D-Isomenthol

Esters of pyromellitic acid. Part II. Esters of chiral alcohols: para pyromellitate diesters as a novel class of resolving agents and use of pyromellitates as duplicands for chiral purification.[Pubmed:18522418]

J Org Chem. 2008 Jul 4;73(13):4939-48.

Methods are presented for the preparation of pyromellitate esters of chiral terpene alcohols, including d- (3) or l-menthol (4), D-Isomenthol (7), l-borneol (8), or d- (5) or l-isopinocampheol (6). Alcoholysis of PMDA in CH2Cl2/Et3N led to the formation of monoesters (e.g., 18) or diesters (11, 12), as needed, relying on the differential reactivity of the two anhydride groups. The easily isolated para diester (11) crystallized before the meta diester (12) from HOAc. Nicotine (1, 14) was efficiently resolved as 1:1 salts with the menthyl (11a, 11b) or bornyl (11f) para diesters, prototypes of what promises to be a large class of novel resolving agents. Recrystallization of para-di-d-menthyl pyromellitate (11a) greatly improved the chiral purity of the contained d-menthol (3), an example of purification by "duplication". An alternative synthesis of specific diesters took advantage of the easily separated benzyl diesters and their derived acid chlorides (19, 21), with the benzyl esters serving as temporary blocking groups removable by catalytic hydrogenolysis. Pyromellitate tetraesters (26) were prepared by base-catalyzed transesterification of the tetraethyl ester (25). Tri- l-menthyl pyromellitate (27b) was obtained by catalytic hydrogenolysis of benzyl tri-l-menthyl pyromellitate (31b), itself prepared from the alcoholysis of benzyl pyromellitate triacid chloride (30) with l-menthol (4).

Effect of l-menthol on laryngeal receptors.[Pubmed:2022571]

J Appl Physiol (1985). 1991 Feb;70(2):788-93.

We have studied the effect of l-menthol on laryngeal receptors. Experiments have been conducted in 11 anesthetized dogs that breathed through a tracheostomy. We have recorded the activity of 23 laryngeal cold receptors and 19 mechanoreceptors. Constant flows of air, 15-50 ml/s (low) and 100-150 ml/s (high), passing for 10 s through the isolated upper airway in the expiratory direction, lowered laryngeal temperature and activated the cold receptors. This cold-induced discharge promptly ceased upon withdrawal of the airflow. Addition of l-menthol to the airflow evoked, for a similar decrease in temperature, a greater peak activation of the cold receptors than airflow alone (low flows 164%, high flows 111%); statistical significance was reached only for the lower flow. This activity outlasted the cessation of airflow by 30-120 s, even at a time when laryngeal temperature had returned to control (low flow 237%, high flow 307% of similar trials with airflow alone). Four laryngeal cold receptors were also tested with l-menthol added to a warm, humidified airflow that did not change laryngeal temperature; all of them were stimulated with a long-lasting discharge. Nine cold receptors were also tested with d-neomenthol and D-Isomenthol; both isomers stimulated the receptors. None of the 19 mechano-receptors tested was affected by l-menthol. We conclude that l-menthol constitutes a specific stimulant of laryngeal cold receptors and could provide a useful tool for the study of their reflex effects.

The effects of menthol isomers on nasal sensation of airflow.[Pubmed:3370851]

Clin Otolaryngol Allied Sci. 1988 Feb;13(1):25-9.

The effects of inhalation of L-menthol, D-Isomenthol and D-neomenthol, upon nasal resistance and sensation to airflow were investigated in 40 subjects. L-menthol caused a highly significant enhancement of nasal sensation of airflow but despite their great similarity in structure and a similar peppermint smell the isomers D-Isomenthol and D-neomenthol had no effect on nasal sensation of airflow. These findings show that L-menthol has a specific pharmacological action on nasal sensory nerve endings which is not related to its peppermint smell.

Metabolism of Monoterpenes: Conversion of l-Menthone to l-Menthol and d-Neomenthol by Stereospecific Dehydrogenases from Peppermint (Mentha piperita) Leaves.[Pubmed:16662335]

Plant Physiol. 1982 May;69(5):1013-7.

The monoterpene ketone l-menthone is specifically converted to l-menthol and l-menthyl acetate and to d-neomenthol and d-neomenthyl-beta-d-glucoside in mature peppermint (Mentha piperita L. cv. Black Mitcham) leaves. The selectivity of product formation results from compartmentation of the menthol dehydrogenase with the acetyl transferase and that of the neomenthol dehydrogenase with the glucosyl transferase. Soluble enzyme preparations, but not particulate preparations, from mature peppermint leaves catalyzed the NADPH-dependent reduction of l-menthone to both epimeric alcohols, and the two dehydrogenases responsible for these stereospecific transformations were resolved by affinity chromatography on Matrex Gel Red A. Both enzymes have a molecular weight of approximately 35,000, possess a K(m) for NADPH of about 2 x 10(-5)m, are very sensitive to inhibition by thiol-directed reagents, and are not readily reversible. The menthol dehydrogenase showed a pH optimum at 7.5, exhibited a K(m) for l-menthone of about 2.5 x 10(-4)m, and also reduced d-isomenthone to d-neoisomenthol. The neomenthol dehydrogenase showed a pH optimum at 7.6, exhibited a K(m) for l-menthone of about 2.2 x 10(-5)m, and also reduced d-isomenthone to D-Isomenthol. These stereochemically distinct, but otherwise similar, enzymes are of key importance in determining the metabolic fate of menthone in peppermint, and they are probably typical of the class of dehydrogenases thought to be responsible for the metabolism of monoterpene ketones during plant development.