Enantiomerically pure tertiary thiols provide a major synthetic challenge, and despite the importance of chiral sulfur-containing compounds in biological and medicinal chemistry, surprisingly few effective methods are suitable for the asymmetric synthesis of tertiary thiols. This review details the most practical of the methods available.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-7-68.pdf

Asymmetric synthesis of tertiary thiols and thioethers

Inclusion complexes are molecular compounds having the characteristic structure of an adduct, in which one compound (host molecule) spatially encloses another The enclosed compound (guest molecule) is situated in the cavity of the host without significantly affecting the host framework structure Apart from a slight deformation, it is a characteristic feature that the size and shape of the available cavity remain practically unaltered

Cyclodextrin Inclusion Complexes

5-Nitroisocoumarins from tandem Castro–Stephens coupling—6-endo-dig cyclisation of 2-iodo-3-nitrobenzoic acid and arylethynes and ring-closure of methyl 2-alkynyl-3-nitrobenzoates with electrophiles

Aggregation of the microtubule-associated protein Tau is a hallmark of Alzheimer's disease with Tau oligomers suspected as the most toxic agent. Tau is a client of the molecular chaperone Hsp90, although it is unclear whether and how the chaperone massages the structure of intrinsically disordered Tau. Using electron paramagnetic resonance, we extract structural information from the very broad conformational ensemble of Tau: Tau in solution is highly dynamic and polymorphic, although "paper clip"-shaped by long-range contacts. Interaction with Hsp90 promotes an open Tau conformation, which we identify as the molecular basis for the formation of small Tau oligomers by exposure of the aggregation-prone repeat domain to other Tau molecules. At the same time, formation of Tau fibrils is inhibited. We therefore provide the nanometer-scale zoom into chaperoning an amyloid client, highlighting formation of oligomers as the consequence of this biologically relevant interaction.

https://advances.sciencemag.org/content/advances/6/11/eaax6999.full.pdf

The mechanism of Hsp90-induced oligomerizaton of Tau

Culture extracts from the cave-derived actinomycete Nonomuraea specus were investigated, resulting in the discovery of a new S-bridged pyronaphthoquinone dimer and its monomeric progenitors designated hypogeamicins A–D (1–4). The structures were elucidated using NMR spectroscopy, and the relative stereochemistries of the pyrans were inferred using NOE and comparison to previously reported compounds. Absolute stereochemistry was determined using quantum chemical calculations of specific rotation and vibrational and electronic circular dichroism spectra, after an extensive conformational search and including solute–solvent polarization effects, and comparing with the corresponding experimental data for the monomeric congeners. Interestingly, the dimeric hypogeamicin A (1) was found to be cytotoxic to the colon cancer derived cell line TCT-1 at low micromolar ranges, but not bacteria, whereas the monomeric precursors possessed antibiotic activity but no significant TCT-1 cytotoxicity.

Structure and Stereochemical Determination of Hypogeamicins from a Cave-Derived Actinomycete.

The first total synthesis and structural determination of (+)-BE-52440A

Competitive inclusion in β-cyclodextrin between 4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy and chloro-substituted acetic acids has been monitored by esr spectroscopy. The temperature dependence of the rotational correlation frequencies calculated by Kivelson's equation, using esr spectra of the radical, suggests that a structural change of β-cyclodextrin occurs at about 30 °C and that trichloroacetic acid is included extensively at 20–35 °C, but significant inclusion of acetic acid is not observed. The degree of competitive inclusion is in the order of trichloro, dichloro, and monochloroacetic acids over the range of 20–80 °C. Carbon-13 nmr studies also prove the inclusion of trichloroacetic acid showing an inclusion shift of the trichloromethyl carbon by 1.4 ppm.

Competitive inclusion of chloro-substituted acetic acids into β-cyclodextrin monitored by rotational correlation frequencies of 4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy radical

The rate of the decarboxylation of trichloroacetic acid (abbreviated as TCAH) in the presence of β-cyclodextrin(βCD) in an aqueous solution of sodium hydroxide has been followed by the determination of the remaining TCAH. The rate equation was given by Rate=(k_1T+k_1TCC_βCD)C_TCAH^1/2+(k_2T-k_2TCC_βCD)C_TCAH. A probable bimolecular decarboxylation mechanism which involves the unionized molecule of TCAH rather than the anion was proposed and discussed.

The Kinetics of the β-Cyclodextrin-catalyzed Decarboxylation of Trichloroacetic Acid in an Alkaline Solution

An identification of quaternary ammonium salts formed as a quasi-stable intermediate in the course of the triethylenediamine-catalyzed aminolysis of phenyl N-phenylcarbamates with aniline was performed by UV spectroscopic measurements and semiempirical ASMO-SCF calculations.

Yoshiaki Furuya

Papers

The first total synthesis and structural determination of (+)-BE-52440A

Competitive inclusion of chloro-substituted acetic acids into β-cyclodextrin monitored by rotational correlation frequencies of 4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy radical

The Kinetics of the β-Cyclodextrin-catalyzed Decarboxylation of Trichloroacetic Acid in an Alkaline Solution

Quaternary ammonium salts as a quasi-stable intermediate in triethyleneliamine-catalyzed aminolysis of phenyl n -phenylcarbamates with aniline

Tertiary Amine-Catalyzed Transesterification of Methyl p-Nitrobenzoate