Project description:The 20-membered marine macrodiolide clavosolide A is prepared in 7 steps (LLS) in the absence of protecting groups or chiral auxiliaries via enantioselective alcohol-mediated carbonyl addition. In 9 prior total syntheses, 11-34 steps (LLS) were required.
Project description:A total synthesis of the oxo-polyene macrolide (+)-roxaticin is achieved in 20 steps from 1,3-propanediol. In this approach, 9 of 10 C-C bonds formed in the longest linear sequence are made via metal catalysis, including 7 C-C bonds formed by iridium catalyzed alcohol C-C coupling. Notably, the present synthesis, which represents the most concise preparation of any oxo-polyene macrolide reported to date, is achieved in the absence of chiral reagents and chiral auxiliaries with minimal use of premetalated C-nucleophiles.
Project description:The C(21)-C(40) fragment of fibrinogen receptor inhibitor tetrafibricin was prepared in 12 steps from propane diol (longest linear sequence). In this approach, 6 C-C bonds are formed via asymmetric iridium catalyzed transfer hydrogenative carbonyl allylation and 2 C═C bonds are formed via Grubbs olefin cross-metathesis.
Project description:New chiral regioisomeric γ-hydroxyphosphine ligands were synthesized from α-pinene. The key transformation was the thermal [2,3]-sigmatropic rearrangement of allyldiphenylphosphinites, obtained from (1R,2R,4S,5R)-3-methyleneneoisoverbanol and (1R,2R,3R,5R)-4-methyleneneoisopinocampheol, to allylphosphine oxides. Hydroxy groups were introduced stereoselectively through a hydroboration-oxidation reaction proceeding from the less hindered site providing a trans relationship between the hydroxy and the phosphine substituents.
Project description:The key stereochemical factors that determine transfer of asymmetry from the chiral auxiliary to the cyclopentenone in the allene ether version of the Nazarov reaction have been elucidated. On the basis of the new insights into the mechanism, two highly effective chiral auxiliaries were designed and prepared.
Project description:Lithium enolates derived from carboxylic acids are ubiquitous intermediates in organic synthesis. Asymmetric transformations with these intermediates, a central goal of organic synthesis, are typically carried out with covalently attached chiral auxiliaries. An alternative approach is to utilize chiral reagents that form discrete, well-defined aggregates with lithium enolates, providing a chiral environment conducive of asymmetric bond formation. These reagents effectively act as noncovalent, or traceless, chiral auxiliaries. Lithium amides are an obvious choice for such reagents as they are known to form mixed aggregates with lithium enolates. We demonstrate here that mixed aggregates can effect highly enantioselective transformations of lithium enolates in several classes of reactions, most notably in transformations forming tetrasubstituted and quaternary carbon centers. Easy recovery of the chiral reagent by aqueous extraction is another practical advantage of this one-step protocol. Crystallographic, spectroscopic, and computational studies of the central reactive aggregate, which provide insight into the origins of selectivity, are also reported.
Project description:Homoallylic alcohols are oxidized to β-hydroxy ketones using a TBHP-mediated Pd-catalyzed Wacker-type oxidation. The use of a bidentate ligand, quinoline-2-oxazoline (Quinox), and TBHP((aq)) as the terminal oxidant provides good yields of the desired products with reaction times significantly reduced as compared to the Tsuji-Wacker oxidation. Additionally, bis- and tris-homoallylic alcohols are oxidized to provide cyclic peroxyketals, presumably via nucleophilic attack of the methyl ketone product.
Project description:In traditional oligodeoxynucleotide (ODN) synthesis, phosphate groups are protected with the 2-cyanoethyl group, and amino groups are protected with acyl groups. At the end of ODN synthesis, deprotection is achieved with strong bases and nucleophiles. Therefore, traditional technologies are not suitable for the synthesis of ODNs containing sensitive functionalities. To address the problem, we report the use of Dim and Dmoc groups, which are based on the 1,3-dithian-2-yl-methyl function, for phosphate and amine protection for the solid phase ODN synthesis. Using the new Dim-Dmoc protection, deprotection was achieved under mild oxidative conditions without using any strong bases and nucleophiles. As a result, the new technology is suitable for the synthesis of ODNs containing sensitive functions. To demonstrate feasibility, seven 20-mer ODNs including four that contain sensitive ester and alkyl chloride groups were synthesized, purified with RP HPLC, and characterized with MALDI-TOF MS and enzyme digestion essays. High purity ODNs were obtained.
Project description:Accessible drug modalities have continued to increase in number in recent years. Peptides play a central role as pharmaceuticals and biomaterials in these new drug modalities. Although traditional peptide synthesis using chain-elongation from C- to N-terminus is reliable, it produces large quantities of chemical waste derived from protecting groups and condensation reagents, which place a heavy burden on the environment. Here we report an alternative N-to-C elongation strategy utilizing catalytic peptide thioacid formation and oxidative peptide bond formation with main chain-unprotected amino acids under aerobic conditions. This method is applicable to both iterative peptide couplings and convergent fragment couplings without requiring elaborate condensation reagents and protecting group manipulations. A recyclable N-hydroxy pyridone additive effectively suppresses epimerization at the elongating chain. We demonstrate the practicality of this method by showcasing a straightforward synthesis of the nonapeptide DSIP. This method further opens the door to clean and atom-efficient peptide synthesis.
Project description:Nanocolloids that are cumulatively referred to as nanocarbons, attracted significant attention during the last decade because of facile synthesis methods, water solubility, tunable photoluminescence, easy surface modification, and high biocompatibility. Among the latest development in this reserach area are chiral nanocarbons exemplified by chiral carbon dots (CDots). They are expected to have applications in sensing, catalysis, imaging, and nanomedicine. However, the current methods of CDots synthesis show often contradictory chemical/optical properties and structural information that required a systematic study with careful structural evaluation. Here, we investigate and optimize chiroptical activity and photoluminescence of L- and D-CDots obtained by hydrothermal carbonization of L- and D-cysteine, respectively. Nuclear magnetic resonance spectroscopy demonstrates that they are formed via gradual dehydrogenation and condensation reactions of the starting amino acid leading to particles with a wide spectrum of functional groups including aromatic cycles. We found that the chiroptical activity of CDots has an inverse correlation with the synthesis duration and temperature, whereas the photoluminescence intensity has a direct one, which is associated with degree of carbonization. Also, our studies show that the hydrothermal synthesis of cysteine in the presence of boric acid leads to the formation of CDots rather than boron nitride nanoparticles as was previously proposed in several reports. These results can be used to design chiral carbon-based nanoparticles with optimal chemical, chiroptical, and photoluminescent properties.