Camphor, natural product

Many notable examples of the synthesis of complex natural products from optically pure starting materials have been reported (70). One synthesis of considerable interest is that of taxol [33069-62-4] (74), a potent antitumor agent used clinically. The starting material (73) used ia the first total synthesis of taxol is produced ia enantiomericaHy pure form from inexpensive and readily available /-camphor [464-48-2] (72) (73). 

Camphor, Cj HjgO, occurs in the wood of the camphor tree Laurus camphora) as dextro-camphor. This is the ordinary camphor of commerce, known as Japan camphor, whilst the less common laevo-camphor is found in the oil of Matricaria parthenium. Camphor can also be obtained by the oxidation of borneol or isoborneol with nitric acid. Camphor may be prepared from turpentine in numerous ways, and there are many patents existing for its artificial preparation. Artificial camphor, however, does not appear to be able to compete commercially with the natural product. Amongst the methods may be enumerated the following —... 

An enantiospecific synthesis of longifolene was done starting with camphor, a natural product available in enantiomerically pure form (Scheme 13.31) The tricyclic ring was formed in Step C by an intramolecular Mukaiyama reaction. The dimethyl Multistep Syntheses substituents were formed in Step E-l by hydrogenolysis of the cyclopropane ring. 

Camphor is a 10-carbon odoriferous natural product made from the joining of two isoprene units plus the addition of a ketone. Shown here is its chemical structure. Find and circle the two isoprene units. 

NAPHTHALENE. [CAS 91-20-3], Naphdialene C10H8, is a white solid with a strong smell is also called mothballs, moth flakes, white tar, and tar camphor. Naphthalene is a natural component of fossil fuels such as petroleum and coal it is also formed when natural products such as wood or tobacco are burned. 

Typical resolving agents are summarized in Table 4. Typical acidic resolving agents from natural products are malic acid, tartaric acid and its derivative, camphor sulfonic acids derived from camphor. 10-Camphor sulfonic acid is a strong acid and indicates high capability of making salts with weak bases. 

T. Money, Remote Functionalization of Camphor Application to Natural Product Synthesis, in Organic Synthesis Theory and Applications (T. Hudlicky, Ed.), 1996, 3, JAI, Greenwich, CT. 

The rearrangements of carbocations also play a role in the formation of ter-pene natural products. Menthol and camphor are examples of terpenes derived from plant oils. They are constructed using a common building block, as shown in Section 25-8, and undergo a series of rearrangements in the course of construction to generate the most stable carbocation. 

CC>2Me preferably coordinates to the silver metal. Oppolzer s readily removable camphor sultam not only enforces absolute stereocontrol but also enables the underlying reaction cascade (presumably by lowering the pKa of the glycyl a-proton). Pyrrolidine 199 is converted to diol 200 by a 12-step reaction sequence. Since compound 200 corresponds to an advanced intermediate that has been converted to cyanocyline A <87JA1587>, attainment of 200 constitutes an efficient formal synthesis of this natural product. 

Enantiomeric Mannich bases may be obtained either by using optically active starting materials or by optical resolution of racemic derivatives. In the former case, the reactants are mostly provided by natural products, such as components of essential oils (e.g., camphor ), hormones, nucleic acids, employed as substrates, or a-amino acids - mainly used as amine reagents, etc. A list of optically active reactants reported in the literature is summarized in Table 12. 

Halterman and Vollhardt and Paquette and coworkers have prepared bis(annulated cyclopentadienyl)titanium complexes, and have separated (25) and (26) when starting from the chiral natural product camphor. They have shown that... 

Strictly speaking the terpenes are hydrocarbons which are present in, or are obtained by steam distillation from, certain natural products, such as camphor and oil of turpentine certain of the so-called essential or ethereal oils, mostly from conifer or citrus plants, e.g., oil of lemon various plant resins, and India rubber or caoutchouc. They are the mother substances of the individual constituents of the products just mentioned. In general usage the name terpenes includes not only the hydrocarbons but the various derivatives referred to above. 

The hydrocarbons of the various groups which we have just discussed are the true terpenes. On oxidation these yield alcohol and aldehyde or ketone derivatives. The olefine terpenes, only, yield aldehydes that occur as constituents of natural products known as essential oils (p. 840). The derivatives of both groups of cyclic terpenes which are present in essential oils and plant gums and resins are either secondary alcohols or ketones. Among these latter are the camphors of which common camphor is the most important and best known example. In a general sense all of the oxidation products of the cyclic terpenes are termed camphors. 

Natural Camphor.—Camphor is obtained as a natural product from the camphor tree, Laurus camphor a (or Cinnamomum camphor a) ... 

Citral is an example of a very large group of natural products called terpenes. They are responsible for the characteristic odors of plants such as eucalyptus, pine, mint, peppermint, and lemon. The odors of camphor, menthol, lavender, rose, and hundreds of other fragrances are due to terpenes, which have ten carbon atoms with double bonds, and aldehyde, ketone, or alcohol functional groups. (See Fig. 2.)... 

Bee, Ocotea, bitter almond, brown camphor (sold as camphor 1.070), whole camphor and every other oil. Rock-bottom prices and sizes from 1 lb can to 440-lb. drums. Will source anything you wish. This place is in a dead tie with Liberty Natural Products as bee headquartersi ... 

A useful synthesis (ref.ll)of patchouli alcohol, an important fragrant constituent of patchouli oil, from (+)-camphor, that onetime important natural product which was employed as a plasticiser for nitrocellulose (itself a semi-synthetic polymer), was complicated by structural revision of the sesquiterpene alcohol. Dihydrocarvone (14) obtained by saturation of the ring double bond in carvone, a major constituent of oil of spearmint has been employed for two very different sesquiterpenes, the ketone campherenone (15) and the alcohol, occidentalol (16). In the first case an enol acetate was converted to a bicyclic intermediate by earlier established methodology and the route emulated a plausible biogenetic sequence giving racemic campherenone (ref.12) as shown. Any chirality in (14) is apparently lost. 

Trace amounts of complexes 3 and 20 promote the synthesis of optically pure, multiply functionalized, versatile intermediates such as pyrones or lactones from activated, acid-labile siloxydienes with aldehydes. The reagents typically work under mild conditions and therefore promote the survival of valuable functionality in the dienophile, the diene, and cycloadduct [105-107]. As a consequence this procedure is applied in the total synthesis of various natural products, often requiring an intramolecular Diels-Alder approach [106]. Specific interactivity of the chiral precatalyst Eu(hfc)3 (hfc = 3-(heptafluorpropylhydroxymethylene)-D-camphorate with Danishefsky s diene bearing a chiral auxiliary resulted in cycloaddition products of high diastereofacial excess (95 % eq. (8)) [105]. 

These variously substituted camphor derivatives have in turn been used in a number of syntheses of natural products, some of which also involve Wagner-Meerwein rearrangements in their later stages. Examples drawn from the syntheses of (+)-a-santalene (34),(-)-3-santalene (35), (-)-copacamphene (36) and (-)-sativene (37) are given in Schemes 12-14. 

Aldol reactions using chiral auxiliaries are popular as the stereochemical outcome is usually highly predictable and, as such, they provide a reliable method for the incorporation of adjacent stereocenters. The oxazolidinone-based imides 36 and (ent)-36 are the most commonly employed, and these lead to syn aldol products with high levels of stereocontrol [20]. The reaction can be extended to include a variety of a-heteroatom functionality as in 37 (Scheme 9-13) [21]. Numerous examples of the use of these auxiliaries in the synthesis of polypropionate natural products have been reported. Many related auxiliaries are also available and the camphor-based sultam 38 is notable [22]. 

Similarly, if the racemic mixture is composed of basic drugs, use is made of camphor-10-sulfonic acid, a natural product obtainable as an optically pure enantiomer. An example of the type of reactions involved is shown in Figure 4.13, where a pair of enantiomeric alcohols is resolved by reaction with phthalic anhydride and an optically pure base to form a pair of diastereoisomeric salts. Reactions of this type can be tedious to perform and, with the advent of HPLC with chiral stationary phases, are gradually being replaced. 

The understanding of the degradation of natural products such as camphor has been greatly enhanced by understanding the catalytic cycle of the cytochrome P-450 enzyme P-450cam in structural detail.3,4 These enzymes catalyze the addition of 02 to nonactivated hydrocarbons at room temperatures and pressures - a reaction that requires high temperature to proceed in the absence of a catalyst. O-Methyltransferases are central to the secondary metabolic pathway of phenylpropanoid biosynthesis. The structural basis of the diverse substrate specificities of such enzymes has been studied by solving the crystal structures of chalcone O-methyltransferase and isoflavone O-methyltransferase complexed with the reaction products.5 Structures of these and other enzymes are obviously important for the development of biomimetic and thus environmentally more friendly approaches to natural product synthesis. 

Initial studies [26] carried out with enol carbonates A or P-keto esters B afforded ketones D in high yields and selectivities up to 75% ee [27], using ephedrine or a P-amino alcohol derived from camphor. Surprisingly, cinchona alkaloids bearing the required P-amino alcohol moiety were not tested. It was necessary to wait till 2001 and later for publications describing the use cinchona alkaloids in these reactions, either the natural products or some analogues. 

It may not be out of place to mention that ketones are partly or wholly responsible for the odor of many natural products such as camphor, raspberries, coffee, musk, caraway, butter, rue, and jasmine. 

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