Decytospolides A and B are natural products isolated from Cytospora sp. No ZW02 that show mild anticancer properties. The interest in synthesizing these compound lies not in their activities, but rather the simplicity of the structure which could easily be modified to provide more potent derivatives. Previous syntheses of these compounds relied on transition metals to install the tetrahydropyran core or extensive use of protecting groups. Our first generation synthesis made use of the Achmatowicz rearrangement to synthesize the tetrahydropyran moiety. Based on this, a concise, protecting group free synthesis has been accomplished utilizing the Achmatowicz rearrangement of an optically active furanyl alcohol followed by diastereoselective Kishi reduction of the resulting dihydropyranone hemiacetal. <br><br>Carambolaflavone A is a natural product isolated from A. carambola with antidiabetic properties. Notably, these compound promote both insulin secretion and glucose uptake by muscle cells in hyperglycemic rats. A previous synthesis has been reported by Wang and coworkers, however this synthesis does not offer much potential for the formation of derivatives and relies on a C-glycosylation that requires heating for regio- and diastereoselectivity. Progress towards a concise synthesis has been made featuring a Lewis acid promoted highly diastereoselective substrate controlled C-glycosylation that does not require heating and a one pot oxidation of chroman to chromone utilizing DDQ. Further research is underway to complete the synthesis of this molecule by an oxidative addition to the chromone and subsequent removal of protecting groups.

HIV-1 protease inhibitor drugs are important components of current antiretroviral therapy (cART). The cART treatment regimens dramatically improved life expectancy and mortality of patients with HIV-1 infection and AIDS. However, new and improved protease inhibitor drugs are essential for future treatment options. To this end, syntheses of optically active (3a<i>S</i>,4<i>S</i>,7a<i>R</i>)-hexahydro-4<i>H</i>-furo[2,3-<i>b</i>]pyran-4-ol, (3a<i>R</i>,4<i>R</i>,7a<i>S</i>)-hexahydro-4<i>H</i>-furo[2,3-b]pyran-4-ol, and (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-hexahydrofuro[2,3-6]furan-3-ol have been accomplished. These stereochemically defined heterocyclic derivatives are important high-affinity P2 ligands for a variety of highly potent HIV-1 protease inhibitors. The key steps for the synthesis hexehydrofuropyranol involve an efficient Paternò-Büchi [2+2] photocycloaddition, catalytic hydrogenation, acid-catalyzed cyclization to form the racemic ligand alcohol, and enzymatic resolution with immobilized Amano Lipase PS-30. Optically active ligand alcohols were obtained with high enantiomeric purity. Enantiomer (-)-ligand alcohol has been converted to potent HIV-1 protease inhibitors. <div><br></div><div>(3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-Hexahydrofuro[2,3-<i>b</i>]furan-3-ol(<i>bis</i>-tetrahydrofuran) is a key subunit of darunavir, an FDA approved HIV-1 protease inhibitor drug which is widely used for the treatment of HIV/AIDS patients. This stereochemically defined bicyclic heterocycle is also embedded in a variety of highly potent HIV-1 protease inhibitors. The synthesis of optically active <i>bis</i>-tetrahydrofuran was achieved in optically pure form utilizing commercially available and inexpensive 1,2-<i>O</i>-isopropylidene-α-D-xylofuranose or 1,2-O-isopropylidene-α-D-glucofuranose as the starting material. The key steps involve a highly stereoselective substrate-controlled hydrogenation of ethyl 2-(dihydrofuran-3(2H)-ylidene)acetate, a Lewis acid-catalyzed anomeric reduction of a 1,2-<i>O</i>-isopropylidene-protected glycofuranoside, and a Baeyer-Villiger oxidation of a tetrahydrofuranyl-2-aldehyde derivative. Optically active (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-hexahydrofuro[2,3-<i>b</i>]furan-3-ol ligand was converted to darunavir efficiently. Furthermore, both furopyranol and bis-tetrahydrofuran ligand alcohols have been converted into a variety of potent HIV-1 protease inhibitors including inhibitors containing P2'-boronic acid ligands.<br></div><div><br></div><div>Diabetes mellitus is a chronic, progressive metabolic disorder that seriously threatens human health worldwide, particularly in developing countries. The prevalence of diabetes has been increasing steadily, especially in developing countries. Carambolaflavone A is a natural flavonoid isolated from the leaves of starfruit tree, <i>Averrhoacarambola</i>, in 2005. Carambolaflavone A possesses a <i>C</i>-aryl glycosidic linkage. Carambolaflavone A exhibited significant antihyperglycemic properties. More detailed biological studies reveal that it can lower acute blood glucose. The biology and chemistry of carambolaflavone A attracted our interest in synthesis and further design of interesting structural variants. A convergent total synthesis of carambolaflavone A has been accomplished. The synthesis highlights a bismuth triflate-catalyzed stereoselective C-aryl glycosylation of flavan and an appropriately protected D-fucose derivative as the key step. The glycosylation partners were synthesized from commercially available (±)-naringenin and D-(+)-galactose, respectively. An oxidative bromination and elimination reaction sequence was utilized to construct the flavone. The natural product is obtained in 10 steps (longest linear sequence) from D-(+)-galactose.<br></div>