Biological synthesis scheme

First, the above-mentioned sensors have major drawbacks, as the detection and recognition event is a function of the nature and characteristics of the side chains, and the side chain functionalization of the CP requires advanced synthesis and extensive purification of numerous monomeric and polymeric derivatives. Second, this generation of sensors primarily employed optical absorption as the source for detection, resulting in lower sensitivity when compared with other sensing systems for biological processes. However, the use of fluorescence detection within these sensing systems could justify continued development. More recent examples include a fluorescent polythiophene derivative with carbohydrate functionalized side chains for the detection of different bacteria [15] and novel synthesis schemes for ligand-functionalization of polythiophenes [16]. 

After assuming a certain mechanism for an observed biological activity—e.g. inhibition of cholinesterase and insecticidal activity—it was interesting to look for deviations. Such deviations could point to new mechanisms and hence a new synthesis scheme. 

The Fuchs group has also prepared [15] dihydrocephalostatin 1 . In this synthesis (Scheme 9), the angular methyl group of keto alcohol 20 (obtained from hecogenin acetate) was functionalized by Meystre s hypoiodite method and oxidized to yield 21. Further reactions via intermediates 22 and 23 afforded 24, which was coupled with a-amino oxime ether 25 (prepared from 18) to give dihydrocephalostatin 1 after deprotection. This dihydro derivative had biological activity comparable to cephalostatin 1. 

This procedure has been expanded to the synthesis of 4-azafluorenone (5H-indeno[l,2-fc]pyridine-5-one) alkaloids, which have significant biological activity (Scheme 4.9). An aldehyde, 1,3-indanedione, aryl ketone, and ammonium acetate are used as reagents. Heating at 120 °C for 6-15 min in a sealed tube and using DMF as solvent proved optimal. 

Many biologically active derivatives are based on the dihydrobenzodiazepine structure. The tranquilizer medazepam is of this type its synthesis (Scheme 9.56) is of interest because of its close resemblance to the Bischler-Napieralski isoquinoline synthesis, in that an amide is subjected to cyclodehydration with PPA. Here, a second nitrogen atom must be present in the side chain, as in the starting amide 9.114. This product is the tranquilizer medazepam (9.115). 

Polyolefin cyclizations have been of substantial value in the synthesis of polycyclic natural products of the terpene type. To a large extent, these syntheses probably resemble the processes by which polycyclic compounds are assembled in nature from linear polyolefins. The most dramatic example of biological synthesis of a polycyclic skeleton from an acyclic intermediate is the conversion of squalene oxide to the steroid lanosterol and then to other steroids. Scheme 8.12 gives some... 

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