This dissertation comprises two major components that sequentially describe literature reviews pertinent to tetrahydropyran-containing small macrolides of cyanobacterial origins and research in the field of synthetic organic chemistry that demonstrates synthetic methodology development directed for stereoselective production of highly functionalized oxacycles and their applications in complex molecule synthesis. The research discussion commences with a systematic study towards the total synthesis of (+)-acutiphycin, a highly cytotoxic macrolide with an unknown mode of action. Our convergent route was highlighted by an extensive utilization of the vinylogous Mukaiyama aldol reactions for the construction of both southern and northern hemispheres of the macrolide. The acutiphycin study concluded with a thorough investigation of aldol-mediated advanced fragments coupling strategy. Our research continues with the development of electrophile-induced ether transfer reaction. This novel synthetic method readily generated 1,3-syn diol monoether, a common functionality in polyketide that presents a significant synthetic challenge. This transformation was accomplished by simply exposing homoallylic alkoxymethyl ether to iodine monochloride. The reaction mechanism was proposed via an intermediacy of chloromethyl ether as observed by in situ NMR experiments. The ability to quench the chloromethyl ether intermediate with various nucleophiles, such as cyanide or thiophenol, showcased the versatility of the ether transfer reaction. This strategy readily yielded precursors for the production of six-membered oxygen heterocycles via a general three-step sequence: ether transfer, cyclization, and functionalization reactions. Depending upon the functionalization step, a robust production of stereocomplementary 4-alkoxy-2,6-cis- and trans-disubstituted tetrahydropyrans and trans-2,6-disubstituted-3,4-dihydropyrans was successfully achieved in a stereoselective fashion. These methods were then successfully applied to an efficient construction of the oxacycle core of phorboxazole A and swinholide A. Our final research project describes a concise enantioselective total synthesis of neopeltolide macrolactone. The successful synthetic approach was highlighted by sequential utilization of the ether transfer methodology, functionalization, and radical cyclization to directly install the requisite stereochemistry embedded within neopeltolide's tetrahydropyran ring. Our synthesis only required 14 steps in the longest linear sequence, 15 steps overall. More importantly, it was free of discreet installation steps for protecting groups, thus representing a rare example in complex polyketide synthesis.