Spiranes

Spinacine — see Imidazo[4,5-c]pyridine-6-carboxylic acid, 4,5,6,7-tetrahydro-Spiniferin-1, ( )-dihydro-occuiTence, 4, 705 synthesis, 4, 670 Spin-spin coupling constants pyridines, 2, 123 Spiramycin antibacterial veterinary use, I, 207 Spirans... 

The property of chirality is determined by overall molecular topology, and there are many molecules that are chiral even though they do not possess an asymmetrically substituted atom. The examples in Scheme 2.2 include allenes (entries 1 and 2) and spiranes (entries 7 and 8). Entries 3 and 4 are examples of separable chiral atropisomers in which the barrier to rotation results from steric restriction of rotation of the bond between the aiyl rings. The chirality of -cyclooctene and Z, -cyclooctadiene is also dependent on restricted rotation. Manipulation of a molecular model will illustrate that each of these molecules can be converted into its enantiomer by a rotational process by which the ring is turned inside-out. ... 

Enamines containing one -hydrogen atom react with the lactone dimer of dimethylketene to form aminocyclohexanediones 116). Polycondensation of acetone diethyl ketal takes place by treating it with morpholine and a catalytic amount of p-toluenesulfonic acid while distilling off the ethanol formed 117-119). The resulting spiran, bicyclo, and cyclooctadienone products differ from the known polycondensation products of acetone, and hence their formation probably involves enamine intermediates 119). 

Cyclization of the two pendant alkyl side chains on barbiturates to form a spiran is consistent with sedative-hypnotic activity. The synthesis of this most complex barbiturate starts by alkylation of ethyl acetoacetate with 2-chloropentan-3-one to give 152. Hydrolysis and decarboxylation under acidic conditions gives the diketone, 153. This intermediate is then reduced to the diol (154), and that is converted to the dibromide (155) by means of hydrogen bromide. Double Internal alkylation of ethyl... 

Research on novel fungal secondary metabolites resulted in the isolation of an interesting spiran, griseofulvin (15), from fermentation beers of the mold Penicillium griseofulvum. 

The second synthesis follows an entirely different synthetic plan—one dependent upon a double-Michael reaction to establish the spiran junction. Chlorophenol, 7, is reacted with chloro-acetylchloride to give coumaranone, 16. This is treated with methoxyethynyl propenyl ketone (17) (itself prepared by 1,2-... 

The anxiolytic agent buspirone (131) is notable for the fact that it does not interact with the receptor for the benzodiazepines. This difference in biochemical pharmacology is reflected in the fact that buspirone (131) seems to be devoid of some of the characteristic benzodiazepine side effects. The spiran function is apparently not required for anxiolytic activity. Alkylation of 3,3-dimethylglutarimide with dichlorobutane in the presence of strong base yields the intermedi-... 

Among other types of compounds that contain the system illustrated in Figure 4.2 and that are similarly chiral if both sides are dissymmetric are spiranes (e.g., 21) and compounds with exocyclic double bonds (e.g., 22). 

Oleandomycin, its ester (triacetyloleandomycin) and spiran rdn have a similar range of activity as erythromycin but are less active. Resistance develops only slowly in chnical practice. However, cross-resistance may occur between all four members of this group. 

Comparison (Tables 7-9) shows that 47 and 48 are similar in their host properties, but they are not equivalent in hehavior. Thus, host compound 48 is more qualified to select according to spatial aspects (see benzene derivatives) and, as a rule, it also forms the thermally more stable inclusions. This may be attributed to the rigid molecular geometry of the spirane 48, whereas the biaryl 47 allows sterical adaptation to different guests via the flexible hinge to a certain degree. 

The synthesis of propellanes and spirans is reviewed, attempting to explain why a starting material sometimes yields a member of one class or the other, but apparently not a mixture of both. 

To emphasize this statement I should like to begin with a heterocyclic case which provides an outlet for the molecule s behavior that leads to neither propellane or spiran albeit, on paper, both of these types might be expected to form. In Mulheim/Ruhr the following reaction was studied ... 

The product 1 is formed exclusively2. No propellane is formed. An explanation has been given by a group interested more in propellanes than in spirans and therefore considered only the relative stability between 1 and 2 3). 

To be quite formal about the connection between spirans and propellanes an interesting pathway may be cited, although admittedly, it is farfetched. 

There are many more syntheses of heterocyclic propellanes from 1,1,2,2-substituted carbocyclic starting materials. The tetrol discussed above, when treated with KHS04 at 170-190 °C affords the dioxa[3.3.2]propellane shown no isomeric spiran is mentioned. Although the yield is only 50% perhaps some dispiran is hiding in the brauner Ruckstand from which the propellane diether is either crystallized at low... 

The work which casts the most light on our subject, is, I think, that of the Conia and the Fitjer groups. It appears from several joint papers that the younger man had worked in the laboratory of the elder, and perhaps thus increased his interest in spirans of great beauty1. 

It should be possible to develop a general route from di-, tri, etc. — spirans of suitable ring size to afford the respective mono-, bis-, tris-, etc. — propellanes. 

The use of carbene additions to MCP derivatives has lately become a general strategy for obtaining spiropentanes and higher spiranic triangulanes. 

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