Tzenge-Lien Shih

The use of tetramethylguanidinium azide in non-halogenated solvents avoids potential explosion hazards

Tetramethylguanidinium azide was used in the quantitative conversion of glycosyl halides 1 – 5 to the corresponding glycosyl azides 10 – 14. The stereoselective reactions occurred with complete inversion at the anomeric centers. The titled reagent was also employed in the selective synthesis of pseudoglycosyl azide 16 and two steroidal azides 17 and 18. All reactions were carried out in non-halogenated solvents to avoid potential explosion hazards.

Enantiotropic Nematics From Cross‐Like 1,2,4,5‐Tetrakis(4′‐alkyl‐4‐ethynylbiphenyl)benzenes and Their Biaxiality Studies

The theoretically predicted optimum length/breadth/width ratio for maximizing shape biaxiality was investigated experimentally by the facile and successful synthesis of cross-shaped compound 3, which showed enantiomeric nematic phase behavior. This cross-like core structure could alternatively be viewed as two fused V-shaped mesogens, which have recently immerged as a new direction in biaxial nematic research, at the bending tips that can act as a new structure for biaxial investigations. Whilst the thermal analysis data of compound 3 did not meet the expected theoretical values for biaxial nematics, surface-induced biaxiality was evidenced by optical studies. Cluster-size analysis within the nematic phase of compound 3 revealed the formation of meta-cybotactic nematics, which approached the cluster sizes of cybotactic nematics. The split small-angle 2D X-ray diffraction patterns of magnetic-field-aligned samples indicated that the nematic phase was composed of small smectic C-like clusters with the tilting of molecules within the clusters. The wide-temperature-range enantiomeric nematic phase of cross-like compound 3 enabled the molecular skeleton to serve as an alternative skeleton to bent-rod mesogens, which exhibited nematic phases with the potential competition of transitions to higher-order liquid-crystalline phases and crystallization, for future biaxial investigations.

Synthesis of polyhydroxy 7- and N-alkyl-azepanes as potent glycosidase inhibitors

An effective synthetic method for polyhydroxylated azepanes that contain an alkyl group (Me or Bu) at either the 7- or N-positions is developed. The synthetic routes are accomplished in eight to ten steps from d-(-)-quinic acid. Among the compounds synthesized, the polyhydroxy 7-butyl azepane (compound 3), which possessed the R-configuration at C-7 position, is shown to give potent inhibition against β-galactosidase (IC(50)= 3 microM). Preliminary biological data indicate that the length of alkyl groups along with the proper stereochemistry at the C-7 position is essential for acquiring extra binding affinity. Using similar synthetic routes, the polyhydroxy N-methyl and N-butyl azepanes are synthesized for the comparison of their biological activities.

Efficient syntheses of (−)-shikimate and (−)-quinate 3-phosphate via trans vicinal diol protection with 2,2,3,3-tetramethoxybutane (TMB) of shikimic and quinic acids

Abstract (−)-Shikimate 3-phosphate and (−)-quinate 3-phosphate can be synthesized by selective protection of their trans diol functionality using 2,2,3,3-tetramethoxybutane (TMB) using d -(−)-shikimic acid and d -(−)-quinic acid as starting materials. This versatile reagent facilitates the synthesis of these important biological targets in fewer steps than previously reported. By the proper choice of protecting group for C-3 hydroxyl in d -(−)-quinic acid, it can be converted to a key intermediate in the synthesis of (−)-shikimate 3-phosphate.

Synthesis of a New Family of Aminocyclitols from D-(-)-Quinic Acid

Abstract In continuation of our interest in the synthesis of glycosidase inhibitors, we report herein an efficient synthesis of three new polyhydroxylated amino cyclohexane derivatives (aminocyclitols) that may potentially possess important biological activities. The key step involved the highly stereoselective dihydroxylation of protected azido cyclohexene derivatives 5, 9, and 15, which were easily red from D-(-)-quinic acid. The subsequent hydrogenation step was conducted under acidic conditions to provide the target molecules in an efficient manner with high overall yields.

Single-component room-temperature discotic nematic liquid crystals formed by introducing an attraction-enhancing in-plane protrusion onto the hexa(phenylethynyl)benzene core

Single-component room-temperature discotic nematics have been achieved within large temperature ranges by introducing an attraction-enhancing protrusion onto hexa(phenylethynyl)benzenes. X-ray diffraction investigations revealed the nematic phases of these new discotic nematic materials to be cybotactic.

Regioselectivity in the Ring Opening of Epoxides for the Synthesis of Aminocyclitols from D-(-)-Quinic Acid

Efficient syntheses of four aminocyclitols are reported. Each synthesis is accomplished in eight steps starting from D-(−)-quinic acid. The key step involves a highly regioselective ring opening of epoxides by sodium azide.

Epoxidation of Protected (1,4,5)‐Cyclohex‐2‐ene‐triols and Their Acid Hydrolysis to Synthesize Quercitols from D‐(−)‐Quinic Acid

Abstract Highly stereoselective epoxidations have been achieved in both cyclohexylidene acetal and butane 2,3‐bisacetal (BBA) protection of (1,4,5)‐cyclohex‐2‐ene‐triols. These epoxy derivatives are all derived from D‐(−)‐quinic acid and can be used for the synthesis of muco‐, (+)‐epi‐, (+)‐vibo, (−)‐talo, and (−)‐gala‐quercitols.

Expeditious Synthesis of New 3,4,6‐Trihydroxythiepanes from d‐(‐)‐Quinic Acid

Abstract We report herein that the new seven‐membered‐ring thiosugars (thiepanes) have been synthesized from d‐(‐)‐quinic acid. The key feature of the synthesis involves the thiocyclization of protected hexane‐1,2,3,5,6‐pentanol derivatives. The subsequent step of acidic removal of protecting groups is critical in the reaction conditions to obtain the required 3,4,6‐trihydroxythiepanes. During the course of studies, the unexpected trihydroxythiopyrans are formed because of the ring contractions of their corresponding trihydroxythiepanes under various conditions.

From Carbohydrates to the Discovery of Pronounced Heteroatomic Effects on Anionically Accelerated [3,3]-Sigmatropic Rearrangements

The (Z)-(iodovinyl)oxetane 12 was prepared from D-glucose and the acyclic analog 18 was obtained from D-mannitol. Following the generation of their lithium derivatives by halogen−metal exchange, coupling to the enantiopure vinyl-substituted norbornanones 20, 23, and 29 proceeded exclusively via endo attack to deliver the targeted exo-carbinols. The anionic oxy-Cope rearrangements of 21 and 24 were seen to differ appreciably in rate. While the sulfur derivative 24 experiences [3,3] sigmatropy with a half-life of less than a minute at −78 °C, its oxygen analogue 21 proved unreactive below −20 °C under entirely comparable conditions. This phenomenon is critically examined in a synthetic context involving 26 and 30, where the heavily functionalized acyclic side chain involved previously is supplanted by an oxetane assembly. In the sulfur example, isomerization occurs very rapidly as before with 100% transfer of chirality. The kinetic response of vinyl ether 26 now proved to be entirely comparable. However, the pathway followed in this instance was intramolecular nucleophilic attack by the “naked” alkoxide at the less substituted C−O bond of the oxetane with ring cleavage and formation of alcohol 28. The global findings provide a glimpse of the subtle way in which [3,3]-sigmatropic transpositions can be modulated by heteroatomic substitution.