Bridged-bicyclic structures synthesis

Similarly, the mixed homodetic/heterodetic bicyclic structures containing a disulfide bridge are preferably produced as monocyclic compounds that are then typically oxidized in solution adopting standard procedures as described in Section 6.1.1 (Scheme 23, path Bl). If even disulfide formation is performed on resin by the procedures reported in Section 6.1.2, an additional level of selective protection is required for the cysteine thiol functions. The synthetic paths Bl and B2 are also applicable for the synthesis of type II and III bicyclic peptides, independent of whether only lactam bridges are produced or mixtures of lactam/ disulfide bridges. 

Over one hundred compounds have been examined as substrates for HLADH. It has a broad structural specificity and is well suited for organic synthesis. The enzymes reacts with acyclic, mono-, bi-, tri- and tetracyclic (steroidal) substrates. Figure 3 shows a comparison of the substrate specificity of common dehydrogenases. HLADH has a wider use than yeast alcohol or steroid alcohol dehydrogenases. It operates on most substrates with high enantiomeric specificity. Examples in which HLADH exhibits superior selectivity include preparation of stereoisomers of bridged bicyclic... 

Phosphorinane, 4-t-butyl-1 -phenyl-synthesis, 1, 500 Phosphorinane, I-chloro-synthesis, 1, 500 Phosphorinane, 1-hydrocarbyl-I-sulfide synthesis, 1, 500 Phosphorinane, 1-phenyl-synthesis, 1, 499 Phosphorinanes, 1, 497-506 bicyclic bridged derivatives synthesis, 1, 501 conformation, 1, 503-504 NMR, 1, 497 oxidation, 1, 498 reactions, 1, 497 structure, 1, 497, 503-504 sulfuration, 1, 499 synthesis, 1, 499... 

A number of bridged crown ethers have been prepared. Although the Simmons-Park in-out bicyclic amines (see Sect. 1.3.3) are the prototype, Lehn s cryptands (see Chap. 8) are probably better known. Intermediates between the cryptands (which Pedersen referred to as lanterns ) and the simple monoazacrowns are monoazacrowns bridged by a single hydrocarbon strand. Pedersen reports the synthesis of such a structure (see 7, below) which he referred to as a clam compound for the obvious reason . Although Pedersen appears not to have explored the binding properties of his clam in any detail, he did attempt to complex Na and Cs ions. A 0.0001 molar solution of the clam compound is prepared in ethanol. The metal ions Na and Cs are added to the clam-ethanol solutions as salts. Ultraviolet spectra of these solutions indicate that a small amount of the Na is complexed by the clam compound but none of the Cs . 

Bicyclic alkenes. Bicyclic systems like the alkenes 5.188 and 5.189 are well known to be attacked from the exo direction,600 601 on the less hindered convex face of the bicyclic system. Similarly high levels of stereocontrol are found for nucleophilic attack on bicyclic systems, as in the reduction of the ketone 5.190, in which the preference for exo attack overwhelms the steric hindrance offered by the adjacent methyl group.602 Bicyclic systems, especially like these with a zero bridge, are often used in synthesis to give reliably high levels of stereocontrol, with the penalty that there may be many steps needed to open them up to reveal a target structure. 

His synthesis plan is outlined in Figure 7.20. It is a masterpiece of both strategy and tactics and warrants study in some detail. The basic strategy was to build up the tricyclic ring structure from a suitably functionalised bicyclic precursor by trans-annular formation of the final bridging bond. This cyclisation requires the use of a [5.4.0]-bicycloundecane skeleton. These are not readily available and moderately difficult to synthesise. Corey s elegant construction of the required cyclisation substrate therefore adds another admirable dimension to the overall scheme. 

Until recently, the intramolecular cyclization procedure had been used only to synthesize fused heterocyclic structures. The first report of a bridged product, in 1978, involved only a minor amount (9%) of an azabicyclo[3.3.1]nonane derivative obtained from the reaction of cu-carveol with acetonitrile and BF3-Et20. However, several effective examples are now known. These all involve reaction of the nitri-lium intermediate with an internal alkenic nucleophile to yield a 1-azacyclohexene ring and a new carbe-nium ion which undergoes conventional, but stereospecific, Ritter reaction from the least hindered face. Such reactions are typified by formation of the multicyclic structures (64 equation 38) and (65 equation 39), and have considerable potential in the synthesis of complex nitrogen heterocyclic systems since suitable optically pure substrates should undergo completely stereospecific conversions. This has been confirmed by Marschoff in an elegant study on (R)-(+)-limonene (66) and (lS)-(-)-3-pinene (67), which produced opposite enantiomers of the bicyclic amide (68 Scheme 34). 

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