58701-45-4

Usage

Uses

Protected Pregnenolone derivative.

Upstream product

• 145-13-1 Pregnenolone 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 421-83-0 trifluoromethane sulfonyl chloride 
• 57-88-5 cholesterol 
• 979-02-2 16-dehydropregnenolone acetate 
• 1778-02-5 Pregnenolone acetate 

Downstream Products

• 99602-21-8 (20(22)E,23E,25E)-26-phenyl-27-norcholesta-5,20-(22),23,25-tetraen-3β-ol 
• 99602-20-7 (20(22)E,23Z,25E)-26-phenyl-27-norcholesta-5,20-(22),23,25-tetraen-3β-ol 
• 137576-42-2 (R)-1-[(3S,8S,9S,10R,13S,14S,17S)-3-(tert-Butyl-dimethyl-silanyloxy)-10,13-dimethyl-7-phenylsulfanyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-ethanol 
• 137576-43-3 (R)-1-[(3S,8S,9S,10R,13S,14S,17S)-7-Benzenesulfinyl-3-(tert-butyl-dimethyl-silanyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-ethanol 
• 61574-54-7 pregnenolone-17α,21,21,21-d₄ 

Relevant academic research and scientific papers

Synthesis of the fatty sterol bound protein for a new sterol antibody

For the purpose of applying the particular antibodies as a new diagnostic procedure for atherosclerosis and related diseases, we successfully achieved the synthesis of the fatty sterol with a linker, then linked the target protein to this sterol. Synthesis was started from pregnenolone and achieved by the Grignard reaction with pentenyl magnesium bromide, regioselective photo-addition of thiolacetic acid toward the 25-double bond, esterification of 3-OH with linoleic anhydride, in situ conjunction of the cross-linker (MBS) to the thiol group after selective deprotection from its acetyl ester, and finally by the reaction with protein such as KLH or albumin through this linker. (C) 2000 Elsevier Science Ltd. All rights reserved.

ACETYLENIC CHOLESTERYL DERIVATIVES AS IRREVERSIBLE INHIBITORS OF ECDYSONE BIOSYNTHESIS

Two series of acetylenic derivatives of cholesterol were synthesized from stigmasterol and pregnenolone.These compounds carry an acetylenic function at C-22 and were devised with the aim to inhibit the C-22hydroxylation of ecdysone biosynthesis by a suicide-substrate mechanism.Two of these compounds (15a, 15f) inhibit the synthesis of ecdysone in follicular cells under in vitro conditions.The inhibition is selective of the C-22 hydroxylase system.

Synthesis of new C-25 and C-26 steroidal acids as potential ligands of the nuclear receptors DAF-12, LXR and GR

A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity.

STEREOSPECIFIC SYNTHESIS OF HYDROXYLATED STEROID SIDE CHAINS. SYNTHESIS OF 25,28-DIHYDROXY-7,8-DIHYDROERGOSTEROL AND ITS C-24 EPIMER VIA SIGMATROPIC REARRANGEMENT.

An efficient, stereospecific synthesis of hydroxylated ergosterol and C-24 epi-ergosterol side chains has been developed using a C-20 keto-steroid as starting material.The side chain is elaborated via stereoselective hydroboration, asymmetric reduction and a stereospecific sigmatropic rearrangement.

Synthesis of withanolide A, biological evaluation of its neuritogenic properties, and studies on secretase inhibition

Neurons on steroids: A stereoselective synthesis of the neuritogenic steroid lactone withanolide A was achieved by singlet oxygen ene reaction, Wharton transposition, a Corey-Seebach homologation, and a vinylogous aldol reaction. Biological evaluation demonstrated neurite outgrowth, which supports the potential neuritogenic role of this compound in traditional Indian medicine.

Identification of Inhibitors of Cholesterol Transport Proteins Through the Synthesis of a Diverse, Sterol-Inspired Compound Collection

Cholesterol transport proteins regulate a vast array of cellular processes including lipid metabolism, vesicular and non-vesicular trafficking, organelle contact sites, and autophagy. Despite their undoubted importance, the identification of selective modulators of this class of proteins has been challenging due to the structural similarities in the cholesterol-binding site. Herein we report a general strategy for the identification of selective inhibitors of cholesterol transport proteins via the synthesis of a diverse sterol-inspired compound collection. Fusion of a primary sterol fragment to an array of secondary privileged scaffolds led to the identification of potent and selective inhibitors of the cholesterol transport protein Aster-C, which displayed a surprising preference for the unnatural-sterol AB-ring stereochemistry and new inhibitors of Aster-A. We propose that this strategy can and should be applied to any therapeutically relevant sterol-binding protein.

Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement

Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and th

Smooth receptor ligand

The invention relates to the technical field of biology, particularly to a smooth receptor ligand, and provides a smooth receptor ligand or an isomer prodrug, a solvate and a pharmaceutically acceptable salt thereof, wherein the structural formula of the smooth receptor ligand is A-linker-B, A is an extracellular domain ligand structure, B is a transmembrane domain ligand structure, and Linker isa linear subunit inactive to the smooth receptor. According to the novel double-end small molecule ligand for the smooth receptor, by combining the crystal structure data of the smooth receptor, a linker is introduced into the proper sites of an extracellular domain ligand and a transmembrane domain ligand to obtain brand-new double-end ligand small molecules, so that the interaction between the ligand and the receptor and the biological activity of the ligand are enhanced.

OXYSTEROLS THAT ACTIVATE LIVER X RECEPTOR SIGNALING AND INHIBIT HEDGEHOG SIGNALING

This invention relates, e.g., to compositions comprising oxysterol compounds represented by Formula I or Formula II, e.g., comprising one or more of Oxy 16, Oxy 22, Oxy30, Oxy 31, Oxy35, Oxy37, Oxy43, Oxy44, Oxy45 or Oxy47. The compounds are shown to be Hedgehog pathway inhibiting, and to act as agonists for liver X receptor (LXR). Also disclosed are methods of using compositions of the invention to inhibit Hedgehog signaling effects, such as cell proliferation, including treating subjects in need thereof, and pharmaceutical compositions and kits for implementing methods of the invention.

Isotope-Labeling Studies Support the Electrophilic Compound i Iron Active Species, FeO3+, for the Carbon-Carbon Bond Cleavage Reaction of the Cholesterol Side-Chain Cleavage Enzyme, Cytochrome P450 11A1

The enzyme cytochrome P450 11A1 cleaves the C20-C22 carbon-carbon bond of cholesterol to form pregnenolone, the first 21-carbon precursor of all steroid hormones. Various reaction mechanisms are possible for the carbon-carbon bond cleavage step of P450 11A1, and most current proposals involve the oxoferryl active species, Compound I (FeO3+). Compound I can either (i) abstract an O-H hydrogen atom or (ii) be attacked by a nucleophilic hydroxy group of its substrate, 20R,22R-dihydroxycholesterol. The mechanism of this carbon-carbon bond cleavage step was tested using 18O-labeled molecular oxygen and purified P450 11A1. P450 11A1 was incubated with 20R,22R-dihydroxycholesterol in the presence of molecular oxygen (18O2), and coupled assays were used to trap the labile 18O atoms in the enzymatic products (i.e., isocaproaldehyde and pregnenolone). The resulting products were derivatized and the 18O content was analyzed by high-resolution mass spectrometry. P450 11A1 showed no incorporation of an 18O atom into either of its carbon-carbon bond cleavage products, pregnenolone and isocaproaldehyde. The positive control experiments established retention of the carbonyl oxygens in the enzymatic products during the trapping and derivatization processes. These results reveal a mechanism involving an electrophilic Compound I species that reacts with nucleophilic hydroxy groups in the 20R,22R-dihydroxycholesterol intermediate of the P450 11A1 reaction to produce the key steroid pregnenolone.