Efficient syntheses of 17-β-amino steroids

Taylor, Scott D.; Harris, Jesse

doi:10.1016/j.steroids.2011.04.013

Cited by 13 publications

(8 citation statements)

References 16 publications

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“…The amino derivative of estrone was synthesized by a two-step procedure reported by Taylor et al, which involved the reductive amination using STAB-H followed by hydrogenolysis using 10% Pd/C under an hydrogen atmosphere (Figure 1). 39 The 1 H NMR spectrum depicted the disappearance of the peaks of the aromatic protons of the benzyl group at 7.2−7.4 ppm and the methylene protons attached to the benzyl group at 3.8 ppm, after hydrogenolysis, thereby confirming the successful formation of the 17β-amino estrone (Supporting Information (SI) Figure S1). In addition, the base peak in LCMS revealed a value of 272.45 [M + H + ], which was close to the calculated value of 272.21 (SI, Figure S2).…”

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confidence: 99%

Estrone-Decorated Polyion Complex Micelles for Targeted Melittin Delivery to Hormone-Responsive Breast Cancer Cells

et al. 2020

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Tumor targeting has revolutionized cancer research, especially active cellular targeting of nanoparticles, where they are specifically homed to the pathological site to deliver the therapeutics. This strategy, which involves the utilization of affinity ligands on the surface of the nanocarriers, minimizes the nonspecific uptake of nanocarriers and the subsequent harmful side effects in healthy cells. Estrone, one of the mammalian estrogens, has affinity for estrogen receptors (ERα), which are overexpressed in hormone-responsive breast cancers. Despite holding promise, the potential of estrone in active targeting of nanoparticles has barely been explored. Herein, we developed an estrone-appended polyion complex (PIC) micelle to deliver melittin, a cytotoxic peptide, to breast cancer cells. Amino functionalization of estrone was performed to conjugate estrone to the diblock polymer synthesized by reversible addition–fragmentation chain-transfer (RAFT) polymerization. Estrone-conjugated poly(ethylene glycol) methyl ether methacrylate-b-poly tert-butyl methacrylate (POEGMEMA-P t BuMA) could complex with melittin to form PIC micelles of size around 60 nm ensuing from the electrostatic interaction of the deprotected polymer and melittin in aqueous media. Poly(ethylene glycol) methyl ether acrylate-b-poly acrylic acid (POEGMEA-PAA) was also later incorporated to afford PIC micelles that could exhibit similar cytotoxicity to free melittin in the cytotoxicity studies. The estrone-attached PIC micelles exhibited improved cytotoxicity in two-dimensional (2D) and three-dimensional (3D) cellular models of MCF-7 cells. Cross-linking of the PIC micelles was also performed to improve the stability of the micelles and prevent melittin degradation from enzymatic attack. Flow cytometry demonstrated an enhanced cellular uptake greater than sixfold with the estrone-conjugated PIC micelles, thereby establishing a profound difference in the targeting efficacy of the PIC micelles between MCF-7 and MDA-MB-231 cells. Furthermore, the distribution of the PIC micelles in the spheroids was revealed by light sheet microscopy. The results demonstrate the potential of estrone-anchored PIC micelles for targeted delivery of therapeutics to hormone-responsive breast cancer cells.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Estrone-Decorated Polyion Complex Micelles for Targeted Melittin Delivery to Hormone-Responsive Breast Cancer Cells

et al. 2020

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“…The structures of the synthesized compounds were proven using IR, PMR, 13 C NMR, and mass spectral data.Broad spectra of biological activity make steroids and their derivatives promising for discovering new efficacious drugs [1][2][3]. The high antibacterial, antiviral, and antitumor activity of hydrazono-, amino-, and amido-derivatives of the androstane, estrane, and cholestane series [4][5][6][7][8] and the expanded scope of their synthetic analogs helped to find new biological properties of these compounds.In continuation of research on the synthesis of bioactive 5D-steroids from epiandrosterone 1 [9, 10], a transformation product of tigogenin, hydrazones 2-4 were obtained.…”

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Synthesis and Antiviral Activity of Several N-Containing 5α-STEROIDS

et al. 2016

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A study of the antiviral activity of several new hydrazones and amines and amides of 5D-steroids that were synthesized by us earlier found highly and moderately active compounds. The structures of the synthesized compounds were proven using IR, PMR, 13 C NMR, and mass spectral data.Broad spectra of biological activity make steroids and their derivatives promising for discovering new efficacious drugs [1][2][3]. The high antibacterial, antiviral, and antitumor activity of hydrazono-, amino-, and amido-derivatives of the androstane, estrane, and cholestane series [4][5][6][7][8] and the expanded scope of their synthetic analogs helped to find new biological properties of these compounds.In continuation of research on the synthesis of bioactive 5D-steroids from epiandrosterone 1 [9, 10], a transformation product of tigogenin, hydrazones 2-4 were obtained.

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“…Saturated and unsaturated 17E-aminosteroids are used as intermediates to synthesize biologically active derivatives [5,6]. Peptide analogs of amidosteroids, among which compounds with various physiological activities such as anti-arrhythmic and antitumor have been found, were prepared by adding amino acids to aminosteroids [7,8].…”

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Synthesis from Tigogenin of 17β-Amino-5α-Androstan-3β-Ol Peptide Derivatives

et al. 2016

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New peptide derivatives of 17E-amino-5D-androstan-3E-ol were synthesized. Their structures were elucidated using PMR and 13 C NMR spectra and elemental analyses.Modification of steroids with pharmacophores in order to discover new highly active compounds is a critical problem [1][2][3][4]. Saturated and unsaturated 17E-aminosteroids are used as intermediates to synthesize biologically active derivatives [5,6]. Peptide analogs of amidosteroids, among which compounds with various physiological activities such as anti-arrhythmic and antitumor have been found, were prepared by adding amino acids to aminosteroids [7,8].Previously, we studied the possibility of producing peptide derivatives of 5D-steroidal oximes, intermediates in the transformation of tigogenin. New peptide analogs were prepared using the known method [9, 10] for synthesizing reagents, i.e., N-protected (D-aminoacyl)benzotriazoles, and O-acylation of 17-hydroximino-5D-androstanolone and 20-hydroximines of 3E-acetoxy-and 3E-hydroxy-5D-pregn-16-enolone [11].The goal of the present work was to study N-acylation of 17E-amino-5D-androstan-3E-ol (1) in order to synthesize biologically active amino derivatives. A similar modification of Amefalone (3D-amino-2E-hydroxy-5D-androstan-17-one), which possesses high anti-arrhythmic activity, decreased its toxicity [12]. Peptide derivatives 2-5 were synthesized after the optimum acylation conditions were developed. The reaction was carried out by refluxing mixtures of 1 and the corresponding reagents (N-Cbz-L-Ala-Bt; N-Cbz-L- Val-Bt, N-Cbz-L-Phe-Bt, and N-Cbz-L-Ala-L-Val-Bt) in anhydrous THF in the presence of TEA. Starting amine 1, which exhibited anti-arrhythmic activity [13], was prepared from tigogenin using the method developed by us [14].The structures of synthesized 2-5 were confirmed by PMR and 13 C NMR spectral data and elemental analyses. PMR spectra of 2-5 showed resonances for angular 18-CH 3 and 19-CH 3 as singlets at G 0.66-0.88 ppm. Multiplets for the 3D protons appeared at G 3.58 ppm; 17D-protons, G 3.77-3.90 ppm. Methyl resonances of the amino acids of 2 and 5 (alanine groups) appeared as doublets at G 1.37 ppm; of 3 (valine group), as a multiplet at G 0.95 ppm; of dipeptide 5 (valine

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Efficient syntheses of 17-β-amino steroids

Cited by 13 publications

References 16 publications

Estrone-Decorated Polyion Complex Micelles for Targeted Melittin Delivery to Hormone-Responsive Breast Cancer Cells

Estrone-Decorated Polyion Complex Micelles for Targeted Melittin Delivery to Hormone-Responsive Breast Cancer Cells

Synthesis and Antiviral Activity of Several N-Containing 5α-STEROIDS

Synthesis from Tigogenin of 17β-Amino-5α-Androstan-3β-Ol Peptide Derivatives

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