Serendipity

One may perhaps wonder why serendipity should be considered under operation of carbon fiber plant but there is a good reason. The word serendipity was coined by Horace Walpole in 1754 and is defined in the dictionary as the faculty of discovering pleasing or valuable things by chance. However, Louis Pasteur said In the fields of observation, chance favours only the prepared mind, later to be paraphrased by an eminent American physicist, Joseph Henry, as The seeds of great discovery are constantly floating around us, but they only take root in minds well prepared to receive them [1]. 

The process of discovery can be divided into finding and the recognition of the finding, the latter probably being the more important and diflfieult phase [2]. 

There is no doubt that curiosity and perception are important parameters and Lenox [3] has described how these characteristics can be encouraged in the student  

Being flexible in thinking and interpreting results, including the unexpected and not dismissing them as incorrect. 

Undertaking careful and intensive study of the field under investigation. 

In chemistry, many important chemical transformations were discovered accidentally. Indeed, serendipity, which emanates from researchers with keen observation, open-mindedness, good instincts, and scientific intuition, has played a key role in science in general. 

Under these conditions, 107 was produced exclusively at the expense of 108. It was proposed that nonpolar solvent (toluene) would disfavor the charged intermediate 110, thus favoring the production of 107. For the very electron-deficient 4-amino-pyrimidine, heating a toluene solution to 100 °C in the presence of TsOH or InCl3 was necessary to ensure the formation of imidazol[l,2-a]heterocycles [60], Using TMSCN as a source of both cyanide and isocyanide equivalent, Hulme and coworkers combined the above reaction with the Strecker reaction under microwave irradiation conditions to provide highly functionalized heterocycles [61]. Other 

There seems to be no major limitation regarding the selection of aldehydes and isonitriles. For 2-aminoazenes, both heteroaromatic amidines and heteroaromatic guanidines participated in this novel 3CR. Flowever, aliphatic amidines were found to be inactive. Many variants have since been reported by different research groups, both academic and industrial, due to the medicinal importance of this family of heterocycles [68]. 

2-Hydroxy-l,4-naphthoquinone, 4-hydroxy-6-methylpyrone, and a-naphthol can be used instead of 116 to afford the corresponding condensation products in good to excellent yields. 

More recently, the same group reported that acetic anhydride can also act as an electrophile to trap the zwitterionic intermediate 109 and developed a three-component synthesis of 2,5-dihydro-5-imino-2-methylfuran-3,4-dicarboxylates [74]. More significantly, they developed an elegant four-component synthesis of 3,4-dihydro-coumarin derivatives by reaction of salicylaldehyde, Meldrum s acid, isocyanide, and 

In this chapter we focused on metrics designed to improve the quality of a compound library. Each metric can be rationalized most can be measured. Serendipity is not necessarily 

One of the celebrated illustrations of serendipity in drug discovery has to be the cis-platin drugs. Turning off the current did not kill the interesting therapeutic effect on tumor cells, and some alert scientists found the reason why. Penicillin, barbiturates, and more recently Viagra definitely underline the case for serendipity as a metric in drug discovery. 

There will be many more fascinating illustrations buried in the scientific literature and masked by rational arguments instead of the story of what actually happened. There has to be almost no chemist in the world who will not acknowledge, perhaps privately, that luck is one of the nicest surprises in synthesis—that there must be room for serendipity. It is just that no one really wants to write about it  

Library metrics lead us to believe that only certain classes of compounds can ever be seriously considered as potentially becoming drugs. Druglikeness, novelty, and diversity can become such awful mantras that we will miss the blue sky quantum leaps into new drug types. Even today, there is still room in the screening programs of some companies for compounds that are quite remote from the metric-designed library. 

Since the blossom oil of lily of the valley is not commercially available, the perfumers have to rely on synthetic substitutes, such as hydroxy-citronellal (1), Lilial (3) and Bourgeonal (6) to create their muguet fragrances. The oldest lily of the valley odorants, hydroxycitronellal and cyclamen aldehyde (2) (Winthrop Chem. Corp., 1929), were discovered by chance. Serendipity still continues to play an important role. Anselmi et al. (1992) synthesized and organoleptically screened a series of 38 tetrahydropyranyl ethers. This class of compounds was chosen because of their ease of synthesis and purification, and because of their stability in alkaline media, conditions under which aldehydes tend to undergo aldol condensations. Two compounds (24 and 25) were described as having a white, floral odour reminiscent of hydroxycitro- 

The following two Case Studies are commonly cited examples of serendipitous drug discoveries. Both show the clear role of observation by the researchers. 

After considerable investigation, a series of events had to occur for Fleming to make his observation. First, Fleming left his Petri dishes on the bench top instead of in an incubator. Second, research on the floor below Fleming s focused on the effect of mold on allergies. 

The source of Fleming s mold, a particularly uncommon strain, was present in the downstairs laboratory. Third, the first days of Fleming s vacation were cold. The cool laboratory allowed the mold to grow and infuse the surrounding culture medium with penicillin. Fourth, the latter vacation days were warm, providing conditions ideal 

CH2CH=CHCH2CH3 2-pentenylpeniciUin CH2Ph benzylpeniciUin (penicillin G) 

The four untreated mice died within 24 hours. One of the treated mice died two days later, and all three other treated mice survived. Based on this success and others, research advanced quickly. By early 1941, penicillin was tested in humans. Until the end of World War II, almost all penicillin produced was used to treat injured Allied soldiers. 

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The lead discovery process is depicted in Figure 10.4-4 and shows how the different methods are interconnected. A lead structure can be discovered by serendipity. In rational drug design all information available about a target serves to direct... 

The three princes of Serendip, Balakrama, Vijayo, and Rajahsigha, as they traveled "...were always making discoveries, by accident and sagacity, of things they were not in quest of..." ... 

If in line with Maher s account, Mendeleev s fellow chemists were very confident about germanium ahead of its actual discovery on account of his previous successes (and we have seen no evidence that they were), then they were right only by serendipity. But there was surely enough clearsightedness—at any rate amongst experts—about the total picture regarding Mendeleev and prediction to make it very doubtful that his fellow chemists would in fact have had the unconstrained confidence attributed to them by Maher. 

The subsequent advance was rather fortuitous and rested more with serendipity than with scientific logic. A search was made for cheaper more effective replacements for casein hydrolysate. Amongst the tested materials was com steep liquor (CSL). CSL is a by-product of the manufacture of starch from maize kemals. Whole maize is incubated in warm water, at 50°C acidified with SO2. Thermophilic bacteria hydrolyse proteins and other components of the kemals, thereby loosening the starch granules. These are removed, leaving behind the steep liquor which is used to treat further maize kemals. Ultimately, the liquor is too viscous to re-use and the liquor is concentrated and used as cattle feed. It was this material that was used for penicillin fermentation. Surprisingly, the yield of penicillin increased by a further 5-10 fold giving yields of 50-100 ig ml. 

Logic, Psychology, and Serendipity of Scientific Discoveries - An Interlude... 

I think it was worthwhile to take a specific case to show that conclusion. Its major purpose is to make Popperian logic and Kuhn s unpredictable circle of normal science, crisis, and revolution better known among chemists and to show how both theories - those of Popper and Kuhn - commingle in the development of scientific discoveries. A third phenomenon should also be mentioned, although it did not play a role in our specific case, namely serendipity, i. e., the gift of making valuable discoveries not sought for. The word serendipity was coined by the British writer Horace Walpole in a letter in 1754 based on the title of the Persian fairy-tale The... 

Sir Bernard Lovell, the founder of Britain s Jodrell Bank Observatory, brings our attention to a present development which, unfortunately, does not favor serendipitous discoveries. What he wrote about astronomy in 1984 is certainly valid for chemistry too I was enthusiastic when. .. computers became a major force in astronomical research. .. But even the greatest blessings tend to be mixed. .. Computers are no exception. .. I fear that literal-minded, narrowly focused computerized research is proving antithetical to the free exercise of that happy faculty known as serendipity. .. . 

Sensitization of ArNJ in spectroscopy 280 f. Serendipity, in scientific discoveries 213,217 ff. Silver halide photography 283 Spherands 294 f. 

This book contains what I call an interlude on the logic, the psychology, and the serendipity of scientific discoveries. Readers may wonder what the correlation is between that short Chapter 9 and diazo chemistry. The specific reason for including it was to elucidate the dediazoniation mechanism of aromatic diazonium ions, but I expanded this mechanistic discussion (Sec. 8.3) in the interlude by including general aspects originating in the philosophy of science as developed by Karl Popper and Thomas S. Kuhn, ideas which, in my opinion, should be better known by all scientists working in chemical research. 

In 1950, Audrey Smith and Christopher Polge in Mill Hill, England, discovered that compounds like glycerol in molar concentrations can reduce or eliminate slow freezing injury in sperm and other cells. The story of how they made the discovery is a nice illustration of serendipity. Although repeatedly failing to preserve the... 

Finally, two more anionic phosphate anions with six oxygen substituents at phosphorus (Fig. 5) were isolated by serendipity. Compound 25 [43] was isolated from the reaction of naphthalene-2,3-diol and phosphonitrilic chloride in... 

One should not lightly dismiss the importance of serendipity in the history of drug discovery. In this context, the tale of the antiallergy drug Intal is particularly interesting [1], The toothpick plant (Ammi visnaga) originates in the... 

Chance (or serendipity as embittered biotech CEOs like to call it) plays a major factor in the successful outcome of an R D program. External forces in the marketplace can make or break small companies hence the environment is highly volatile and subject to change rapidly. 

All this, in summary, would amount to additional sections on conductive polymers and to a future chapter on semiconductive polymers, currently representing an encouraging outlook for a journey begun in serendipity. 

The next milestone in the development of organic synthesis was the preparation of the first synthetic dye, mauveine (aniline purple) by Perkin in 1856 Perkin, 1856, 1862). This is generally regarded as the first industrial organic synthesis. It is also a remarkable example of serendipity. Perkin s goal was the synthesis of the antimalarial drug quinine by oxidation of N-allyl toluidine (Fig. 2.4). 

Design and Serendipity in the Discovery and Development of Homogeneous Catalysts for... 

Initial serendipity and long-term design leads to regioselective alkane functionalization. 

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