Basic skeleton

The tetracyclines are a group of antibiotics having an identical 4-ring carbocycHc structure as a basic skeleton and differing from each other chemically only by substituent variation. Figure 1 shows the principal tetracycline derivatives now used commercially. 

Because mono and dibenzocrowns were among the first crowns to be synthesized, and because the syntheses of these molecules were relatively straightforward, quite a number of modifications in the basic skeleton have been reported. Some of these modifications have utilized substituted catechols as starting materials and others have involved transformations on the existing crown. 

Purines — These molecules have basic skeletons of purine heterocycles. Adenine and guanine, intrinsic components of nucleic acids, are also ubiquitous molecules. Related molecules are isoguanine, xanthine, and uric acid. 

Figurel.l. Basic skeleton of the colored form in spiroindolinobenzopyran 1.

The coordinatoclathrate principle is intended for host molecules endowed with both a bulky basic skeleton and appended sensor groups. This design of a general structure requires some differentiations. 

Within the limits of this article, we attached importance to keeping the range of the used sensor groups easy to survey and to limiting variation in respect to the bulky basic skeleton to only a few selected structures which are closely connected with the geometric figure shown in Fig. 9, i.e. molecules shaped like scissors or roofs. 

There is no need for much fantasy to see the relation between a roof-shaped (Fig. 12) and a scissor-like basic structure (cf. Fig. 11). Nevertheless, the following point should be noted Scissor-like molecules (cf. 1) provide considerable (inherent) bulkiness merely due to the basic skeleton. On the other hand, as far as roof-shaped molecules are concerned [cf. 26 (Fig. 12) and 27-42], the presence of polar substituents, suitably positioned, preferably at the top ridge of the molecular roof, are also instrumental in developing molecular bulkiness. 

With reference to hosts and a guest, molecular assemblies have to conform to certain circumstances, generally called complementary relationships. They involve both steric and electronic terms. The objects may be achieved by the use of properly chosen sensor groups and by a suitably tailored basic skeleton as exemplified by the present scissor- or roof-shaped host molecules. From the point of view of the introductory thoughts of this chapter (cf. Sect. 3.1), it is a matter of consideration to see how consistent the scissor or the roof simile is in the light of crystal structures. 

Subsequently we demonstrated the generality and effectiveness of this synthetic approach to bicyclic peroxides. Among the basic skeletons that have been prepared, figure the [2.2.1]-, [2.2.2]-, [3.2.2]-, [4.2.1]- and [4.2.2]-bicycloperoxides, whose structures are shown below. 

Number of Carbon Atoms Basic Skeleton Class... 

Although there is versatility in the synthetic methodologies of each individual quinolone antibacterial, two different methods are utilized to synthesize the basic skeleton of l,4-dihydro-4-oxoquinoline-3-carboxylic acid. The first method is based on the Gould-Jacobs reaction [9] using appropriately substituted aniline derivatives and diethyl ethoxymalonate, which results in the formation of the intermediate anilinomethylenemalonate. Further thermal cyclization of this intermediate followed by hydrolysis gives rise to the targeted l,4-dihydro-4-oxoquinoline-3-carboxylic acid, according to Scheme 1. 

Treatment of the ketone (105) with methanolic KOH led to hydrolysis of the acetate group, retro-aldol reaction and aldol cyclization, which eventually afforded a mixture of epimeric alcohols (106) 33). This strategy was used to construct the basic skeletons of various alkaloids, e.g. talatisamine 34), atisine 35) and chasmanine36). 

It is now clear that the basic skeletons of all pectic substances consist essentially of poly-a-D-galacturonic acids the constituent units of which contain the pyranose ring and are linked glycosidically in a configuration through positions 1 and 4.s 6... 

The basic skeleton of this newly developed group of pigments consists of two anel-lated five-membered rings each of which contains a carbonamide moiety in the ring. 

Steroids, compounds with a cyclopenta[a]phenanthrene skeleton (15), include a wide range of natural products such as sterols (e.g., cholesterol), sex hormones, adrenocorticoid hormones, cardiac glycosides and vitamin D [31]. Sterols are steroids having a hydroxyl group at position 3 of the basic skeleton. Steroids can be found both in plants and in animals. 

In organic synthesis design, like in chess, it can also be interesting to outline some medium- or long-term intermediate "target molecules". We can perharps perform disconnections to obtain certain intermediates, whose structure is appropriate in order to apply transforms of special interest. If this transform represents a reaction that affords the basic skeleton of the target molecule, probably we have attained an excellent retrosynthetic scheme. 

Is it a modification that has involved a rearrangement of the basic skeleton ... 

This reaction has recently been applied for the preparation of aza-analogs with the basic skeleton and functional groups of the extremely cytotoxic sesquiterpenes illudin (208) and ptaquiloside (209) [139]. Compounds 212-215 were successfully prepared by heating bicyclopropylidene (1) with the enantiomeri-cally pure nitrones 210,211 (Scheme 47) [138]. Some of these simple aza-analogs have indeed been found to exhibit DNA-cleaving abilities [138b,c]. 

Scheme47. Preparation of aza-analogs 212-215 with the basic skeleton and functional groups of the sesquiterpenes illudin (208) and ptaquiloside (209) [138]...

Currently we know very little about naturally occurring tetrodotoxin analogs or precursors. Chiriquitoxin, isolated along with tetrodotoxin from the Costa Rican frog Atelopus chiriquiensis (21,22), is known to possess the same basic skeleton as tetrodotoxin but differs by an uncharacterized substituent at C-6, as shown in the structure below. It also was shown, based on isolation experiments, that... 

Incorporating partial structures (a) and (b) into the ring and consideration of the isoprene rule leads to the assignment of structure IV as the basic skeleton for compound III. 

The synthesis of the basic skeleton of 1-benzylisoquinoline alkaloids has been reported by Uff et al. 15) starting from isoquinoline and benzyl chloride (Scheme 5). The preparation of Reissert compound iV-benzyl-l-cyano-l,2-di-hydroisoquinoline (4) was performed in a dichloromethane-water two-phase system with potassium cyanide and benzoyl chloride in about 64-69% yield. The deprotonation of 4 with sodium hydride in dimethylformamide solution, the subsequent alkylation with benzyl chloride, and the final alkaline hydrolysis could be performed as a one-pot reaction sequence to supply 1-benzylisoquinoline (25) in an overall yield of 75-84%. 

The Reissert alkylation method was also utilized for synthesizing the basic skeleton of protoberberine alkaloids (Scheme 21). Reaction of 3,4-dihydroiso-quinoline derivatives 149, 150, and 151 with 2-chloromethylbenzoyl chloride and trimethylsilyl cyanide in methylene chloride gave the corresponding 2-chloromethylbenzoyl-l,2,3,4-tetrahydroisoquinaldonitriles (152, 153, and 154,... 

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