Synthesis of bilin‐1,19‐diones and biladiene‐<i>ac</i>‐1,19‐diones with c(10) adamantyl and <i>tert</i>‐butyl groups

Kar, A.; Lightner, David A.

doi:10.1002/jhet.5570350404

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…The resulting yellow oil was purified by flash column chromatography (silica, 95% hexanes, 5% EtOAc) to afford the aldehyde as a white powder (0.59 g, 3.56 mmol) in 59% yield. 1 H NMR (400 MHz, CD 2 Cl 2 ): δ 9.29 (s, 1H, C H O), 2.05 (br m, 3H, β-C H ), 1.77 (br m, 6H, α-C H 2 ), 1.70 (br m, 6H, δ-C H 2 ); lit . δ 9.32 (s, 1H), 2.06 (m, 3H), 1.73 (m, 12H).…”

Section: Methodsmentioning

confidence: 99%

Alkylation of Iridium via Tandem Carbon−Hydrogen Bond Activation/Decarbonylation of Aldehydes. Access to Complexes with Tertiary and Highly Hindered Metal−Carbon Bonds

2000

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Reactions between Cp*(PMe 3 )Ir(Me)OTf (1) and aldehydes (RCHO) proceed with high selectivity to give the hydrocarbyl carbonyl salts [Cp*(PMe 3 )Ir(R)(CO)][OTf] (R ) Me (2), Et (3), n-Pr (4), c-Pr (5), Ph (6), 1-ethylpropyl (7), p-tolyl (8), mesityl (9), 2-(Z)-1-phenylpropenyl (10), vinyl (13), t-Bu (14), 1-adamantyl ( 17)). This tandem C-H bond activation/decarbonylation reaction provides access to the first isolated tertiary alkyl complexes of iridium. X-ray diffraction studies were performed on mesityl complex 9, tert-butyl derivative 15, and 1-adamantyl compound 18. Decarbonylation of cyclopropyl complex 5 results in irreversible opening of the cyclopropyl ring. This reaction has provided useful information concerning the mechanism of C-H activation of cyclopropane by 1. Hydride reduction of the p-tolyl carbonyl salt 8 has provided an example of a rare transition-metal formyl complex, Cp*-(PMe 3 )Ir(p-tolyl)(CHO) (28).

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Section: Methodsmentioning

confidence: 99%

Alkylation of Iridium via Tandem Carbon−Hydrogen Bond Activation/Decarbonylation of Aldehydes. Access to Complexes with Tertiary and Highly Hindered Metal−Carbon Bonds

2000

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“…All carbonyl compounds were commercially available except 1-adamantane carboxaldehyde and 1-adamantane acetaldehyde, which were synthesized from corresponding alcohols by Swern oxidation. 10 The synthetic procedure is available as Supplementary Data. After completion of this step, the “catch and release” procedure was repeated to remove the excess of carbonyl compounds (Fig.…”

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confidence: 99%

Identification of SQ609 as a lead compound from a library of dipiperidines

Bogatcheva

Hanrahan

Никоненко

et al. 2011

Bioorganic & Medicinal Chemistry Letters

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We recently reported that compounds created around a dipiperidine scaffold demonstrated activity against Mycobacterium tuberculosis (Mtb) (Bogatcheva, E.; Hanrahan, C.; Chen, P.; Gearhart, J.; Sacksteder, K.; Einck, L.; Nacy, C.; Protopopova, M. Bioorg. Med. Chem. Lett.2010, 20, 201). To optimize the dipiperidine compound series and to select a lead compound to advance into preclinical studies, we evaluated the structure-activity relationship (SAR) of our proprietary libraries. The (piperidin-4-ylmethyl)piperidine scaffold was an essential structural element required for antibacterial activity. Based on SAR, we synthesized a focused library of 313 new dipiperidines to delineate additional structural features responsible for antitubercular activity. Thirty new active compounds with MIC 10-20μg/ml on Mtb were identified, but none was better than the original hits of this series, SQ609, SQ614, and SQ615. In Mtb-infected macrophages in vitro, SQ609 and SQ614 inhibited more than 90% of intracellular bacterial growth at 4μg/ml; SQ615 was toxic to these cells. In mice infected with Mtb, weight loss was completely prevented by SQ609, but not SQ614, and SQ609 had a prolonged therapeutic effect, extended by 10-15days, after cessation of therapy. Based on in vitro and in vivo antitubercular activity, SQ609 was identified as the best-in-class dipiperidine compound in the series.

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“…There is no reason to think that the structure of the analogous mesobiliverdin-XIIIα dimethyl ester would differ much [6]. However, coloraltering distortions of the verdin structure have been engineered into the skeleton by synthesis: a tert-butyl group at C(10) opens the verdin helix to give red compounds with the ~640 nm long wavelength λ max shifted to 490-543 nm [7,8], and a stilbene belt connecting the two lactams that forces the pigment to adopt a porphyrin-like conformation and exhibit a blue color (λ max 608 nm) when cis-stilbene and a stretched shape with a magenta color (λ max 559 nm), when trans-stilbene [9]. The pigment color-conformation relationship is consistent with that observed for 1, where conformational change is induced by protonation and detected unequivocally by nOe experiments.…”

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confidence: 99%

N₂₁,N₂₂-carbonyl-bridged biliverdin. red-blue color change effected by conformation

Boiadjiev

Lightner

2005

Journal of Heterocyclic Chemistry

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An N 21 ,N 22 -carbonyl-bridged mesobiliverdin, prepared in high yield by reaction of the unbridged parent (λ max 639 nm, ε 15,700, chloroform) with 1,1 '-carbonyldiimidazole and 1,8-diazabicyclo[5.4.0]undec-7-ene, gave magenta-colored solutions in chloroform that absorb strongly in the visible spectrum (λ max 534 nm, ε 27,700) and shifted to bright blue (λ max 669 nm, ε 35,300) upon addition of trifluoroacetic acid.J. Heterocyclic Chem., 42, 161 (2005).Reaction of dipyrrinones, such as methyl xanthobilirubinate (Scheme 1A) with 1,1'-carbonyldiimidazole (CDI) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) has been shown to give the N,N'-carbonyl-bridged dipyrrinones in excellent yield [1]. The latter are highly fluorescent (φ F~0 .7-0.8) [2] but the long wavelength absorption λ max (428 nm, chloroform) shows a 20 nm bathochromic shift from that of the parent (λ max 406 nm, chloroform) [1,3]. A similar reaction with blue-colored (λ max 639 nm, chloroform) mesobiliverdin-XIIIα dimethyl ester (Scheme 1B) afforded the N 21 ,N 22 -bridged verdin (1) in 76% yield. The new "verdin" was neither blue nor green, but exhibited an intense magenta color in chloroform solution (λ max 534 nm) associated with a strong hypsochromic shift relative to the parent. It was also non-fluorescent to the eye. The absence of visible fluorescence at room temperature was confirmed by instrumental measurements in chloroform and trifluoroacetic acid following independent excitation of the three uv-visible absorption bands.The structure of 1 follows from that of its symmetric verdin precursor [4]. The 13 C-nmr (Table 1) (Table 1), due to a rapid prototropic shift, N 22 -H to N 23 , tautomerism.) The 13 C nmr assignments and structure were further confirmed by long range heteronuclear correlation experiment (gHMBC). In particular, the hydrogen at C(5) appeared deshielded to 6.49 ppm as it does in xanthoglow methyl ester (Scheme 1A) and is correlated ( 2 J) to the carbon signals at 132.5 ppm C(4) and 130.2 ppm C(6) and ( 3 J) to C(3) at 146.6 ppm and C(7) at 123.0 ppm. In the opposite half of the molecule, the hydrogen at C(15) is with normal chemical shift at 5.84 ppm and correlated to C(13), C(14), C(16) and C(17). The 2 J correlation C(15)-H to C(14) and the unique 3 J correlation C(13 1 )-CH 3 to C(14) is interesting because it reveals that C(14) is strongly deshielded (to 169.7 ppm) relative to C(6) (130.2 ppm). The carbon and proton nmr spectral data are thus consistent with structure 1 for the new bridged verdin.A striking color change, from magenta to bright blue was seen when solutions of 1 were exposed to acid, e.g., chloroform and dimethyl-sulfoxide solutions plus trifluoroacetic acid. The color change is readily measured spectrophotometrically, as seen in the uv-visible spectra of 1 (Figure 1) in a variety of solvents, although solvents such as tetrahydrofuran, dimethylformamide and dimethylsulfoxide require larger excess of trifluoroacetic acid than do benzene, chloroform, etc. No similar large wavelength changes are det...

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Synthesis of bilin‐1,19‐diones and biladiene‐ac‐1,19‐diones with c(10) adamantyl and tert‐butyl groups

Cited by 8 publications

References 24 publications

Alkylation of Iridium via Tandem Carbon−Hydrogen Bond Activation/Decarbonylation of Aldehydes. Access to Complexes with Tertiary and Highly Hindered Metal−Carbon Bonds

Alkylation of Iridium via Tandem Carbon−Hydrogen Bond Activation/Decarbonylation of Aldehydes. Access to Complexes with Tertiary and Highly Hindered Metal−Carbon Bonds

Identification of SQ609 as a lead compound from a library of dipiperidines

N₂₁,N₂₂-carbonyl-bridged biliverdin. red-blue color change effected by conformation

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Synthesis of bilin‐1,19‐diones and biladiene‐ac‐1,19‐diones with c(10) adamantyl and tert‐butyl groups

Cited by 8 publications

References 24 publications

Alkylation of Iridium via Tandem Carbon−Hydrogen Bond Activation/Decarbonylation of Aldehydes. Access to Complexes with Tertiary and Highly Hindered Metal−Carbon Bonds

Alkylation of Iridium via Tandem Carbon−Hydrogen Bond Activation/Decarbonylation of Aldehydes. Access to Complexes with Tertiary and Highly Hindered Metal−Carbon Bonds

Identification of SQ609 as a lead compound from a library of dipiperidines

N21,N22-carbonyl-bridged biliverdin. red-blue color change effected by conformation

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N₂₁,N₂₂-carbonyl-bridged biliverdin. red-blue color change effected by conformation