Improved protocols for the selective deprotection of trialkylsilyl ethers using fluorosilicic acid

Pilcher, Anthony S.; DeShong, Philip

doi:10.1021/jo00071a023

Cited by 57 publications

(36 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The silyl ether protective group in 5 was cleaved with aqueous fluorosilicic acid 25 and the resulting triol 6 was oxidized with pyridinium dichromate (PDC) and the tertiary hydroxyl groups protected as trimethylsilyl ethers. Wittig-Horner reactions of the resulting ketone 7 with 8, 9, and 10, followed by treatments with tetrabutylammonium fluoride, gave 11, 12, and 13, respectively, as illustrated in Scheme 2.…”

Section: Synthesismentioning

confidence: 99%

Calcitriol derivatives with two different side-chains at C-20. Part 4: Further chain modifications that alter VDR-dependent monocytic differentiation potency in human leukemia cells

Garay

Jankowski

Lizano

et al. 2007

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Signaling of cell differentiation is one of the important physiological functions of the activated vitamin D receptor (VDR). Activation of the VDR can be achieved not only by 1α,25-dihydroxyvitamin D 3 (1,25D), the natural ligand, but also by a large number of its analogs. These include a category containing two side chains emanating at C-20, generally referred to as Gemini. The introduction of a cyclopropyl moiety as part of the pro-R side chain provides modified Gemini compounds with increased steric requirement and decreased chain flexibility; the biological consequences of this novel structural variant are subject of this investigation. In general, the resulting 1α,25-dihydroxy-(4-hydroxy-4-methyl-pentyl)-21,22-cis-cyclo-cholecalciferols reduced had differentiation and transcriptional potency and induced cell cycle arrest less effciently, as shown by a decrease in G1/S ratio, when compared to 1,25D. Modifying their calcitriol side chain in the form of a 4-hydroxy-4-trifluoromethyl-5,5,5-trifluoropent-2-ynyl moiety, however, resulted in pronounced induction of differentiation in 1,25D-sensitive and moderate level of differentiation in 1,25D-resistant leukemia cells.

show abstract

Section: Synthesismentioning

confidence: 99%

Calcitriol derivatives with two different side-chains at C-20. Part 4: Further chain modifications that alter VDR-dependent monocytic differentiation potency in human leukemia cells

Garay

Jankowski

Lizano

et al. 2007

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Addition of hexafluoroacetone furnished the side chain construct as depicted in 20a and in the target compounds 6a and 6b. The two silyl ether protective groups in 20a were cleaved simultaneously with aqueous fluorosilicic acid [22,23] in acetonitrile to give the corresponding triol 20b. Subsequent oxidation with pyridinium dichromate furnished ketone 21a.…”

Section: Introductionmentioning

confidence: 99%

Formal Desymmetrization of the Diastereotopic Chains in Gemini Calcitriol Derivatives with Two Different Side Chains at C‐20

Maehr

Uskoković

2004

Eur J Org Chem

View full text Add to dashboard Cite

Derivatives of calcitriol with two equal side chains emanating at C‐20, also known as gemini, have emerged as interesting compounds, either as instruments for assessing the steric requirements of the vitamin D receptor or as drug candidates. We now describe the syntheses of gemini analogs where the two side chains differ from each other. While retaining the 2‐hydroxy‐2‐methylpentyl moiety, common to both calcitriol and gemini, as one chain, we replaced the other with a 1,1,1‐trifluoro‐2‐hydroxy‐2‐(trifluoromethyl)‐3‐pentynyl group. The features comprising this chain modification are commonly regarded to improve toxicity profiles and drug performance. The resulting epimeric pairs with a new stereogenic center at C‐20 were resolved and the absolute configurations assigned. The side‐chain desymmetrization protocols described herein serve as a basis for additional synthesis activity in this area. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

show abstract

“…16 Later studies (Scheme 3) proved, that using H2SiF6 in a sub-stoichiometric manner provide selective removal of TBDMS over TIPS from benzyl-ethers. 17…”

Section: Scheme 2 Catalytic Protodesilylation Strategiesmentioning

confidence: 99%

“…: 143 -144 °C), Rf (Hex.-EtOAc = 5:1) = 0.60; 1 H NMR (250 MHz, CDCl3) δ = 7.70 (td, J = 10, 2.5 Hz, 2H), 7.49 -7.37 (m, 3H), 7.21 -7.06 (m, 2H), 6.88 (td, J = 32, 2.0 Hz, 2H), 6.78 (d, J = 0.8 Hz, 1H), 3.75 (s, 3H) ppm. 13 5-(1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl (14), 147(10), 136(15), 121 (36), 120 (28), 115 (26), 106 (18), 102 (12), 90 (30), 89(44), 88 (24), 78(40), 73 (30), 63 (17), 51(10). IR (thin film, ATR): 1607, 1568, 1519, 1346, 1230, 1072, 1048, 859, 783, 746, 688 cm -1 .…”

Section: -(4-methoxyphenyl)benzofuran 5 4amentioning

confidence: 99%

Catalytic Activation of Trimethylsilylacetylenes: A One-Pot Route to Unsymmetrical Acetylenes and Heterocycles

et al. 2018

View full text Add to dashboard Cite

For the synthesis of unsymmetrical acetylenes, a Sonogashira coupling-deprotection-Sonogashira coupling reaction sequence is often used. Removal of protecting groups requires harsh conditions or an excess of difficult to handle and expensive reagents. Herein, we disclose a novel catalytic method for the selective deprotection of trimethylsilylacetylenes in Sonogashira reaction. The reagent hexafluorosilicic acid, an inexpensive nontoxic compound, was used to promote the selective desilylation. This method enables the efficient synthesis of unsymmetric acetylenes with other silylated functional groups present. Further possibilities of the method were explored by synthesis of heterocycles.

show abstract

Improved protocols for the selective deprotection of trialkylsilyl ethers using fluorosilicic acid

Cited by 57 publications

References 0 publications

Calcitriol derivatives with two different side-chains at C-20. Part 4: Further chain modifications that alter VDR-dependent monocytic differentiation potency in human leukemia cells

Calcitriol derivatives with two different side-chains at C-20. Part 4: Further chain modifications that alter VDR-dependent monocytic differentiation potency in human leukemia cells

Formal Desymmetrization of the Diastereotopic Chains in Gemini Calcitriol Derivatives with Two Different Side Chains at C‐20

Catalytic Activation of Trimethylsilylacetylenes: A One-Pot Route to Unsymmetrical Acetylenes and Heterocycles

Contact Info

Product

Resources

About