Spiro systems

Spiro systems have two rings sharing a single carbon atom, and since this has essentially a tetrahedral array of 

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Spiro systems can be named by normal procedures [13]. For clarity, any anhydro or deoxy prefixes or chalcogen replacement prefixes (e.g. thio) referring to the spiro... 

In the Spiro systems 30, the aromatic orbitals unsymmetrize the carbonyl orbital. Simultaneously, the carbonyl group can perturb the orthogonal aromatic ring. Nitration of the fluorene derivatives (30) bearing a spiro substituent was studied (Fig. 17) [96, 97]. 

Tephrosone 33, a flavonoid belonging to the tephrorin family (vide supra), was found to possess a dihydrobenzofuran framework . Moreover, a metabolite of Penicillium brevicompactum, namely brevione A 34 was found to contain a spiro system . Neomarinone 35, another metabolite from a marine actinomycete, constitutes an intriguing sesquiterpenoid skeleton <00TL2073>. 

If a tether is attached to the C(3) atom of nitronates (214), the reaction gives rise to spiro systems (215). For these systems, generating a linkage containing three atoms between the six-membered ring and the C,C double bond is a case of choice. It necessarily leads to cis -fusion of two five-membered rings. 

With the exception of the parent compounds, where the Michael adducts are isolated, acrylic esters [see, e.g. 6,7,31,105,111 ] and nitriles [6,7], and vinyl ketones [26, 113, 115] generally yield the cyclopropanes (Table 7.6) under the standard Makosza conditions with chloroform. Mesityl oxide produces a trichlorocyclopropy-lpropyne in low yield (10%) [7]. When there is no substituent, other than the electron-withdrawing group at the a-position of the alkene, further reaction occurs with the trichloromethyl anion to produce spiro systems (35-48%) (Scheme 7.12) [7, 31]. Under analogous conditions, similar spiro systems are formed with a,p-unsaturated steroidal ketones [39]. Generally, bromoform produces cyclo adducts with all alkenes. Vinyl sulphones are converted into the dichlorocyclopropane derivatives either directly or via the base-catalysed cyclization of intermediate trichloromethyl deriva-... 

Apparently, the driving force for the ring opening is the relief of the strain in the spiro system and the formation of the stable carbonate double bond. The double ring opening is probably a concerted process from the initial radical addition product to the open-chain radical. Even though the spiro compound XI is an allyl monomer, it does copolymerize with a wide variety of comonomers. 

The non-detachable prefixes bicyclo-, tricyclo-, etc. and spiro- characterise the bridged and the spiro systems. Numbers in square brackets give necessary information about the lengths and positions of the bridges in these polycyclic systems. 

The intramolecular cycloadditions of cyclic nitronates have received much more attention. The cyclic nitronate structure provides three basic modes of intramolecular cycloaddition (Fig. 2.15). Attachment of the tether to the C(3) position of the nitronate results in the formation of a spiro system (spiro mode). However, if the tether is appended to the C(4) position of the nitronate, the dipolar cycloaddition yields a fused ring system (fused mode). Finally, if the tether is attached at any other point of the cyclic nitronate, the cycloadducts obtained will consist of bicyclic structures (bridged mode). 

Dipole-moment measurements (in benzene) and low-temperature NMR studies (CDCI3-CFCI3 or CDC13-CC14 at -72 to -79°C) gave AG° values for other spiro systems. The AG° values shown in Table XIV are from the NMR measurements,199,200 Buttressing and inductive effects are probably responsible for variations in AG° values. The l-fert-butylpiperidine-4-spiro-2 -oxiran and -2 -thiiran adopt equilibria favoring the axial heteroatom con-formers (dipole-moment measurements) (Table XIV).201... 

Several groups have prepared cyclopentane systems by intramolecular Michael addition.72 Reaction of the triester (292 Scheme 37) with phenyl vinyl ketone (293) and base produces the cyclopentane (295) in good yield via an intermolecular (giving 294) and subsequent intramolecular Michael addition.72 When the Michael acceptor is a cyclohexenone (Scheme 38), the c/s-fused hydrindanone is produced (298 or 297).72b 72f Spiro systems can also be formed by these reactions (300a,b equation 66) in which the Michael addition gives a spiro ring fusion. 

The cyclopropane ring can also be cleaved by a retro-Michael reaction. By appropriate positioning of the carbonyl groups by means of an intramolecular cyclopropanation, controlled ring opening to spiro systems (62),84 bicyclo[3.2.1]octanes (63)82 or bicyclo[2.2.2]octanes (64),82 has been achieved (equations 28-30). 

Among the various strategies available for p-tum mimics, the Freidinger y-lactam structure (1), or a spiro system [144] (2),has been found suitable for the design of a variety of medicinally relevant targets. In addition, it has been recently reported that use of a,a-disubstituted [S-lactam (3) could also be a good approach to promote a p-tum folding in a peptide chain [145] (Fig. 12). 

The tricyclic spiro system having one methyl group was also examined (Fig. 6) (24, 25). This system can give the four isomers 23, 24, 26, and 27. The isomers 23 and 24 come from the cyclization of dihydroxyketone 22 whereas the isomers 26 and 27 come from the cyclization of the isomeric dihydroxyketone 25. In this case, 22 and 25 are not interconvertible under acidic conditions. Each spiro isomer can exist in two different conformations. The theoretical analysis, however, predicted that isomer 23 exists as a mixture of conformers 23A (0.5 kcal/mol) and 23B (0 kcal/mol) whereas isomer 24 exists in the conformation 24A (0 kcal/mol) (Fig. 6). Approximately, a 1 1 mixture of isomers 23 and 24 should therefore be isolated from the cyclization of dihydroxyketone 22. 

The methyl substituted spiro system JO (Fig. 3) was also studied (24, 25). With this system, two isomers JJ and J2 are possible and molecular models show that they can each exist in four different conformations. Evaluation of the anomeric and the steric effects of each conformation leads to the prediction that isomer JJ exists in the conformation 11A only (0 kcal/mol relative to the other conformations) whereas isomer 12 is a mixture of a major (12A, 2.4 kcal/mol) and a minor (12B, 2.9 kcal/mol) conformer. However, since isomers JJ and J2 are interconvertible (JJ can be converted into the mirror image of J2 by opening and reclosure of the acetal function) and... 

In the cyclocondensation, in the second diamine group of 1,2-diamine both the ortho and ipso heterocycle atoms may react. Such a nontrivial result was obtained while studying the interaction of chalcones 157 and cyclic unsaturated ketones 161 with 5,6-diamino- 1,3-dimethyluracil 55 [61, 62]. This refuted the data [57] on the oxazepine 158 structure of the products of this reaction the formation of the spiro systems 159 and 162 was unambiguously proven... 

Both malonyl-CoA and methylmalonyl-CoA are then utilized as extender units. The heterocyclic rings are easily accounted for the spiro system is merely a ketal, though the tetrahydrofu-ran ring requires further hydroxylations of the basic skeleton for its construction. Avermectins are usually isolated as a mixture in which the main a component has a 2-methylpropyl group... 

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