Synthesis of A-Ring Fragment

The key step in the synthesis of A-ring fragment 50 [56] is the chelation-controlled addition of allylstannane 53 to aldehyde 52, which sets the C7 stereocenter and introduces the C8 gem-dimethyl moiety. Aldehyde 52 is itself prepared from 1,3-propanediol using the author s protocol for titanium-catalyzed enantioselective allylstannation [57], which sets the C5 stereocenter, followed by chelation-controlled Mukaiyama aldol addition [58] to establish the C3 stereocenter (Scheme 5.6). 

Scheme 5.9 Synthesis of A-ring fragment 68 via C-C bond forming transfer hydrogenation...

An intramolecular Diels-Alder reaction of an alkynyl sulfone was used [537] in the synthesis of a ring fragment of vitamin D3. 

In 2003, Theodorakis et al. described the asymmetric synthesis of a key fragment corresponding to borrelidin (267, Figure 7.7). This macrolide natural product was isolated from Streptomyces rochei in 1949 and exhibits a broad antiviral and antibacterial prolile. Structurally, it contains an atypical 18-membered ring distinguished by a 1,3,5,7-skipped methylene chain, cyclopentane carboxylic acid, and conjugate cyanodiene unit. 

The strain of cycloproparenes is the principal obstacle that must be overcome in their synthesis. Cycloproparenes decompose usually at moderate temperatures, and they undergo ring-opening in the presence of electrophilic or metallic reagents. In contrast, they support even strongly basic conditions quite well. Accordingly, most successful cycloproparene syntheses use some base-induced elimination in the last step. Alternatively, flash vacuum pyrolytic or photochemical extrusion of a neutral fragment, followed by biradical closure or flash vacuum pyrolysis may be used. In these latter approaches the reaction conditions are neutral, and reactive products may be trapped at low temperatures. 

Novel polycyclic heterocyclic systems including the isoxazoline ring were described. Thus, oximes 191 and 193 in the presence of sodium hypochlorite afforded heterocycles 192 or 194, respectively (equations 83 and 84). Intramolecular cycloaddition of nitrile oxide was used in the synthesis of the A-ring fragments of la,25-dihydrovitamin D3 and taxane diterpenoids, sulphur-containing isoxazoles, fluoro-substituted aminocyclopentanols and aminocyclopentitols . New gem- and vic-disubstituted effects in such cyclization reactions have been reviewed by Jung. ... 

The photolysis of cyclic polysilanes results in ring contraction with concomitant extrusion of a silylene fragment. Although the formation of two reactive intermediates potentially complicates mechanisms for product formation, it has provided a useful method for the synthesis of both unstable and stable disilenes... 

Figure 12. Three-dimensional template synthesis of interlocked ring systems induced by a transition metal. The metal center m disposes the two f-f fragments perpendicular to one another. Functions f and g react to form the links.

A similar cyclization is also used in the synthesis of a modified estron with ring A fused to a seven-membered lactone fragment <1999TL1771>. 

We have recently reported the synthesis of a [2]rotaxane constructed around a Ru(diimine)2+ core [95]. The ring was a derivative of dmbp, and, in the course of the threading reaction, we noticed that both exo- and endo-coordination to the ruthenium(II) centre of the rod-like fragment take place, as schematically represented in Fig. 17. 

Synthesis of Cyclic Peptide 14 an Alkyne-bridged Mimic of the Nisin A-Ring Fragment... 

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