Wyniki wyszukiwania - BazTech

1

Hormony steroidowe, leki przeciwzapalne, pigułki antykoncepcyjne. związki i ludzie : notatki historyczne (część 1 i 2)

Wicha Jerzy

Wiadomości Chemiczne

|

2021

|

[Z] 75, 5-6

677--753

EN

A short historical outlook of steroid hormones isolation, structure elucidation and hormonal drugs development following by a survey of contraceptive therapeutics syntheses and advancements is given. Structural evolution of the first pills, “the pill”, to the presently used oral contraceptives for women is scrutinized. Comments on activities of selected major researchers in the field: Josef Fried, Russell E. Marker, Arthur J. Birch, Carl Djerassi, Georgy G. Pincus, M. C. Chang, John Rock, Igor V. Torgov, Zoltan G. Hajos and Herchel Smith from the personal prospect are presented. Steroid sex hormones, estrogens (female), androgens (male) and gestagens (progesterone, pregnancy hormone) were isolated and identified as chemical entities in 20-tiest and 30-ties of the 20th century. Development of partial synthesis of basic hormones from cholesterol made possible the initial steroid drugs production: Testosterone propionate and 17a-Methyltestosterone (Ciba) as well as Proviron, Progynon, Proluton (Schering AG). In 1940th and 1950th corticosteroids were isolated and recognized as “magic” anti-inflammatory and antiarthritic drugs. Growing demand for antiarthritic drugs in 1950th stimulated search for new corticosteroid analogues and new steroid row materials. Exploration of Mexican plant Dioscorea “cabeza” by Synthex SA provided economical starting material, diosgenin, and opened the new prospects for hormonal drug research and the production. Subsequently, highly active corticosteroid analogues were developed by several pharmaceutical companies and 19-norprogesterone analogues of high gestagenic activity were synthesized - Norethisterone (Synthex) and Norethyndrel (Searle). Complex studies on the application of Norethyndrel as oral contraceptive for women were carried out in the Worcester Foundation for Experimental Biology. In 1959 the first drug “the pill”, which was developed on the grounds of Searls’ Norethyndrel - Enovid was registered by Food and Drug Administration in the USA. Shortly after that Norlutin, based upon Synthex’s Norethisterone, had also been approved for application. Commercial success of “the pill”, Enovid and Norlutin, triggered a broad research aimed at the partial synthesis and application of related progesterone analogues. In the end of 1950th and the beginning of 1960th the total synthesis of estrogens and 19-norsteroids gained practical importance. On these grounds Norgestrel and its active enancjomer Levonorgestrel were developed and commercialized by Wyeth Laboratories Inc. in the USA as the first contraceptive products by total synthesis. Starting from 1970th medicinal applications of corticosteroids gradually diminished, whereas growing attention was given to the development of hormonal contraceptives suitable for general application. Several synthetic modifications of Norethisterone and Levonorgestrel were developed and produced in a large scale. Another class of oral contraceptives stem from the steroid total synthesis developed in the Russell Uclaf laboratories. Structurally these compounds are characterized by 19-norsteroid core and the presence of bulky substituent at the position 11ß, as 4-(N,N-dimethylamino)phenyl- in Mifepristone (RU 486). The synthesis of 19-norpregnane derivatives bearing at the position 11ß various large aromatic or alphatic groups, which currently is receiving a great deal of attention, is considered.

2

Asymetryczna reakcja aldolowa: część II - katalityczna asymetryczna reakcja aldolowa w środowisku wodnym

Paradowska J., Rogozińska M., Młynarski J.

Wiadomości Chemiczne

|

2010

|

[Z] 64, 7-8

599-627

EN

Asymmetric organometallic and organocatalytic processes in aqueous systems are currently of great interest. A few years ago, only a few practitioners studied the subject; now organic reactions in water have become one of the most exciting research areas. Nature has perfected the stereospecific aldol reaction by using aldolase enzymes. While virtually all the biochemical aldol reactions use unmodified donor and acceptor carbonyls and take place under catalytic control in an aqueous environment, the chemical domain of the aldol addition has mostly relied on prior transformation of carbonyl substrates, and the whole process traditionally is carried out in anhydrous solvents. The area of asymmetric aldol reactions in water has received much attention recently in light of the perception of both its green chemistry advantages and its analogy to eon-perfected enzyme catalysis. Only recently catalytic asymmetric reactions promoted by water-compatible Lewis acids with chiral ligands have been developed; most Lewis acids are not stable in water. Seminal work by List, Lerner, and Barbas on the intermolecular proline-catalyzed direct asymmetric aldol reaction opened a new platform for designing metal-free asymmetric catalysts, although their application was initially limited to organic solvents. Most recently, the challenge of developing efficient aqueous-phase organocatalytic processes has also been tackled. Recent progress in the area initiated constructive discussion on the role and practical merits of water as a solvent. This article describes recent developments in this area.

3

Asymetryczna reakcja aldolowa : część I - nowe koncepcje, katalizatory i ich praktyczne zastosowanie w syntezie produktów naturalnych

Stodulski M., Młynarski J.

Wiadomości Chemiczne

|

2010

|

[Z] 64, 5-6

435-465

EN

The aldol reaction is one of the most important method for the stereoselective construction of polyketide natural products in both – living organisms and laboratory. The tremendous development in this field has led to development of many new variants of the aldol addition. There has been some success in the use of asymmetric catalysts, although they normally rely on a Mukaiyama-type process. This reaction required a conversion of a donor substrate into more reactive species such as enol silyl ether using not less than stoichiometric amounts of a silicon reagent and a base. From atom economic perspectives, such stoichiometric amounts of reagents should be excluded from the procedures. An exciting challenge in enhancement of the efficiency of the aldol reaction is to find a compound that will catalyze direct aldol addition without pre-formation of a nucleophile and to do so asymmetrically. Direct asymmetric aldol reaction, catalyzed by both metallic complexes and purely organic molecules now becomes one of the most desired tools in organic chemistry. After an initial period of validating methodology by using a wide range of important model reactions, the time has now been reached to address specific synthesis and solve pending problems of practical relevance. In this review we describe recently discovered, most important and most flexible catalysts for direct asymmetric aldol reaction and their application in total synthesis of target natural products and known compounds of biological and pharmaceutical relevance.