Peddy Vishweshwar

Crystal engineering of pharmaceutical co-crystals from polymorphic active pharmaceutical ingredients

The carboxylic acid-primary amide supramolecular heterosynthon is exploited for the generation of pharmaceutical co-crystals that contain two active pharmaceutical ingredients that are polymorphic in their pure forms.

Supramolecular synthon polymorphism in 2 : 1 co-crystal of 4-hydroxybenzoic acid and 2,3,5,6-tetramethylpyrazine

Co-crystals of 4-hydroxybenzoic acid and 2,3,5,6-tetramethylpyrazine (2 : 1) exhibit the first supramolecular synthon polymorphism in a co-crystal; metastable anti-hierarchic polymorph I converts to stable hierarchic form II.

Solid state structural studies of saccharin salts with some heterocyclic bases

Five saccharin salts with heterocyclic bases 1,2-bis(4-pyridyl)ethane, 1; trans-1,2-bis(4-pyridyl)ethylene, 2; piperazine, 3; 1,4-dimethylpiperazine, 4 and 2,2′-dipyridylamine, 5 have been synthesized and characterized by single crystal X-ray diffraction. The crystal structures reveal that in all the salts, the hydrogen atom has been transferred from saccharin nitrogen to the base nitrogen and sustained through charge-assisted hydrogen bonds. In salts 1–3, N+–H donor forms N+–H⋯O hydrogen bonds with the carbonyl oxygen of saccharinate, whereas it forms N+–H⋯N− in 4 and intramolecular N+–H⋯N in 5. Salts 2 and 3 also form weak N+–H⋯N−hydrogen bonds. Only in salt3, the SO2 moiety is involved in conventional hydrogen bonding.

Crystalline forms and aqueous solubilities of an IBS drug, tegaserod

Tegaserod is shown to exist in the tautomeric form II in the free base and also in a monohydrate. The Tegaserod nicotinate salt has a 6-fold better aqueous solubility than the marketed Tegaserod maleate (form A, Zelnorm™).

5-Meth­oxy-2,2-dimethyl-6-[(2E)-2-methyl­but-2-eno­yl]-10-phenyl-2H,8H-pyrano[2,3-f]chromen-8-one (calophyllolide)

The title compound, C26H24O5, was isolated from calophyllum inophyllum seeds. In the molecule, the phenyl and 2-methylbut-2-enoyl groups are almost orthogonal to the chromene fragment [C—C—C—C torsion angles = 81.4 (3) and −90.1 (2)°, respectively]. In the crystal packing, centrosymmetrically related molecules are linked by C—H⋯O contacts into dimers, which are connected via further C—H⋯O interactions into a double chain along [010].

(S)-3-(Ammoniomethyl)-5-methylhexanoate (pregabalin).

The title compound, C(8)H(17)NO(2), exists as a zwitterion, adopting a propeller conformation. Molecules self-assemble to form a hydrogen-bonded layer parallel to the ab crystallographic plane connected by N+-H...O- and C-H...O- hydrogen bonds. These layers are stacked along the c axis and are stabilized by van der Waals interactions.

(R)-(+)-2-{[(3-Methyl-4-nitro-pyridin-2-yl)meth-yl]sulfin-yl}-1H-benzimidazole.

The title compound, C14H12N4O3S, is an intermediate of Dexlansoprazole, a proton pump inhibitor (PPI) mainly developed for anti-ulcer activity. The absolute configuration of the title compound was determined as R. The crystal structure reveals that the molecules form chains along the b axis through N—H⋯N and C—H⋯O hydrogen-bonded dimers. These chains are connected via weak C—H⋯O hydrogen bonds.

(3S,4R)-4-(4-Fluoro-phen-yl)-3-(hydroxy-meth-yl)piperidinium chloride.

The title compound, C12H17FNO+·Cl−, is a degradation impurity of paroxetine hydrochloride hemihydrate (PAXIL), an antidepressant belonging to the group of drugs called selective serotonin reuptake inhibitors (SSRIs). Similar to the paroxetine hydrochloride salt with protonation having taken place on the basic piperidine ring, the degradation impurity also exists as the hydrochloride salt. The cyclic six-membered piperidinium ring adopts a chair conformation with the hydroxymethyl and 4-fluorophenyl groups in the equatorial positions. The ions form a tape along the b axis through charge-assisted N+—H⋯Cl− hydrogen bonds; these tapes are connected by O—H⋯Cl− hydrogen bonds along the a axis.

Alternative Synthesis and the Determination of Absolute Configuration of Docetaxel, an Anticancer Drug

Abstract A simple, efficient, and alternative synthetic route for docetaxel with better control on the protection–deprotection sequence has been developed. The process is easily scalable and commercially viable, and critical impurities can be controlled efficiently. For the first time, absolute configuration of docetaxel was determined unambiguously by single-crystal x-ray diffraction. GRAPHICAL ABSTRACT

1-[(4S)-4-Benzyl-2-thioxo-1,3-thia­zol­idin-3-yl]propan-1-one

The analysis of the title chiral auxiliary compound, C13H15NOS2, has enabled the determination of the absolute configuration at the benzyl-bearing ring C atom as S. In the crystal structure, molecules aggregate into helical chains along the b axis via C—H⋯O contacts.