Macrocyclic musk

Other commonly occurring chemical groups ia essential oils iaclude aromatics such as P-phenethyl alcohol, eugenol, vanillin, ben2aldehyde, cinnamaldehyde, etc heterocycHcs such as iadole (qv), pyra2iaes, thia2oles, etc hydrocarbons (Liaear, branched, saturated, or unsaturated) oxygenated compounds such as alcohols, acids, aldehydes, ketones, ethers and macrocyclic compounds such as the macrocyclic musks, which can be both saturated and unsaturated. 

In addition to large-scale process work, there is also some effort expended in providing synthetic methods for producing small amounts (<100 kg/yr) of materials needed for replacement of naturals that are being discontinued or in short supply. Examples are ambrinol (59) and dihydro-y-ionone (60) for the replacement of ambergris. More recendy, tincture of tonquin musk has been replaced by using, among other materials, mixtures of macrocyclic ketones and alcohols which have been found in the natural substance. 

Syntheses of macrocyclic musks, among them lactones, dilactones, and oxalac-tones 99S1707. 

The cross-dimerization reaction is very commonly employed for the manufacture of intermediates for synthetic musks, which have become an important class of perfumery chemicals. Synthetic musks have been the target of extensive research over the years due to a conservation order placed on the musk deer. Nitro musks are being steadily replaced by non-nitro polycyclic musks becau.se of technical drawbacks and health aspects of the former, which are explosive, sensitive, and virtually nonbiodegradable. Non-nitro musks, on the other hand exhibit better stability to light and alkali, and more nearly duplicate the odour of the macrocyclic musks occurring in nature. Indian musk odorants are easily soluble in alcohol and perfume compositions. They have the added advantage of non-discoloration in soap and domestic products. In view of the low price, their future in the perfume industry appears very promising. 

Singlet oxygen reacts with electron rich or highly strained alkenes to form 1,2-dioxetanes. These four-membered ring peroxides decompose on warming to two carbonyl compounds (or moieties), usually with appearance of light emission (chemiluminescence). The macrocyclic bis-lactone in (6.17)608>, a musk fragrance, has been synthesized via such a sequence. 

Compounds used in the database were obtained from literature reports of chemical structure and odor quality (7-11). In Table 1, a list of the compounds comprising the database is given. The macrocyclic and nitroaromatic musks are of strong, medium, weak, or unspecified odor intensity the nonmusks are odorless or have an odor other than musk. Information about odor quality and intensity is contained in the activity label associated with each compound. It should be emphasized that a musk compound labeled as weak, medium, or strong refers only to the change in its odor threshold, not to any change in its odor quality. Structural classes present in the dataset are shown in Fig. 1. Natural musks, whose sources include both rare animal and plant species, are... 

Fig. 4. A plot of the two largest principal components of the 312 compounds and the 871 molecular descriptors comprising the training set. 1 = macrocyclic nonmusk, 2 = aromatic nitro nonmusks, 3 = macrocyclic musks, and 4 = aromatic nitro musks. The plane defined by the two largest principal components accounts for 39% of the total cumulative variance.

The smell of musk is important in perfumes and cosmetics, and is obtained from the glands of small animals. There are several types of synthetic musk the aromatic musk is built on dinitrobenzene the steroid musk is built around cholesterol as four staggered fused rings and the macrocyclic musk is built on a 15-member carbon ring. Aside from the ability to elicit a pungent sensation in the nostrils and an emotional response of masculinity, we have not found the common structure responsible for these sensations. 

The classical scent of the sea is afforded by ambergris, which is also the best fixative for perfumes. Once secured from whales, ambergris can now be legally provided by chemical synthesis (Science whaling 2000). Other fixatives are obtained from land animals, such as castoreum, civet, and musk. The first one is a phenolic substance and the latter two macrocyclic ketones that have stimulated the earfy methodologies for the synthesis of macrocyclic conqjoimds... 

Cyclohexadecen-l-one can be added to perfume compositions as a substitute for the natural macrocyclic ketone musks. 

The macrocyclic esters hold a special position among the industrially produced lactone fragrance materials. Like the well-known macrocyclic ketones, they have outstanding odor properties as musks. However, the lactones can be prepared more easily than the ketones, for example, by depolymerization of the corresponding linear polyesters. Since replacement of a methylene unit by oxygen affects the odor of these compounds very little, oxalactones with 15-17-membered rings... 

Muscone and related macrocyclic ketones are responsible for the odor of musk [260,261]. Like other animal secretions, musk was preferentially used as an alcoholic tincture in fine fragrances. FCT 1983 (21) p. 865 [68991-41-3], [90064-09-8]. 

Macrocyclic lactones like ambrettolide (7-hexadecen-l,16-olide) 158, 15-pentadecanolide (cyclopentadecanolide) 159, hexadecanolide (cyclohexa-decanolide) 160 and cyclohexadec-7-enolide 161 (Structure 4.48) are called musks. They are found in a variety of essential oils, e.g. ambrette seed oil and angelica root oil [1-4, 21-23, 62]. 

Musks are important ingredients of fragrance formulations, but almost all the musks used are polycyclic aromatics produced chemically from petrochemi-cally derived raw materials. Naturally occurring musks include the macrocyclic lactones found in some plants, such as ambrette seedoil and galbanum, and the keto musks produced by some animals, such as musk deer and civet cats. 

Scheme 23.18 a De novo biosynthesis of coconut-like 6-pentyl-a-pyrone by Trichoderma sp. b Production of macrocyclic musk-like lactones by a combination of microbial co-hydroxylations and co-l-hydroxylations and subsequent chemical conversion steps, c Production of macrocyclic musk fragrances initiated by terminal oxidation of hydrocarbons with Candida tropicalis... 

Synthetic musks are important ingredients for the fragrance industry. They are heavily used in laundry detergents, fabric softeners, cleaning products, air fresheners, and so on, and in cosmetic and personal hygiene products such as hand soap, shampoo, and perfume. Nitro, polycyclic, macrocyclic, and the newest dass, alicydic musks constitute the four major classes. The OSPAR (Oslo-Paris) Commission summarized information on their environmental behavior that was relevant to its charge, namely protection of the northeast Atlantic marine environment [37]. Most of the identified uses of synthetic musks are expected to lead to their release to... 

Table 20.1 shows the detection thresholds of a number of perfume materials in air and in water. Note the tremendous range (from 0.002 parts per billion for beta-damascenone to 10,000 parts per billion for phenylacetic acid—both taken in water solutions), the large difference between optical isomers of the same substance (e.g., Nootkatone and alpha-damascone), and the large differences in thresholds reported by different investigators (e.g., benzaldehyde and vanillin). In substances with relatively high water solubility such as vanillin and ethyl vanillin, benzaldehyde, phenylethyl alcohol, and phenylacetic acid, the thresholds in water are very much higher than in air. In poorly water-soluble substances such as pinene and the macrocyclic musk cyclopentadecanolid, the reverse is true. The relative thresholds of a substance in different solvents indicate its performance in different application environments. Substances whose thresholds in water solution are much... 

The preputial (musk) gland of the muskrat contains a number of macrocyclic ketones, such as isomers of civetone (cis-9-cycloheptadecenone), the main odourous component of the secretion of the civet. In the muskrat the main macrocyclic component is the cis-5-isomer of civetone (Figure 9). The glands of both animals also contain a number of other macrocyclic compounds and a variety of fatty acids (24,25,26) which could be precursors of macrocyclic ketones and alcohols as proposed by Stevens in 1945... 

The natural musks were always very expensive and their macrocyclic structures presented synthetic challenges which were not conquered, even on laboratory scale, until the pioneering work of Ruzicka in 1926. It was therefore of major importance to the fragrance industry when, in 1888, Baur discovered the nitromusks. He had actually been working on explosives and noticed that the product of t-butylation of trinitrotoluene (TNT) had a pleasant, sweet, musky odour. The compound was named Musk Baur (38), although the alternative name, Musk Toluene , eventually became more common. For a while it was also known as Tonkinol because of the similarity of its odour to that of musk Tonkin. Baur then searched for analogues of this material and... 

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