Ring systems stereochemistry

Fink, T. and Reymond, J.-L. (2007) Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery. Journal of Chemical Information and Computer Sciences, 47, 342-353. 

A second option is to displace all atoms in Cartesian coordinates and then run an optimization. This second option works well for ring systems, but is not so efficient for long chains. This may also result in changing the stereochemistry of the molecule. 

The reaction of the allylic acetate with a diene system 784 affords the poly-fused ring system 785 by three repeated alkene insertions[487]. An even more strained molecule of the [5.5.5.5] fenestrane 788 has been constructed by a one-pot reaction in a satisfactory yield by the Pd-catalyzed carbonylation-cycliza-tion of 786 without undergoing elimination of /3-hydrogen in the cr-alkylpalla-dium intermediate 787 owing to unfavorable stereochemistry for syn elimination[488]. 

Cholesterol was isolated m the eighteenth century but its structure is so complex that Its correct constitution was not determined until 1932 and its stereochemistry not verified until 1955 Steroids are characterized by the tetracyclic ring system shown m Figure 26 9a As shown m Figure 26 9b cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C 3 a double bond at C 5 methyl groups at C 10 and C 13 and a C Hn side chain at C 17 Isoprene units may be discerned m var lous portions of the cholesterol molecule but the overall correspondence with the iso prene rule is far from perfect Indeed cholesterol has only 27 carbon atoms three too few for It to be classed as a tnterpene... 

Subsequently, other structural variations were reported encompassing compounds such as PS-5 (5) (5), carpetimycin A (6) (6), asparenomycin A (7) (7), and pluracidomycin A (8) (8), from a wide variety of streptomycete strains. Following these stmctures the simplest member of the series, having the completely unsubstituted nucleus, (1, X = CH2), was isolated from bacterial strains of Serratia and Ervinia (9). AH other natural products reported have substituents at both the C-6 and C-2 positions of the bicycHc ring system. Differences in the nature and stereochemistry of these substituents has provided a wide variety of stmctures, and over forty variations have been reported and comprehensively Hsted (10). 

Another system in which the factors constrolling the direction of reagent approach has been studied systematically is the bicyclo[2.2.1]heptane ring system. The stereochemistry of a number of reactions of the parent system and the 7,7-dimethyl derivative have been examined.Some of the results are given in Table 3.13. These reactions reveal... 

Since the stereochemical course of a catalytic hydrogenation is dependent on several factors, " an understanding of the mechanism of the reaction can help in the selection of optimal reaction conditions more reliably than mere copying of a published recipe . In the first section the factors which can influence the product stereochemistry will be discussed from a mechanistic viewpoint. In subsequent sections the hydrogenation of various functional groups in the steroid ring system will be considered. In these sections both mechanistic and empirical correlations will be utilized with the primary emphasis being placed on selective and stereospecific reactions. 

The same qualitative results based on steric and electronic properties of the steroid ring system are found regardless of the structure of the peracid. Thus, although the generality of stereochemistry can be discussed with regard to all peracids, a quantitative comparison is valuable in some instances. 

The stereochemistry of the product resulting from the reaction of a 17-keto steroid with ethylidenetriphenylphosphorane is different from that of the 17-ethylidene steroids obtained by dehydration of 17a-ethyl-17/ -hydroxy compounds, Wolff-Kishner reduction of A -20-keto steroids or by sodium-alcohol or sodium-ammonia " reductions of 17-ethynyl carbinols. These latter products have generally been assumed to possess the trans configuration (C-21 methyl away from the bulk of the ring system) because of anticipated greater stability. The cis configuration for... 

In a study of the stereochemistry of the B-homosteroid ring system, Kohout, Fajkos and Sorm prepared 3 -hydroxy-B-homo-5a-cholestan-7-one acetate... 

Consecutive Michael additions and alkylations can also be used for the diastereoselective synthesis of 5- and 6-membered ring systems. For instance when 6-iodo-2-hexenoates or 7-iodo-2-heptenoates are employed the enolate of the Michael adduct is stereoselectively quenched in situ to provide the cyclic compound with trans stereochemistry (>94 6 diastereomeric ratio). As the enolate geometry of the Michael donor can be controlled, high stereoselectivity can also be reached towards either the syn or anti configuration at the exocyclic... 

Roseophilin (273), a deeply red-colored pentacyclic compound isolated from the culture broth of Streptomyces griseoviridis, is a novel antitumor antibiotic. Compound 273 possesses a topologically unique pentacyclic skeleton, consisting of a 13-membered macrocycle incorporated in an ansa-bridged azafulvene, which in turn is linked to a conjugated heterocyclic ring system. The absolute stereochemistry of roseophilin, as depicted in Fig. 9, was unknown until the first total synthesis published by Tius and Harrington in 2001 [125]. All syn-... 

The synthesis in Scheme 13.13 leads diastereospecifically to the erythro stereoisomer. An intramolecular enolate alkylation in Step B gave a bicyclic intermediate. The relative configuration of C(4) and C(7) was established by the hydrogenation in Step C. The hydrogen is added from the less hindered exo face of the bicyclic enone. This reaction is an example of the use of geometric constraints of a ring system to control relative stereochemistry. 

The Tc02Tc ring system is readily detected in the IR spectrum by the presence of a strong asymmetric stretching mode at 710-700 cm-1 and a weaker symmetric mode at 515 — 450 cm-1. These assignments have been confirmed by 180 labelling. All known dimers have the syn stereochemistry in Fig. 6 and show two v(TcN) absorptions as a result of the in-phase (A in C2v symmetry) and out-of-... 

In a ring system, the resulting alcohol may be axial or equatorial, and much work has gone into examining the stereochemistry of the hydrogenation of sub-... 

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