A5067762072- Vitamin D Research Studies
- Estrogen and related hormone effects
- Biotin and Related Studies
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Fluorine in Organic Chemistry
- Steroid Chemistry and Biochemistry
- Cyclopropane Reaction Mechanisms
- Click Chemistry and Applications
- Synthesis and Reactivity of Heterocycles
- Biochemical and Molecular Research
- Vitamin C and Antioxidants Research
- Hormonal Regulation and Hypertension
- Carbohydrate Chemistry and Synthesis
- Eicosanoids and Hypertension Pharmacology
- Crystallography and molecular interactions
- Synthesis and Reactions of Organic Compounds
- Growth Hormone and Insulin-like Growth Factors
- Organic Chemistry Cycloaddition Reactions
- Pharmacological Effects and Toxicity Studies
- Carbon dioxide utilization in catalysis
- Oxidative Organic Chemistry Reactions
- Bioactive Compounds and Antitumor Agents
- Synthesis and Biological Evaluation
- Adrenal Hormones and Disorders
University of Warsaw
2015-2024
Faculty (United Kingdom)
2019
University of Wisconsin–Madison
2006-2015
Ardent Sound (United States)
2004
Woods Hole Oceanographic Institution
2002
University of Białystok
1998
University of Wisconsin System
1988-1994
The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that best known because it mediates the actions of polycyclic and halogenated aromatic environmental toxicants such as 3-methylcholanthrene 2,3,7,8-tetrachlorodibenzo- p -dioxin. We report here successful identification an endogenous ligand for this receptor; ≈20 μg was isolated in pure form from 35 kg porcine lung. Its structure deduced 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester extensive...
CYP11A1 and CYP27A1 hydroxylate tachysterol3, a photoproduct of previtamin D3, producing 20S-hydroxytachysterol3 [20S(OH)T3] 25(OH)T3, respectively. Both metabolites were detected in the human epidermis serum. Tachysterol3 was also serum at concentration 7.3 ± 2.5 ng/ml. 20S(OH)T3 25(OH)T3 inhibited proliferation epidermal keratinocytes dermal fibroblasts stimulated expression differentiation anti-oxidative genes similar manner to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. They acted on vitamin...
New highly active isomers of the natural hormone 1α,25-dihydroxyvitamin D3 possessing an exomethylene group at 2-position were prepared in a convergent manner, starting with (−)-quinic acid and corresponding (20R)- (20S)-25-hydroxy Grundmann ketones. These 2-methylene-19-norvitamins efficiently converted to 2-methyl 2-hydroxymethyl derivatives, some which exhibited pronounced vivo biological activity. Configurations A-ring substituents determined by 1H NOE difference spectroscopy as well...
Novel 19-nor analogues of 1α,25-dihydroxyvitamin D3 were prepared and substituted at C-2 with an ethylidene group. The synthetic pathway was via Wittig−Horner coupling the corresponding A-ring phosphine oxides protected 25-hydroxy Grundmann's ketones. Selective catalytic hydrogenation 2-ethylidene provided 2α- 2β-ethyl compounds. 2-ethylidene-19-nor compounds a methyl group from moiety in trans relationship to C(6)−C(7) bond (E-isomers) more potent than Z-isomers natural hormone binding...
In a search for novel vitamin D compounds of potential therapeutic value, E- and Z-isomers 1α,25-dihydroxy-2-(3'-hydroxypropylidene)-19-norvitamin D3, as well derivative the former compound possessing 3'-(methoxymethoxy)propylidene substituent at C-2, were efficiently prepared. All vitamins obtained in convergent syntheses, starting with (−)-quinic acid protected 25-hydroxy Grundmann ketones. Quinic was converted into keto lactone 11, substituted hydroxypropylidene group attached by Wittig...
Since the discovery of active metabolite vitamin D, i.e., 1α,25-dihydroxyvitamin D 3 , there has been a continuous effort to synthesize analogs able carry out many functions native hormone without raising serum calcium concentration. The present report provides series previously undescribed wherein this goal is realized. We have prepared 2-methylene-19-nor-1α-hydroxyvitamin 1,25-(OH) 2 that possess only two four carbons side chain hydroxyl thereon. Compared these are slightly less in binding...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel convergent synthesis of side-chain-modified analogs 1.alpha.,25-dihydroxycholecalciferol and 1.alpha.,25-dihydroxyergocalciferolAndrzej Kutner, Kato L. Perlman, Amparo Lago, Heinrich K. Schnoes, H. F. DeLuca, Rafal R. SicinskiCite this: J. Org. Chem. 1988, 53, 15, 3450–3457Publication Date (Print):July 1, 1988Publication History Published online1 May 2002Published inissue 1 July...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and Biological Activity of 2-Hydroxy 2-Alkoxy Analogs 1.alpha.,25-Dihydroxy-19-norvitamin D3Rafal R. Sicinski, Kato L. Perlman, Hector F. DeLucaCite this: J. Med. Chem. 1994, 37, 22, 3730–3738Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://doi.org/10.1021/jm00048a009Request reuse permissionsArticle Views303Altmetric-Citations48LEARN ABOUT THESE METRICSArticle...
1α,25-Dihydroxy-18-norvitamin D3 and 1α,25-dihydroxy-18,19-dinorvitamin were prepared via Wittig−Horner coupling of 25-hydroxy-18-nor Grundmann type ketone with the corresponding A-ring phosphine oxides. Configuration at C-13 in 18-nor alcohol (C,D-ring synthon), obtained by oxidative degradation vitamin D3, was determined 1H NMR spectroscopy molecular mechanics calculations. Additional proof assigned trans-C/D-junction key intermediate follows from its chiroptical properties (circular...
To establish the conformation of vitamin D compounds responsible for biological activity, a 1alpha,25-dihydroxy-19-norvitamin analogue 4 possessing 1alpha-hydroxy group fixed in axial orientation (beta-chair form) was synthesized. The starting were bicyclic lactones 6, 7a, and 7b, derived from quinic acid lactone, which converted to ketone 13. Julia coupling this compound with sulfone 15 produced 19-norvitamin 4, an additional ring connecting 3beta-oxygen C-2, isomeric 3beta-hydroxy 5. In...
Two novel vitamin D analogues of the hormone 1α,25-(OH)2D3 modified at C-7, namely, 7-methyl-1α,25-(OH)2D3 (12) and 7-methyl-1α,25-(OH)2-19-nor-D3 (26), were synthesized biologically evaluated to gain further insights into structure-function relationships D. Key steps in synthesis 12 include functionalization C-7 by an efficient regioselective hydrostannylation allene precursor, construction triene framework a palladium-catalyzed intramolecular cyclization-Suzuki-Miyaura coupling cascade....
A homologous series of cholesterol-based liquid crystalline dimers were synthesized and characterized by polarizing optical microscopy, DSC, powder single-crystal XRD.
Vitamin D compounds possessing A rings prohibited from flipping to the alternative chair form (i.e., analogues 2 and 26) were synthesized. The bicyclic fragment 22 consisting of fused cyclohexane dihydropyran was constructed via ring-closing metathesis route. Also, a homologous synthon 23 with an attached ring successfully synthesized using this strategy. carbonyl deprotection in yielded cyclohexanone 5 that subjected Julia coupling anion phenylthiazoline sulfone 25. In resulting isomeric...
Six new analogues of 1α,25-dihydroxy-19-norvitamin D3 (3a–4b, 5, and 6) were prepared by a convergent synthesis applying the Wittig–Horner reaction as key step. The influence methyl groups at C-22 on their biological activity was examined. It established that both in vitro vivo is strongly dependent configuration stereogenic centers C-20 C-22. Introduction second group (analogues 5 generates compounds are slightly more potent than 1α,25-(OH)2D3 tests but much less vivo. greatest achieved...
As a continuation of our efforts directed to vitamin D compounds promising biological properties, 19-norvitamins 9-13, possessing 3'-hydroxypropylidene fragment attached C-2 and shortened 17β-alkyl chains, were synthesized. A new synthetic pathway providing the CD-ring ketones 20-24 is described starting from epimeric aldehydes 25 26. The hydrindanones subjected Wittig-Horner reaction with phosphine oxide 14, 9-13 obtained after hydroxyl deprotection. In comparison 1α,25-(OH)(2)D(3) (1),...
Continuing the structure-activity relationship studies in vitamin D area, we designed and synthesized novel C-9 substituted calcitriol analogues, possessing different nonpolar groups at this position. 9α-Methyl-1α,25-(OH)2D3, both epimers of 9-methylene-10,19-dihydro-1α,25-(OH)2D3 as well parent with "reversed" triene system, 9-methylene-19-nor-1α,25-(OH)2D3, were obtained from previtamin precursors, constructed by either Suzuki-Miyaura, Sonogashira, or Stille couplings corresponding A-...