- Synthesis of side-chain oxysterols and their enantiomers through cross-metathesis reactions of Δ22 steroids
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A synthetic route that utilizes a cross-metathesis reaction with Δ22 steroids has been developed to prepare sterols with varying C-27 side-chains. Natural sterols containing hydroxyl groups at the 25 and (25R)-26 positions were prepared. Enantiomers of cholesterol and (3β,25R)-26-hydroxycholesterol (27-hydroxycholesterol) trideuterated at C-19 were prepared for future biological studies.
- Brownholland, David P.,Covey, Douglas F.
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- PEPTIDES
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The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.
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Page/Page column 25; 26
(2016/06/14)
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- Inhibitory effect of oxygenated cholestan-3-ol derivatives on the growth of Mycobacterium tuberculosis
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A variety of cholestan-3-ol derivatives, which are oxygenated at different positions of the steroid ring system, were prepared and tested for their inhibition of the Mycobacterium tuberculosis H37Rv strain. Several compounds showed significant antitubercular activities with MIC90 values in the range 4-8 μM and low or non-detectable toxicity against mammalian cells.
- Schmidt, Arndt W.,Choi, Taylor A.,Theumer, Gabriele,Franzblau, Scott G.,Kn?lker, Hans-Joachim
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p. 6111 - 6113
(2013/11/06)
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- Stereoselective synthesis and hormonal activity of novel dafachronic acids and naturally occurring steroids isolated from corals
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A stereoselective synthesis of (25S)-Δ1-, (25S)-Δ1,4-, (25S)-Δ1,7-, (25S)- Δ8(14)-, (25S)-Δ4,6,8(14)-dafachronic acid, methyl (25S)-Δ1,4-dafachronate and (25S)-5α-hydroxy-3,6- dioxocholest-7-en-26-oic acid is described. (25S)-Δ1,4- Dafachronic acid and its methyl ester are natural products isolated from corals and have been obtained by synthesis for the first time. (25S)-5α-Hydroxy- 3,6-dioxocholest-7-en-26-oic acid represents a promising synthetic precursor for cytotoxic marine steroids.
- Saini, Ratni,Boland, Sebastian,Kataeva, Olga,Schmidt, Arndt W.,Kurzchalia, Teymuras V.,Kn?lker, Hans-Joachim
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p. 4159 - 4163
(2012/07/14)
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- Synthesis and biological activity of the (25R)-cholesten-26-oic acids - Ligands for the hormonal receptor DAF-12 in Caenorhabditis elegans
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We describe the stereoselective transformation of diosgenin (4a) to (25R)-Δ4-dafachronic acid (1a), (25R)-Δ7- dafachronic acid (2a), and (25R)-cholestenoic acid (3a), which represent potential ligands for the hormonal receptor DAF-12
- Martin, Rene,Schmidt, Arndt W.,Theumer, Gabriele,Krause, Tilo,Entchev, Eugeni V.,Kurzchalia, Teymuras V.,Knoelker, Hans-Joachim
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experimental part
p. 909 - 920
(2009/05/30)
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- Synthesis and hormonal activity of the (25s)-cholesten-26-oic acids -potent ligands for the daf-12 receptor in caenorhabditis elegans
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Using a highly stereoselective Evans aldol reaction for the introduction of the stereogenic center at C-25, we describe an efficient synthesis of the orthogonally diprotected (25S)-26-hydroxycholesterol 11. In a few synthetic steps, this crucial intermediate 11 has been converted into the four (25S)-cholesten-26-oic acids 1-4, which have been obtained in 12-15 steps and 19-53% overall yield based on commercially available 3p-hydroxychol-5-en-24-oic acid (5). Our biological studies of the compounds 1-4 reveal that (25S)-Δ7-dafachronic acid (1) represents the most active steroidal ligand for the hormonal receptor DAF-12 in Caenorhabditis elegans. Moreover, the saturated (25S)-dafachronic acid (3) represents a new ligand for this receptor and the (25S)-steroidal acids are more active as compared to their corresponding (25R)-counterparts.
- Martin, Rene,Entchev, Eugeni V.,Daebritz, Frank,Kurzchalia, Teymuras V.,Knoelker, Hans-Joachim
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experimental part
p. 3703 - 3714
(2009/12/05)
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- Stereoselective synthesis of (25r)-dafachronic acids and (25R)-cholestenoic acid as potential ligands for the DAF-12 receptor in Caenorhabditis elegans
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Commercially available diosgenin has been used as starting material for a highly efficient synthesis of (25R)-dafachronic acids and (25R)-cholestenoic acid, potential ligands for the receptor DAF-12 in the nematode Caenorhabditis elegans.
- Martin, René,Schmidt, Arndt W.,Theumer, Gabriele,Kurzchalia, Teymuras V.,Kn?lker, Hans-Joachim
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scheme or table
p. 1965 - 1968
(2009/04/11)
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- Stereoselective synthesis of the hormonally active (25S)- Δ7-dafachronic acid, (25S)-Δ4-dafachronic acid, (25S)-dafachronic acid, and (25S)-cholestenoic acid
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We report a stereoselective synthesis of the (25S)-cholestenoic-26-acids which are highly efficient ligands for the hormonal receptor DAF-12 in Caenorhabditis elegans.
- Martin, Rene,Daebritz, Frank,Entchev, Eugeni V.,Kurzchalia, Teymuras V.,Knoelker, Hans-Joachim
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scheme or table
p. 4293 - 4295
(2009/02/07)
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- Synthesis of the aglycone of the shark repellent pavoninin-4 using remote functionalization
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The aglycone of shark repellent pavoninin-4, (25R)-5α-cholestan- 3α,15α,26-triol 26-acetate 1a, was synthesized from (25R)-cholest-5-en-3β,-26-diol 4 (26-hydroxycholesterol) in eight steps in 18% overall yield. Breslow's remote functionalization strategy
- Gong, Hua,Williams, John R.
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p. 2253 - 2255
(2007/10/03)
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- Preparation of (25R)- and (25S)-26-functionalized steroids as tools for biosynthetic studies of cholic acids
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A new synthesis of both epimeric forms of 26-cholestanoic acids and 26-alcohols containing a 3β-hydroxy-Δ5- or a Δ4-3-keto-functionality in ring A is described starting from stigmasterol or (20S)-3β-acetoxy-pregn-5-en-20-carboxylic a
- Khripach, Vladimir A.,Zhabinskii, Vladimir N.,Konstantinova, Olga V.,Khripach, Natalya B.,Antonchick, Alexey V.,Antonchick, Andrey P.,Schneider, Bernd
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p. 551 - 562
(2007/10/03)
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- Clemmensen reduction of diosgenin and kryptogenin: Synthesis of [16,16,22,22,23,23-2H6]-(25R)-26-hydroxycholesterol
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A new experimental protocol has been established for the Clemmensen reduction of diosgenin and kryptogenin with the aim to prepare deuterated isotopomers of (25R)-26-hydroxycholesterol. Uncontrolled deuteration has been achieved from diosgenin, whereas [16,16,22,22,23,23-2H 6]-(25R)-26-hydroxycholesterol (1) can be synthesized from kryptogenin.
- Alessandrini, Laura,Ciuffreda, Pierangela,Santaniello, Enzo,Terraneo, Giancarlo
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p. 789 - 794
(2007/10/03)
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- Oxysterols: 27-hydroxycholesterol and its radiolabeled analog
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We describe a convenient and stereoselective route to the synthesis of 27-hydroxycholesterol. Also its radiolabeled analog, 22, 23 di [3H]-27-hydroxycholesterol with high specific radioactivity (55 Ci/mmol) was synthesized by this method. Julia
- D'Ambra, Thomas E.,Javitt, Norman B.,Lacy, James,Srinivasan, Puliyur,Warchol, Tadeusz
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p. 401 - 407
(2007/10/03)
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- Lipase-catalyzed resolution of stereogenic centers in steroid side chains by transesterification in organic solvents: The case of a 26- hydroxycholesterol
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The Pseudomonas cepacia (PCL) lipase selectively catalyzes the acylation of the (25S)-isomer of the (25R,S)-26-hydroxycholesterol 1a when the transesterification is irreversibly carried out with vinyl acetate in a mixture of organic solvents (chloroform/t
- Ferraboschi, Patrizia,Rezaelahi, Shahrzad,Verza, Elisa,Santaniello, Enzo
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p. 2193 - 2196
(2007/10/03)
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- Synthesis of (25R)-cholest-5-ene-3β,26-diol and its radiolabeled analog
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A new, convenient and stereoselective route to the synthesis of (25R)-cholest-5-ene-3β,26-diol (1) and its radiolabeled analog 4 is described. The key step is a Julia condensation of sulfone 6 with aldehyde 12 to furnish compound 13. Further reduction of
- D'Ambra, Thomas E.,Javitt, Norman B.,Nakanishi, Koji,Warchol, Tadeusz
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p. 3801 - 3804
(2007/10/03)
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- SYNTHESIS OF (25R)-CHOLESTEROL AND 1H N.M.R. AND H.P.L.C. RESOLUTION OF (25R)- AND (25S)-26-HYDROXYCHOLESTEROL
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Yamogenin acetate (1) was isolated from crude diosgenin acetate and converted into (25S)-26-hydroxycholesterol (6a).The absolute configuration at C-25 of (6a) was determined by X-ray crystallography. (25R)-Cholesterol (10) was prepared by reduction of the 26-tosyloxy group by LiAl(2)H4.Reverse-phase h.p.l.c. resolution without derivatization was developed for the diastereoisomers, (25R)- and (25S)-26-hydroxycholesterol.The (+)- or (-)-MTPA esters of these diastereoisomers showed distinctive 1H n.m.r. signals for 26-H.
- Uomori, Atsuko,Seo, Shujiro,Sato, Tomohiro,Yoshimura, Yohko,Takeda, Ken'ichi
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p. 1713 - 1718
(2007/10/02)
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- Biohydrogenation of Unsaturated Compounds by Saccharomyces cerevisiae. Part 2. (S)-(-)-Ethyl 4-Hydroxy-3-methylbutenoate as a Chiral Synthon for the Preparation of (25S)-26-Hydroxycholesterol
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(25S)-26-Hydroxycholesterol (1b) has been synthesized from stigmasterol (4a) and (S)-(-)-ethyl 4-hydroxy-3-methylbutanoate (2a), the latter having the necessary chirality for the synthesis of the steroidal side-chain.
- Ferraboschi, Patrizia,Fiecchi, Alberto,Grisenti, Paride,Santaniello, Enzo
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p. 1749 - 1752
(2007/10/02)
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- Synthesis of (25S)-2H1>Cholesterol and 1H N.m.r. Signal Assignments of the pro-R and pro-S Methyl Groups at C-25
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(25S)-2H1>Cholesterol (11) has been prepared from diosgenin (1), and the absolute configuration at C-25 of the crucial intermediate , (25R)-26-hydroxycholesterol (6), has been identified by X-ray crystallographic analysis.The two methyl groups at C-25 of cholesterol have been examined by 1H n.m.r. spectroscopy and the two sets of doublet methyl signals due to 27-H and 26-H have been observed at δH 0.862 and 0.866 downfield from the internal reference.The former was assigned to 27-H, the pro-R methyl group attached at C-25, and the latter to 26-H, the pro-S methyl group attached at C-25.The 13C n.m.r. signal assignments of the methyl groups at C-25 reported by Popjak were confirmed on the basis of the signals of the deuteriated cholesterol (11).
- Shujiro, Seo,Yohko, Yoshimura,Tomohiro, Satoh,Atsuko, Uomori,Ken'ichi, Takeda
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p. 411 - 414
(2007/10/02)
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- STEREOSPECIFIC SYNTHESIS OF (25R)-26-HYDROXYCHOLESTEROL VIA SIGMATROPIC REARRANGEMENT. A NEW STEREOSELECTIVE TWO-CARBON HOMOLOGATION OF 20-KETO STEROIDS TO THE 23-ALDEHYDE.
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Pregnenolone was stereoselectively converted into (25R)-26-hydroxycholesterol using a stereoselective hydroboration, assymetric reduction and a strereospecific sigmatropic rearrangement as key steps.
- Midland, M. Mark,Kwon, Young C.
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p. 5021 - 5024
(2007/10/02)
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- Synthesis of (20R,25R)-Cholest-5-ene-3β,26-diol and the Occurence of Base-Catalyzed 1,5-Hydride Shift in a Steroidal 1,5-Ketol
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Details are presented for the preparation of (20R,25R)-cholest-5-ene-3β,26-diol (2, "26-hydroxycholesterol").Kryptogenin diacetate (8) was converted to 2 in 39percent yield by successive removal of the C-16 and C-22 carbonyl functions (cycloethylene dithioketal formation followed by Raney nickel desulfurization). 22-Oxocholest-5-ene-3β,26-diol (17) was shown to be an intermediate in a previous preparation of 2, and it was shown to be a source of C-25 epimerization and byproducts in that procedure.The products seen in the Wolf-Kishner reduction of 17 are explained by base-catalyzed equalibration of 17 with 26-xocholest-5-ene-3β,22-diol (23).This equilibration by base-catalysed 1,5-hydride shift was demonstrated by deuterium labelling. 13C and 1H NMR correlations were developed for the above compounds.
- Kluge, Arthur F.,Maddox, Michael L.,Partidge, Leslie G.
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p. 2359 - 2365
(2007/10/02)
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- CONVERSION OF RUSCOGENIN INTO 1α- AND 1β-HYDROXYCHOLESTEROL DERIVATIVES STRUCTURE ELUCIDATION BY COMPUTER ASSISTED ANALYSIS OF THEIR LANTHANIDE-INDUCED NMR SHIFTS
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The chemistry of ruscogenin (1) was studied since its structural features qualify it to serve as a potential starting material for 1-hydroxy vitamin D analogs.Ruscogenin was oxidized to the 1-oxo-derivative 2 which was reduced to a mixture of ruscogenin (1) and 1-epiruscogenin (3).Both 1 and 3 were converted by Clemmensen reduction to the respective tetrols 12 and 21, which were further reduced to the triols 15 and 25 and diols 16 and 24 by consecutive treatment with p-toluenesulfonylchloride and LAH.The reduction of triol 15 to diol 20 was achieved by selective benzoylation of positions 1 and 3, and mesylation of position 16 followed by LAH reduction.The utility of the shift reagent Eu(dpm)3 to determine the structures of the products was studied.It was shown that the shifts induced are characteristic of the position and orientation of the OH groups, and can facilitate the elucidation of the structures of hydroxylated steroids.
- Noam, M.,Tamir. I.,Breuer, E.,Mechoulam, R.
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p. 597 - 604
(2007/10/02)
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- On the C-25 Chirality of 26-Hydroxycholesterol
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The stereospecific synthesis of (25S)-26-hydroxycholesterol with a chiral synthon derived from (S)-(+)-3-hydroxy-2-methylpropanoic acid is described and the Cotton effects of the CD spectra were found not to be a general means for distinguishing epimers of monohydric secondary alcohols or for distinguishing epimers in which the chiral center is in the α position to the primary alcoholic function.
- Byon, Chang-Yon,Gut, Marcel,Toome, Voldemar
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p. 3901 - 3903
(2007/10/02)
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