Chemical synthesis structures

CHAPTERS STUDIES OF BIOMACROMOLECUIAR STRUCTURES CHEMICAL SYNTHESIS TABLE 8.1 Selected amino protecting groups, Y in Y—HN - R... 

CHAPTERS STUDIES OF BIOMACROMOLECULAR STRUCTURES CHEMICAL SYNTHESIS... 

The chemical synthesis of carbon-containing molecules has been a very important field of scientific work and endeavor for over a centuiy However, the subject is still far aw ay from being fully developed. One of the major reasons for this is the almost unlimited number of organic structures which can exist as discrete compounds. On the other hand there has been a continuing growth in the ability of chemists to construct increasingly complex molecules. 

The most distinctive aspect of the chemistry of acetylene and terminal alkynes is their acidity As a class compounds of the type RC=CH are the most acidic of all hydro carbons The structural reasons for this property as well as the ways m which it is used to advantage m chemical synthesis are important elements of this chapter... 

Structural drawings of carbohydrates of this type are called Haworth formulas, after the British chemist Sir Walter Norman Haworth (St Andrew s University and the University of Birmingham) Early m his career Haworth contributed to the discovery that carbohydrates exist as cyclic hemiacetals rather than m open chain forms Later he col laborated on an efficient synthesis of vitamin C from carbohydrate precursors This was the first chemical synthesis of a vitamin and provided an inexpensive route to its prepa ration on a commercial scale Haworth was a corecipient of the Nobel Prize for chem istry m 1937... 

Early diffraction photographs of such DNA fibers taken by Rosalind Franklin and Maurice Wilkins in London and interpreted by James Watson and Francis Crick in Cambridge revealed two types of DNA structures A-DNA and B-DNA. The B-DNA form is obtained when DNA is fully hydrated as it is in vivo. A-DNA is obtained under dehydrated nonphysiological conditions. Improvements in the methods for the chemical synthesis of DNA have recently made it possible to study crystals of short DNA molecules of any selected sequence. These studies have essentially confirmed the refined fiber diffraction models for A- and B-DNA and in addition have given details of small structural variations for different DNA sequences. Furthermore, a new structural form of DNA, called Z-DNA, has been discovered. 

It is not surprising that multistep synthesis of challenging and complex target molecules is an engine for the discovery of new synthetic principles and novel methodology which may have very broad application. Just as each component of structural complexity can signal a strategy for synthesis, each obstacle to the realization of a chemical synthesis presents an opportunity for scientific discovery. 

Antithetic Analysis. (Synonymous with Retrosynthetic Analysis) A problem-solving technique for transforming the structure of a synthetic target molecule to a sequence of progressively simpler structures along a pathway which ultimately leads to simple or commercially available starting materials for a chemical synthesis. 

Vane and co-workers isolated a new prostaglandin (initially called PGX) from microsomal fraction of stomach. The structure was established by chemical synthesis from PGP2a (Ref. 1). 

Some six hundred structures of naturally occurring carbogenic molecules appe on the pages which follow, together with the name of each compound and references to the original literature of successful chemical synthesis. Thus, Part Three of this book is effectively a key to the literature of chemical synthesis as applied to the complex molecules of nature. The survey does not include oligomeric or polymeric structures, such as peptides, proteins, carbohydrates and polynucleotides, which fall outside the scope of this book because they can be assembled by repetitive procedures. 

A quick scan of the collection of structures in Part Three will confirm the high level of activity and accomplishment which has been associated with the field of chemical synthesis over the past three decades. Upon closer inspection, it becomes apparent that the rate of achievement of successful syntheses has been increasing steadily with time. As of this writing (1988) there are many laboratories in which outstanding work on multistep synthesis of complex molecules is being carried out. One consequence of this intense effort is that the problem of keeping track of the literature of synthesis has become a difficult one for investigators and students. The... 

There are a large number of naturally occurring molecules which have not yet been obtained by chemical synthesis. A convenient source of information on such compounds is The Dictionary of Organic Compounds, Fifth Addition (1982) and Supplements 1-5, published as a multivolume series by Chapman and Hall, New York and London J. Buckingham, Executive Editor. This compendium contains references to syntheses which are not included in this collection, especially those involving simpler target structures. 

The first chemical synthesis of these substances, using a procedure which yields 1-ribofuranosyl derivatives by pyrimidine bases, was described by Hall. By using the mercuric salt of 6-azathymine and tribenzoate of D-ribofuranosyl chloride, he obtained a mixture of two monoribosyl derivatives and a diribosyl derivative. He determined the structure of the 3-substituted derivative by the similarity of spectra and other properties to those of 3-methyl-6-razauracil. The structure of the 1-ribosyl derivative was then determined from the similarity of the spectra with 6-azathymine deoxyriboside obtained enzymatically. 

Considering a median value of 106"1 possible structures in chemical space clearly indicates that the number of possible structures available is far too large for complete coverage by chemical synthesis and biological screening. It has been... 

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