Drug synthesis synthons

Various bioisosteric replacements for a phenolic hydroxyl have been explored. One such, a lactam NH, is incorporated into the design of the 3-adrenergic blocker, carteolol O)- The fundamental synthon is carbostyril derivative K This is reacted in the usual manner with epichlorohydrin to give which is in turn reacted with t-butylamine to complete the synthesis of carteolol (3 ), a drug that appears to have relatively reduced nonspecific myocardial depressant action. Carrying this de-... 

Figure 13 Synthesis of chiral synthon for anticholesterol drug SQ 33600 stereoselective microbial reduction of 4-chloro-3-oxobutanoic acid methyl ester (39).

Despite their low cost and abundant availability, the applications of monoterpenes as chiral synthons or building blocks for synthesis of chiral fine chemicals on an industrial scale have lagged far behind amino acids and carbohydrates. Most of the work in this area is related to multi-step total synthesis of complex natural products in laboratory scale. With the structures of new drug candidates in the research and development pipeline of pharmaceutical companies getting bigger and more complicated, the application of more sophisticated chiral building blocks such as the terpenes will... 

All the optically active terpenes mentioned in this chapter are commercially available in bulk (>kg) quantities and are fairly inexpensive. Although many of them are isolated from natural sources, they can also be produced economically by synthetic methods. Actually, two thirds of these monoterpenes sold in the market today are manufactured by synthetic or semi-synthetic routes. These optically active molecules usually possess simple carbocyclic rings with one or two stereo-genic centers and have modest functionality for convenient structural manipulations. These unique features render them attractive as chiral pool materials for synthesis of optically active fine chemicals or pharmaceuticals. Industrial applications of these terpenes as chiral auxiliaries, chiral synthons, and chiral reagents have increased significantly in recent years. The expansion of the chiral pool into terpenes will continue with the increase in complexity and chirality of new drug candidates in the research and development pipeline of pharmaceutical companies. 

For other anti-inflammation drugs such as Naproxen59 and Fenoprofen,60 only the S-isomer is biologically active. Since tedious resolutions are necessary to prepare these compounds, it would be desirable to develop a general asymmetric synthesis of the S(+) arylpropionic acids by microbial oxidation of pro-chiral substrates. This concept has been successfully applied in the preparation of a chiral metabolite of 29. Oxidation of one of the enan-tiotopic methyl groups in 30 with sulfurescens furnished the chiral diol 31.61 A similar oxidation of isobutyric acid (32)62 to S-(+)-3-hydroxy-2-mdthylpropionic acid (33) has been recently employed in the synthesis of the a-tocopherol synthon (34).63... 

Benzenesulfonamide, Ar,AT-dibromo-4-methyl-(TsNBr2) bromohydrination with, 287 Benzenesulfonamides reductive cleavage, 247 synthesis of drugs, 301, 307-308 Benzenesulfonic acids. See Sulfonic acids Benzenesulfonic acid, 4-methyl-, esters (tosylates) alkyl a-synthons, 16, 24, 47, 93 fragmentation of, 89 rearrangement of, 32 reductive cleavage of, 114, 202-203 —, 4-methyl-, hydrazide (tosylhydrazine) hydrazones of fragmentation, 89 reduction, 109... 

Although the structures of heterocyclic drugs often look complicated, their synthesis is usually jf the uttermost simplicity. We start with syntheses in which benzylic anions or halides are igain the key synthons. 

The formation of optically active synthons and the ready availability of such materials for synthesis are important because optically pure end-products often will be a prerequisite for incorporation into ethical drug formulations and important agricultural aids in the future. While one of... 

Amidines are of interest as the structural units with wide utility in drug design and as synthons for the synthesis... 

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