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The increasing emergence of multi-drug-resistant microorganisms has led the World Health Organisation to plead for action to be taken against antimicrobial resistance. The fungal secondary metabolite (+)-pleuromutilin displays antibacterial activity with a novel mode of action: pleuromutilin derivatives bind to functionally important nucleotides within the peptidyl transfer centre of the prokaryotic ribosome and inhibit bacterial protein synthesis. The first non-racemic total synthesis of the antibiotic natural product pleuromutilin has been developed. A chiral pool strategy has been employed to gain access to the cyclisation substrate, which underwent a SmI2-mediated cyclisation cascade to give the 5,6,8 tricyclic core in a single step. The reaction proceeded with excellent diastereocontrol at the four contiguous stereocentres generated during the cascade. Elaboration of the cyclisation product to (+)-pleuromutilin was achieved by electron transfer reduction of the hindered ester at C5, stereoselective introduction of the hydroxyl at C11 and installation of the quaternary stereocentre at C12. Finally the first efficient conversion of (+)-mutilin to the target was developed. This strategy is now being used for the synthesis of simplified novel analogues of pleuromutilin: access to a range of simplified cores has been demonstrated in 5 steps.

Tremendous synthetic advances in the fields of organic and polymer chemistry have created new opportunities to design advanced, new polymeric materials. Empowered with a suite of advanced synthetic tools, researchers have looked to nature for new inspiration in materials design. Nature has provided a near endless stream of ideas to draw upon for new advanced materials. The goal of this dissertation is to use lessons learned from nature to create cutting-edge, advanced polymeric materials that rely on dynamic molecular interactions. The thesis begins, in Chapter 1, with the background of each individual chapter, including both a guiding principle from nature, as well as, examples of selected previously published work in the field.In Chapter 2, I draw on lessons learned from the human bone to incorporate sacrificial hydrogen bonds into a covalently crosslinked self-healing material. This work addresses the long-standing challenge in the field of self-healing materials by combining robust mechanical and efficient self-healing properties. Specifically, the toughness of the material is increased 7-fold.In Chapter 3, I draw from the observation that nature displays remarkable ranges in mechanical properties from simple building blocks to create a widely tunable metallopolymer system. Specifically, the mechanical performance of the system is tuned from viscous oils to stiff plastics by careful selection of type and amount of added metal. This behavior is explained via ligand exchange mechanism, where associative and dissociative mechanisms are leveraged to achieve widely different properties.In Chapter 4, I imitate the mechanical gradients commonly observed in nature that protect biological materials from damage. Through a sophisticated understanding of metal-ligand crosslinks, I develop a novel approach to generating stiffness gradients in polymeric materials. The result is a mechanical gradient that spans over a 200-fold difference in stiffness.In Chapter 5, I attempt to duplicate the impressive moldability of silicate glass in covalently crosslinked polymer networks. Towards this goal, I have identified the silyl ether motif as a potential key to creating commercially-relevant vitrimer materials. If successful, these vitrimeric materials could replace thermosets in a variety of applications.

Despite the fact that the Times was an afternoon paper and the Courant a morning paper, the two were more alike than they were different throughout the 1950s and 1960s. Each newspaper was increasingly influenced by persons not native to New England, but both retained executives with New England roots. They were closely balanced in manpower, they competed vigorously for the same kinds of news, and (after September, 1968) they presented similar Sunday packages. Carl Lindstrom's charge that newspapers were increasingly dominated by the business offices could hardly be applied fairly to either newspaper in Hartford by 1970. The publishers of both newspapers--and the top two executives of Gannett--were news oriented; that is, they had been newsmen before they became managers. Both newspapers had the benefit of some of the nation's leading editorial thinkers. With so many similarities, it becomes relatively easy to isolate the major ways in which the Courant and the Times differed: (1) The morning Courant had only one direct competitor in its prime circulation territory, whereas the evening Times had nine; (2) the Courant was first and most aggressive -in its drive for circulation in the suburbs and beyond; (3) the Sunday Courant already had become a habit with many readers long before the Times had a Sunday paper, and (4) top-level operations at the Courant followed a consistent pattern through orderly executive succession during a period when the Times was frustrated by internal conflict. (From 1948 to 1970, the Courant had one new publisher, the Times three.) The failure to start a Sunday newspaper in the 1950s, when 52 the Times was still far ahead in daily circulation, may have severely handicapped the Sunday paper that was begun in 1968. It would be rash, however, to write off the 1968 venture as a failure after only one year's performance. Any assessment of the situation must take into account Gannett's ample resources in both money and talent, which still might be sufficient to overcome the effects of the questionable strategy of the 1950s. No prognosis should be attempted on the basis of only one year's circulation and advertising.