Instytut Farmaceutyczny

Siec Badawcza Lukasiewicz-instytut Chemii Przemyslowej Imienia Profesora Ignacego Moscickiego

Nattopharma R & D Ltd.

Jerzy Winiarski

Andrzej Kutner

Wieslaw Szelejewski

Marek Kubiszewski

Marcin Cybulski

Oliwia Zegrocka-Stendel

Hanna Fitak

Jacek Martynow

Marek Napiórkowski

Michal Chodyński

Agnieszka Burzynska-Prajzner

Teresa Ryznar

Piotr Golebiewski

Krzysztof Wiśniewski

Bartlomiej Górecki

Osman Achmatowicz

Julita Szyc

Agnieszka Burzyńska

Aneta Baj

Katarzyna Sidoryk

Lukasz Jedynak

Dorota Pietrzkowska

Konrad Zielinski

Krzysztof Krajewski

Jadwiga Dzikowska

Regina Gutowska

Łukasz Jedynak

Jacek Morzycki

Stanislaw Witkowski

Piotr Wałejko

Piotr Walejko

Marek Napiorkowski

Marek NAPIÓRKOWSKI

Provided is an improved process of vitamin K2 derivatives preparation, represented by formula (I) wherein n is an integer from 3 to 13. 

Process of vitamin Kderivatives preparation

Process for preparation of MK-7 type of vitamin K2 is characterized by attaching hexaprenyl chain of 'all-trans' configuration to monoprenyl derivative of menadiol following '1+6' synthetic strategy. According to the invention, a-sulfonyl carbanion generated in situ from the protected monoprenyl menadiol of the formula (II), wherein Rrepresents C-alkyl group, is reacted with hexaprenyl halide of the formula (VII), wherein X represents halogen atom, preferably bromine, both Z' and Z&#x2032; represent H or one of Z&#x2032; and Z&#x2033; represents H and the other represents phenylsulfonyl group &#x2014;SOPh in the alkylation reaction. The hexaprenyl halide of formula (VII) is obtained by coupling two triprenyl units in alkylation reaction, with or without separation of the intermediates. 

Process for preparation of MK-7 type of vitamin K2

The invention relates to a process for the preparation of 13,14-dihydro-PGFderivatives of R or S configuration at carbon 15, represented by the general formula (I), wherein the identity of the substituents is defined in the description. Compounds of the formula (I) are valuable biologically-active substances or intermediates in the preparation thereof. The invention especially relates to the process for preparation of 13,14-dihydro-15(R)-17-substituted-18,19,20-trinor-PGF, i.e., latanoprost.

Process for preparation of 13,14-dihydro-PGF2 alpha derivatives

A process for the preparation of a pharmaceutical-grade anhydrous calcipotriol comprising: (a) dissolving crude calcipotriol having a water content of X% by weight in a first solvent or in a mixture of two or more first solvents, said first solvent or said mixture of two or more first solvents forming an azeotropic system with water, to obtain a solution of crude calcipotriol; (b) obtaining an intermediate calcipotriol by (i) placing said solution of crude calcipotriol under a reduced pressure and evaporating, if X is greater than or equal to 1, or (ii) crystallizing, if X is lower than 1; and (c) re-dissolving said intermediate calcipotriol in a second solvent or a mixture of two or more second solvents, said second solvent being anhydrous, and crystallizing at least once to obtain pharmaceutical-grade anhydrous calcipotriol.

Process for preparation of pharmaceutically pure anhydrous calcipotriol

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Warsaw, Poland

Jerzy Winiarski