 73% yield. Removal of the MEM groups with trifluoroacetic acid in methylene chloride afforded 10-epidemethoxyabreso-line (3) in 12% overall yield from 29. 

The molecular structures of vanillin (4-hydroxy-3-methoxybenzaldehyde), isovanillin (3-hydroxy-4-methoxybenzaldehyde) and ethylvanillin(3-ethoxy-4-hydroxybenzaldehyde) were determined by Egawa et al. (2006) by means of gas electron diffraction. Among them, vanillin and ethylvanillin have a vanilla odour but isovanillin smells different. Vanillin and isovanillin have two stable con-formers and ethylvanillin has four. 

Egawa, T., Kameyama, A. andTakeuchi, H. (2006) Structural determination of vanillin, isovanillin and ethyl-vanillin by means of gas electron diffraction and theoretical calculations. Journal of Molecular Structure 794(1-3), 92-102. 

In one, S-adenosyl-L-methionine was the methyl donor, norepinephrine was the substrate, while products of the reaction, normeranephrine and norparanephrine, were converted to the more stable and more easily obtained compounds vanillin and isovanillin, respectively, by periodate oxidation. The oxidation also allowed for the extraction of the incubation mixture with organic solvents such as ethyl acetate, affording a more complete deproteinization. 

In this study (not shown), the compounds vanillin and isovanillin together with p-hydroxyacetanilide, added as an internal standard, were separated by reversed-phase HPLC (LiChrosorb) with a methanol-50 mM phosphate buffer (pH 7.2) (3 7, v/v) as the mobile phase. The compounds were eluted isocratically and the eluent monitored by an electrochemical detector. 

First the diarylether 158 was prepared by reacting isovanilline with methyl 4-bromobenzoate. 158 was condensed with the phosphonium salt 159 obtained in three steps from the readily available methyl 5-methylisoxazol 3-carboxylate. 

The asymmetric total synthesis of (+)-codeine, the unnatural enantiomer, was accomplished by J.D. White and coworkers using an intramolecular carbenoid insertion as the key step. The first stereogenic center that directed all subsequent stereochemical events was installed by the asymmetric hydrogenation of an alkylidene succinate that was obtained using the Stobbe condensation. Dimethyl succinate and isovanillin were reacted in the presence of excess sodium methoxide at reflux and the resulting reaction mixture was acidified to obtain the monomethyl ester. 

Recently reported SAR studies have demonstrated that the 2-naphthalene moiety is a good surrogate for the isovanillin moiety (4-methoxy-3-hydroxyphenyl), generating highly cytotoxic analogues when combined with the 3,4,5-trimethoxyphenyl or related systems. Fig. (6) [24]. On the other hand, when the naphthalene replaces the 3,4,5-trimethoxy phenyl moiety, the cytotoxic activity is largely decreased. The... 

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