8-Hydroxy-menthols

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

Coordination of the aluminum atom of the reducing complex was proposed to take place both to the oxygen atom of the hydroxy group and to the nitrogen atom of the amino group. The asymmetric reduction of enamine perchlorates and ketimines with menthol and bomeol chiral auxiliary reagents (50,51) presumably involves coordination of aluminum to the nitrogen atom of the substrate. 

Emberger and ITopp and Werkhoff and ITopp reported that there are significant sensory differences between the eight menthol and the four menthone enantiomers. (5)(-)-7-Hydroxy-6, 7-dihydrocitronellal has a lily-of-the-valley odor, while the odor of its enantiomer is weaker and has green, leaf like and minty notes.The enantiomers of cis- and trans-Tose oxide have closely similar odors with slight but detectable quality differences. ... 

Dichlorodimethyltitanium, 216 Intramolecular alkylation 9-Bromo-9-phenylfluorene, 48 Chloromethyl ethyl ether, 75 Di-p-carbonylhexacarbonyldicobalt, 99 l-Hydroxy-3-trimethylsilylmethyl-3-butene, 147 Menthol, 172 Potassium t-butoxide, 252 Miscellaneous alkylations at active hydrogens... 

The transformation could also be performed using a chiral enantiopure enol ether as dienophile. The best results were achieved with the isopropenyl ether 182b derived from cheap and commercially available (—)-(lR,2S,5R)-menthol. The cycloadduct was obtained with an endo/exo-selectivity of 4.1 1 and an induced dia-stereoselectivity of 88 12. Treatment of 178b with trifluoroacetic acid/water 19 1 provided (S)-warfarin 175 in an overall yield of 61% referred to 4-hydroxy coumarin 55 and an enantiomeric excess of 76% (HPLC), which could be increased to 95% ee by recrystallization using the purified endo-product 178b as substrate for the hydrolysis. In the same manner (S)-coumachlor 176 and (S)-acenocoumarol 177 were obtained with 56% overall yield and 93% ee and 59% overall yield and 95% ee, respectively. 

Methoxy(tosyloxy)iodo]benzene is obtained from [hydroxy(tosyloxy)iodo]-benzene and trimethyl orthoformate. This iodane has been used for the preparation of the (-)-menthyloxy analog by simple alcohol exchange upon mixing in dichloromethane equimolar quantities of it with (-)-menthol and concentrating under reduced pressure (Scheme 9) [44]. 

Anthraquinones, coumarins, flavonoids, and terpenoids alizarin, anthraflavic acid, bomeol, chrysin, emodin, eugenol, 4-ethylphenol, galangin, 7-hydroxy flavone, menthol (low), 4-methylumbelliferone (low), 1-naphthol, naringen (low),... 

Ammoniumsalz Xll/2, 8 Natriumsalz Xll/2, 7 Hydroxy-menfhyloxy- -Natrium-Salz aus Menthol und phosphorige Saure, danach Natronlauge El, 314 Hydroxy-methoxy- XII/2, 6 El, 322, 325... 

Enantiomers of carboxylic acids may sometimes be separated by GC as methyl esters, but special derivatives are mostly prepared for this purpose. Ackman et al. [188] resolved enantiomers of isoprenoid fatty acids after their conversion into L-menthyl esters. The acids under analysis were chlorinated by refluxing with distilled freshly prepared thionyl chloride and the chlorides produced were treated with L-menthol in the presence of pyridine under strictly anhydrous conditions. GC separation was carried out in a capillary column coated with butanediol succinate polyester. Annett and Stumpf [189] made use of L-menthyloxycarbonyl derivatives for the separation of enantiomers of methyl esters of hydroxy acids. The derivatization reagent, L-menthyl chloroformate, was prepared by the reaction of L-menthol with phosgene, with cooling with ice. Diastereoisomers of different hydroxy acids were thus separated on 1.5% OV-210. 

Other previously described chiral allenyllithiums derived from aminoalcohols 761-764, menthol 765 and sugars 766-7681087 1,189 have been prepared by deprotonation with n-BuLi in ether at —40°C for 15 min. They reacted with carbonyl compounds giving, after hydrolysis, enantioenriched a-hydroxy ketones. 

The cycloaddition reaction of chiral thiocarbonyl 5-oxides derived from terpene alcohols such as (—)-menthol, ( —)-borneol, (+)-a-fenchol and (—)-3-tWo-hydroxy-2-CTitfo-phenylbornane affords 2-substituted 2-alkoxysulfonyl-3,6-dihydro-4,5-dimethyl-2//-thiopyran 1-oxides IIA and 11B as a mixture of diastereomers85. 

The cationic BINAP-Rh complexes catalyze asymmetric 1,3-hydrogen shifts of certain alkenes. Diethylgeranylamine can be quantitatively isomerized in THF or acetone to citronellal di-ethylenamine in 96-99% ee (eq 17). This process is the key step in the industrial production of (-)-menthol. In the presence of a cationic (R)-BINAP-Rh complex, (5)-4-hydroxy-2-cyclopentenone is isomerized five times faster than the (R) enantiomer, giving a chiral intermediate of prostaglandin synthesis. ... 

However, the addition of isoprene (entry 4) reveals a serious lack of regiochemical control under these noncatalyzed reaction conditions. Removal of menthol by methanolysis or hydrolysis (Si02> H2O) afforded enantiomerically pure methoxy- or hydroxy-substituted lactones (424) or (425). Wittig reaction of (425a) provided carboxylic acid (426), a key intermediate for a synthesis of 6,7-dehydroaspidosper-midine. 

B. (5S)-(d-Menthyloxy)-2(5H)-furanone. A 500-mL, round-bottomed flask equipped with a magnetic stirring bar, 10-mL Dean-Stark trap, and reflux condenser is charged with d-menthol (51.9 g, 0.330 mol), 5-hydroxy-2(5H)-furanone (37.3 g, 0.370 mol), D-(-i-)-camphorsulfonic acid (3.96 g, 0.170 mol), and 190 mL of dry benzene (Note 8). The stirred suspension is heated to reflux under argon with an oil bath preheated to 100°C (Note 9). After 1-2 hr, a total of 5.1 mL of water is collected and no residual menthol is apparent by TLC analysis (Note 10). The reaction mixture is cooled in an ice bath and treated carefully with 100 mL of saturated sodium bicarbonate solution. After completion of the addition, stirring is maintained for 90 min as the mixture is allowed to warm to room temperature. The... 

Terpenic compounds are resorbed from the digestive tract and sue situated in the hepatie tissues. Thanks to their ability to dissolve fats, they prevent the formation of cholesterol gathering inside the liver and they also recover proper colloidal state to the bile. Terpenes also enhance the bile content in the hepatic cells and in the liver tracts. Terpenic hydrocarbons dilating the smooth muscles [78, 79] make the hepatic tracts more distended both inside and outside. It has been pointed out that the terpenes contained in Rowachol dissolve bile stones [87-89]. The meehanism of terpenes activity has not as yet been completely explained. It was explained that menthol and other monoterpenes inhibit the activity of the lecithin-cholesterol acyltransferase in the human serum [90]. They also lower the activity of the hepatic S-3-hydroxy-3-methylglutaryl-CoA reductase, which is responsible for the physiological inhibition of cholesterol synthesis in the liver [82, 91, 92]. 

Reaction conditions must be carefully controlled to ensure that these types of substitution reactions proceed through an Sn2 mechanism and inversion occurs at the stereogenic center. In some examples, as with hydroxy groups, this is not a trivial undertaking [1], An example for the inversion of the hydroxy group in menthol that uses dicyclohexylcarbodiimide to activate the hydroxy group (Scheme 5) [6],... 

L-Menthol, hydroxy-dihydro-citronellal, d-and L-citronellol Isomerization of allyl amine with Rh-binap >1000 t/y Takasago [5-7]... 

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