L. E. Nikitina

Monoterpenoids Dithiophosphates. Synthesis and Biological Activity

O,O-Dialkyldithiophosphoric acids adds at the double bond of the racemic camphene and (+)- limonene in the presence of Lewis acids in accordance with the Markownikoff rule with the formation of Sterpenyl esters of dithiophosphoric acids. The reaction with camphene is accompanied by the rearrangement of camphane structure to that of bornane. Addition of dithiophosphoric acid to (+)-limonene proceeds with the participation of the exocyclic double bond. Toxic and genotoxic properties of the monoterpenoid dithiophosphates were studied.

Synthesis and antifungal activity of compounds of the pinane series

New terpenyl sulfides of the pinane series have been synthesized from (-)-β-pinene, cis- and trans-verbenols, and myrtenol. Screening for antifungal activity of the monoterpenoids of the pinane series has been carried out. The relationship between the structure and antifungal properties of the synthesized compounds has been established.

Study of “Racemic Compound-Like” Behavior of Diastereomeric Mixture of Pinanyl Sulfoxides by X-Ray Diffraction, IR Spectroscopy, and DFT Calculations

Abstract The oxidation of a β-hydroxysulfide in the pinane series by use of m-chloroperbenzoic acid resulted in the formation of the corresponding β-hydroxysulfoxide as a mixture of two diastereomers in 4:5 ratio. According to single-crystal X-ray diffraction (XRD) results, it is established that the diastereomeric mixture of sulfoxides crystallizes in the “racemic compound-like” manner under formation of asymmetric dimers through S=O··H–O interactions. This asymmetric dimer formed from diastereomeric molecules is a structural unit in both crystal modifications, the triclinic and the monoclinic one. The behavior of the diastereomeric mixture of pinane derived sulfoxides in crystals, melts and in tetrachloromethane solutions was studied by IR spectroscopy. The density functional theory (DFT) method with 6-31G (d, p) basis set was used to calculate the optimized geometrical parameters and vibrational frequencies of different associates in solutions. The calculated vibrational frequencies are compared with experimental IR spectra. GRAPHICAL ABSTRACT

A new polymorph of methimazole: Single crystal and powder X-ray diffraction study

A new polymorph of 1-methyl-4-imidazoline-2-thione has been first discovered and studied by X-ray diffraction. The crystal of the new polymorph is monoclinic, the asymmetric part of the cell contains three independent molecules. In the crystal, the key compound is in the form of planar hydrogen-bonded dimers due to the interactions of the N-H…S type. The new modification is of an intensely yellow color in contrast to the previously known colorless forms, is characterized by a lower density but stronger hydrogen bonds; it is formed as a minor impurity to main triclinic polymorph.

Synthesis and antifungal activity of monoterpenoids of the carane series

The antifungal activity of terpenoids of the carane series was studied; an interaction was found between the structures of these compounds and their antifungal properties. The actions of several terpenoids on the adhesive activity and enzyme systems of the fungus Candida albicans were studied.

Antifungal activity of bicyclic monoterpenoids and terpenesulfides

A total of 33 compounds including bicyclic monoterpenes, oxides, allyl alcohols, and S-containing pinane and carane derivatives were screened for antifungal activity against mycelial and yeast-like fungi. The structure–activity relationship was studied. The most active antimycotics were found.

SULFUR-CONTAINING DERIVATIVES OF MONO- AND BICYCLIC NATURAL MONOTERPENOIDS

Examples of thiylation of natural mono- and bicyclic and variously functionalized monoterpenoids (alkenes, ketones, epoxides, alcohols) and the latest transformation pathways of the newly formed sulfur-containing derivatives were reviewed.

When two symmetrically independent molecules must be different: “Crystallization-induced diastereomerization” of chiral pinanyl sulfone

According to X-ray data, homochiral pinanyl sulfone crystallizes as an asymmetric dimer formed by pairwise H-bonds involving stereochemically different oxygen atoms of sulfonyl groups of molecules A and B. Thus, a pro-R atom is invoked for the construction of a relevant H-bond in molecule A, but in the case of molecule B only a pro-S atom is involved. Newly formed chiral sulfur atoms take opposite chirality in molecules A and B, while the configuration of the pinane skeleton remains unchanged. Such a stereochemical transformation is called “crystallization-induced diastereomerization”. The stability of the asymmetric dimer found in the crystal was evaluated within the framework of DFT (B3LYP, 6-31G (d,p)) and studied via IR spectroscopy in solution.

Addition of thiols to (-)-carvone

Polyfunctional thioterpenoids were formed in the presence of a Lewis-acid catalyst by reaction of (-)-carvone with thiols that involved the endocyclic double bond and the carbonyl.

S=o…s=o Interactions as a Driving Force for Low-Temperature Conformational Rearrangement of Stable H-Bonding {S(O)-Ch2-Ch2-OH···}2 Synthon in two Modifications of Diastereomeric Pinanyl Sulfoxides Co-Crystal

GRAPHICAL ABSTRACT For the triclinic and monoclinic modifications of diastereomeric pinanyl sulfoxides co-crystal, remarkable alterations in unit cell parameters by transition from 293 to 150 К were ascertained. Such alterations are accompanied by conformational restructuring of a stable hydrogen-bonded synthon from an “unfolded” to a “folded” form. The driving force of this restructuring is the tendency to form S=O…S=O interactions, which show up in the low-temperature phases of both polymorphs. These are well-supported by the methods of quantum chemistry (DFT, B97-D/6-31G(d,p), AIM All).