Key compounds

The key compound m the synthesis of aspirin salicylic acid is prepared from phe nol by a process discovered m the nineteenth century by the German chemist Hermann Kolbe In the Kolbe synthesis also known as the Kolbe—Schmitt reaction, sodium phen oxide IS heated with carbon dioxide under pressure and the reaction mixture is subse quently acidified to yield salicylic acid... 

Vitamin D3 is a key compound m the process by which Ca " is absorbed from the mtes tine Low levels of vitamin D3 lead to Ca " concentrations m the body that are msuffi cient to support proper bone growth resulting m the bone disease called rickets... 

As important as nucleotides of adenosine are to bioenergetics that is not the only indispensable part they play m biology The remainder of this chapter describes how these and related nucleotides are the key compounds m storing and expressing genetic information... 

Adenosine triphosphate (ATP) is a key compound m biological energy storage and delivery... 

Urea and malonic acid give barbituric acid (7), a key compound in medicinal chemistry (see also Hypnotics, SEDATIVES, AND anticonvulsants) ... 

As early as 1967, IFF chemists (11), in an in-depth study of jasmin absolute, identified an ultratrace amount of one of the key compounds in the entire fragrance repoitoire, hydroxycitroneUal [107-75-7] (21). This chemical has been used for many years in almost every "white flower" fragrance to give a very diffusive and lasting lily-of-the-valley and jasmin note, but this represents the only known identification of the compound in nature. This illustrates that the human nose can often predict the presence of a molecule well before the instmmentation becomes sufficiently sensitive to detect it. 

Anthraquinone dyes are derived from several key compounds called dye intermediates, and the methods for preparing these key intermediates can be divided into two types (/) introduction of substituent(s) onto the anthraquinone nucleus, and (2) synthesis of an anthraquinone nucleus having the desired substituents, starting from benzene or naphthalene derivatives (nucleus synthesis). The principal reactions ate nitration and sulfonation, which are very important ia preparing a-substituted anthraquiaones by electrophilic substitution. Nucleus synthesis is important for the production of P-substituted anthraquiaones such as 2-methylanthraquiQone and 2-chloroanthraquiaone. Friedel-Crafts acylation usiag aluminum chloride is appHed for this purpose. Synthesis of quinizatia (1,4-dihydroxyanthraquiQone) is also important. 

Anthraquinone dyes are derived from several key compounds, ie, dye intermediates. Production of these dye intermediates often requires sophisticated production processes and a large amount of investment in plant constmction. The competitiveness of final products, dyestuffs, depends on that of the intermediates, ie, quaUty, cost, and availabiUty. 

Another route presented in the work cited above also finally furnished 16 and 17, although in this case, the intermediate 62, prepared in three steps from indigo (63) via the 0-acetates 64 and 65, served as the precursor leading to the key compound 61 (Scheme 10) [97H(45)1647]. Details of the synthesis of 64 had been given previously by Bergman (82CS193). 

FIGURE 1.7 Key compounds synthesized to eliminate the efficacy (burgundy red) and enhance the affinity (green) of histamine for histamine H2 receptors to make cimetidine, one of the first histamine H2 antagonists of use in the treatment of peptic ulcers. Quotation from James Black [10]. 

Further utility of the Andersen sulphoxides synthesis is demonstrated by the preparation of optically active unsaturated sulphoxides which were first prepared by Stirling and coworkers359 from sulphinate 276 and the appropriate vinylic Grignard reagents. Later on, Posner and Tang360 prepared in a similar way a series of ( )-l-alkenyl p-tolyl sulphoxides. Posner s group accomplished also the synthesis of (+)-(S)-2-(p-tolylsulphinyl)-2-cyclopentenone 287, which is a key compound in the chiral synthesis of various natural products361 (equation 159). 

Cyclization of 148 with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and a subsequent elimination reaction with acetic anhydride and pyridine furnished compound 149. °- Compound 149 was found to be an important key compound for the following synthesis of carba-sugars of the a-L-altro, fi-D-gluco, P-h-allo, and a-D manno modifications. 

These peroxidations affect the aldehydic hydrogen atom, but also hydrocarbon positions in position a of the ketonic carbonyl as already seen (see alcohol group on p.253). Butanone is one of the key compounds that are involved in accidents of this type. The peroxidation is slow, but it seems that when other compounds that can also be moderately peroxidised are present the process is aggravated by their combination. We have already seen an example of such an interaction between 2-butanol and 2-butanone. 

The first non-peptide oxytocin antagonists, based on a spiropiperidine template, were described by Merck in 1992 [68-70]. The binding affinity data for key compounds from this series are summarised in Table 7.2. The initial screening hit, L-342,643, (23), had modest (4/iM) affinity for rat uterine oxytocin receptors and very little vasopressin selectivity [71]. A structure activity relationship (SAR) study was carried out around this template, focussing on the toluenesulphonamide group. This work led to the identification of bulky lipophilic substitution as key to improved oxytocin potency, while the introduction of a carboxylic acid group led to improved... 

Work on this series of non-peptide oxytocin antagonists was then terminated at Merck, in favour of a promising new template. Binding affinity data for key compounds in this new series are summarised in Table 7.3. Some years ago, dihydroquinolinones such as OPC-21268, (28), had been disclosed as vasopressin Vi antagonists. This compound underwent clinical evaluation by Otsuka for hypertension and cardiac failure [76], but was... 

The balance of the compounds in Table VIII support the earlier statement that any compound containing fluorine is toxic to moths. These fluorinated hydrocarbons, phenols, acids, sulfonic acids, and sulfones probably act against moths as stomach poisons. The fluorosulfonic acid derivatives and the sulfone with a fluorinated substituent were key compounds whose toxicity to moths laid the groundwork for the deductions which led to the synthesis and testing of DDT as an insecticide. 

A different iterative method for the construction of ribbon and belt type molecules using tetrafunctionalized arenes and cyclophane monomers was developed by us [42]. The newly designed key compound 23 allows a repeated elongation of a ribbon type molecule by two benzene units (Fig. 12) [43]. 

Reductive dehalogenation cannot be completely controlled, and mostly complicated mixtures were formed which are difficult to separate. Salt elimination opens the possibility of a reaction aimed at polysilane formation. Some examples are shown in Fig. 2. The key compounds are the alkali metal cyclosilanes, which we have isolated via the mercury compounds by the action of sodium/potassium alloy and used for the first time [13]. 

Pyrite is not only one of the key compounds in Wachtershauser s theory, but could also have fulfilled an important function for phosphate chemistry in prebiotic syntheses. A group in Rio de Janeiro studied the conditions for phosphate sorption and desorption under conditions which may have been present in the primeval ocean. In particular, the question arises as to the enrichment of free, soluble inorganic phosphate (Pi), which was probably present in low concentrations similar to those of today (10 7-10 8M) (Miller and Keffe, 1995). Experiments show that acid conditions favour sorption at FeS2, while a weakly alkaline milieu works in an opposite manner. Sorption of Pi can be favoured by various factors, such as hydrophobic coating of pyrite with molecules such as acetate, which could have been formed in the vicinity of hydrothermal systems, or the neutralisation of mineral surface charges by Na+ and K+. 

Oxygenates and olefins are key compound classes in Fischer-Tropsch refining. 

Plants of the genus Allium, e.g. garlic Allium sativum), leek Allium amp-eloprasum), and onion Allium cepa), produce a bewildering variety of sulfur compounds. Selenium analogs for some of these have also been found (Section 11.1.3.6). Much work has focused on garlic (contains more than 100 such materials) and onion.56,66,67 Key compounds for formation of the Allium sulfur-containing secondary metabolites are sulfoxides of cysteine derivatives,... 

The tricyclic compound (441) is a key compound in the synthesis of enan-tiomerically pure indolizidine (442). It was obtained in an intramolecular 1,3-cycloaddition of nitrone (440), by retro-cycloaddition from isoxazolidine (439) (Scheme 2.215) (708). 

The total synthesis of optically active loganin (53) was accomplished by Partridge 25), who photolyzed a solution of the chiral acetate (60) and the ester (56). The intermediate (61) rearranged to the chiral hemiacetal (62), which served as a key compound in the synthesis of chiral loganin (53)15). 

The past 3 years have seen tremendous advances in both the design of Cat K inhibitors and in our understanding of the effect of Cat K inhibition on bone remodeling. The structural diversity of Cat K inhibitors has expanded considerably from simple peptidomimetics to non-peptidic derivatives and even non-covalent inhibitors. The potency, selectivity and pharmacokinetic properties of key compounds are very attractive and seem well-suited to further development. The disclosure of clinical validation of the effect of Cat K inhibition on bone mineral density, plus the provocative data suggesting a decoupling of bone resorption and bone formation provides a compelling framework for further development of Cat K inhibitors for the treatment of osteoporosis. 

---